bluuebunny/crossref_metadata_2025 huggingface dataset:
Indoor and Outdoor Particulate Matter Concentrations at Schools in the Athens Area
Authors: Diapouli E. , Chaloulakou A. , Spyrellis N.
Published: January 2007

Simultaneous indoor and outdoor PM10 and PM2.5 concentration measurements were conducted in seven primary schools in the Athens area during the winter of 2003-04 and 2004-05. The measurements were performed during school hours with the use of Harvard PEMs. Indoor PM10 and PM2.5 concentrations were also monitored continuously by a DustTrak monitor. Mean PM10 concentration was 236.13μg·m-3 indoors and 162.89μg·m-3 outdoors. The corresponding mean values for PM2.5 were 82.65μg·m-3 indoors and 56.25μg·m-3 outdoors. Indoor/Outdoor (I/O) ratios were close or above 1.00 at almost all sites. Indoor PM levels were greatly influenced by the presence of people and intensity of indoor activities. Moreover, PM concentrations exhibited significant short-term variability, underlying the need to include short-term measurements in children’s exposure studies.
Exposure to Mites, Sensitisation and Allergy to Mites in Moisture Damaged Buildings
Authors: Pennanen S. , Mussalo-Rauhamaa H. , Harju A. , Pippuri M. , Liesivuori J. , Elg P. , Hakala K. , Haahtela T.
Published: January 2007

We assessed the mite exposure of patients in the Skin and Allergy Hospital by collecting samples of settled dust from their workplaces and homes. Mites were counted and identified microscopically. Mites were found in 26% of the samples. Three samples (3%) contained more than 100 mites per gram dust and another sample (1%) had more than 500 mites per gram dust, the suggested limits for mite sensitisation and at which acute allergic symptoms can be expected, respectively. Mites were a more common finding from water damaged houses and workplaces with visible mould but they also existed in large numbers in buildings with no reported indoor air quality problems. Dust mites ( Pyroglyphidae) were the most abundant species. However, storage mites were also frequently found. Patients reported a high prevalence of respiratory symptoms, especially nose and eye irritation which may partly be due to sensitisation especially to storage mites. Although mites are commonly found in workplaces and homes they are seldom present in high concentrations. Mite sensitisation and especially a positive reaction to storage mites in skin prick tests may be an indication of a moisture problem in the domestic or work environments.
The oxidative stress response regulates DKK1 expression through the JNK signaling cascade in multiple myeloma plasma cells
Authors: Colla Simona , Zhan Fenghuang , Xiong Wei , Wu Xiaosong , Xu Hongwei , Stephens Owen , Yaccoby Shmuel , Epstein Joshua , Barlogie Bart , Shaughnessy John D.
Published: January 2007

Multiple myeloma (MM) plasma cells, but not those from healthy donors and patients with monoclonal gammopathy of undetermined significance or other plasma cell dyscrasias involving the bone marrow, express the Wnt-signaling antagonist DKK1. We previously reported that secretion of DKK1 by MM cells likely contributes to osteolytic lesions in this disease by inhibiting Wnt signaling, which is essential for osteoblast differentiation and survival. The mechanisms responsible for activation and regulation of DKK1 expression in MM are not known. Herein, we could trace DKK1 expression changes in MM cells to perturbations in the JNK signaling cascade, which is differentially modulated through oxidative stress and interactions between MM cells with osteoclasts in vitro. Despite its role as a tumor suppressor and mediator of apoptosis in other cell types including osteoblasts, our data suggest that DKK1, a stress-responsive gene in MM, does not mediate apoptotic signaling, is not activated by TP53, and its forced overexpression could not inhibit cell growth or sensitize MM cells to apoptosis following treatment with thalidomide or lenalidomide. We conclude that specific strategies to modulate persistent activation of the JNK pathway may be beneficial in preventing disease progression and treating myeloma-associated bone disease by inhibiting DKK1 expression.
Talc mediates angiostasis in malignant pleural effusionsviaendostatin induction
Authors: Najmunnisa N. , Mohammed K. A. , Brown S. , Su Y. , Sriram P. S. , Moudgil B. , Loddenkemper R. , Antony V. B.
Published: January 2007

Talc remains the most effective sclerosing agent for pleurodesis. However, its mechanism of action in resolving pleural malignant disease remains unclear.

The present study evaluated the angiogenic balance in the pleural space in patients with malignant pleural effusions (MPE) following talc insufflation.

Patient pleural fluid samples were collected both before and after talc insufflation. The ability of pleural mesothelial cells (PMC) and malignant mesothelioma cells (MMC) to produce endostatinin vitrowas compared. The biological effects of pleural fluids and conditioned media from talc-activated PMC on endothelial cells were evaluated by performing proliferation, invasion, tube formation and apoptosis assays.

Pleural fluids from patients with MPE who received thoracoscopic talc insufflation contained significantly higher levels of endostatin (median 16.75 ng·mL−1) compared with pre-talc instillation (1.06 ng·mL−1). Talc-activated PMC released significantly greater amounts of endostatin (mean±sem1052.39±38.66 pg·mL−1) when compared with a MMC line (134.73±8.72 pg·mL−1).

In conlusion, talc alters the angiogenic balance in the pleural space from a biologically active and angiogenic environment to an angiostatic milieu. Functional improvement following talc poudrage in patients with malignant pleural effusions may, in part, reflect these alterations in the pleural space.
Increased galectin-3 expression and intra-epithelial neutrophils in small airways in severe COPD
Authors: Pilette C. , Colinet B. , Kiss R. , André S. , Kaltner H. , Gabius H-J. , Delos M. , Vaerman J-P. , Decramer M. , Sibille Y.
Published: January 2007

Galectins-1 and -3 regulate epithelial proliferation/apoptosis and neutrophil activation, and are implicated in lung cancer and asthma. The role of galectins in chronic obstructive pulmonary disease (COPD), characterised by epithelial changes and neutrophil infiltration, remains unknown.

In the present study, galectin-1 and -3 expression was assessed by immunohistology in the bronchial epithelium of lung specimens from eight severe COPD patients and compared with nine nonsmokers and six smokers without COPD. Findings were related to epithelial proliferation (Ki-67), tissue inflammation and lung function.

Epithelial galectin-3 immunostaining was increased only in the small airways of COPD patients when compared with nonsmokers and smokers. In contrast, galectin-1 was only significantly increased in the small airways of the group of smokers. Ki-67+ epithelial cells and neutrophils were increased in the small airways of COPD patients when compared with smokers. Furthermore, intra-epithelial neutrophils correlated in the small airways with Ki-67+ epithelial cells and with the forced expiratory volume in one second/forced vital capacity ratio. However, no correlation was observed with galectin expression.

The present study supports the hypothesis that distal airways represent an important site for detecting changes in chronic obstructive pulmonary disease. In patients with severe disease, an increased galectin-3 expression and neutrophil accumulation in the small airway epithelium was demonstrated, correlating with epithelial proliferation and airway obstruction.
The role of nebulised budesonide in the treatment of exacerbations of COPD
Authors: Gunen H. , Hacievliyagil S. S. , Yetkin O. , Gulbas G. , Mutlu L. C. , In E.
Published: January 2007

The present study was designed to evaluate the hypothesis that nebulised budesonide (NB) might be an alternative to systemic corticosteroids (SC) in the treatment of patients with exacerbations of chronic obstructive pulmonary disease (ECOPD).

Patients hospitalised with ECOPD (n = 159) were randomised into three groups. Group 1 received only standard bronchodilator treatment (SBDT), group 2 received SC (40 mg prednisolone) plus SBDT, and group 3 received NB (1,500 μgq.i.d.) plus SBDT. Improvement during 10-day hospitalisation was compared with exacerbation and rehospitalisation rates after discharge.

While mean±sdage was 64.1±8.9 yrs (female/male = 0.1), mean forced expiratory volume in one second (FEV1) at admission was found to be 37.2±12.2% predicted. Arterial blood gases and spirograms recovered faster in groups 2 and 3. While improvements in arterial oxygen tension (Pa,O2) and forced vital capacity (FVC) in group 2, and improvements inPa,O2, FVC and FEV1in group 3, became significant at 24-h control, the first significant improvement in group 1 appeared in arterial oxygen saturation at 72-h control. The mean improvement ofPa,O2after 10 days was 1.20 and 1.06 kPa (9 and 8 mmHg) higher in group 2 and 3, respectively, than in group 1. Blood glucose exhibited an upward trend only in group 2.

The study demonstrates that nebulised budesonide may be an effective and safe alternative to systemic corticosteroids in the treatment of exacerbations of chronic obstructive pulmonary disease.
Childhood adiposity predicts adult-onset current asthma in females: a 25-yr prospective study
Authors: Burgess J. A. , Walters E. H. , Byrnes G. B. , Giles G. G. , Jenkins M. A. , Abramson M. J. , Hopper J. L. , Dharmage S. C.
Published: January 2007

Few data exist on associations between childhood adiposity and incident asthma in later life. The present authors examined the relationship between childhood body mass index (BMI) and incident asthma beginning in adolescence or in adult life.

All subjects included in the study were participants in the Tasmanian Asthma Survey, a large population-based cohort study, and were asthma free at 7 yrs of age. Weight, height and lung function were measured at 7 yrs of age. Asthma status at 7 and 32 yrs of age was ascertained by questionnaire. Odds ratios were calculated for the association between childhood adiposity, expressed as “overweight” or as BMI z-score quartiles at 7 yrs of age, and asthma development after that age.

In females, but not in males, there was a significant association between adiposity at 7 yrs of age and current asthma at 32 yrs of age that developed after the age of 21 yrs. The association was not explained by childhood lung function or age at menarche. There was no association between adiposity at 7 yrs of age and asthma that developed after that age and remitted at 32 yrs of age in either sex.

Higher body mass index in nonasthmatic young females at 7 yrs of age predicts risk of current asthma developing in adult life.
Air pollution and development of asthma, allergy and infections in a birth cohort
Authors: Brauer M. , Hoek G. , Smit H. A. , de Jongste J. C. , Gerritsen J. , Postma D. S. , Kerkhof M. , Brunekreef B.
Published: January 2007

Few studies have addressed associations between traffic-related air pollution and respiratory disease in young children. The present authors assessed the development of asthmatic/allergic symptoms and respiratory infections during the first 4 yrs of life in a birth cohort study (n = ∼4,000).

Outdoor concentrations of traffic-related air pollutants (nitrogen dioxide PM2.5, particles with a 50% cut-off aerodynamic diameter of 2.5 μm and soot) were assigned to birthplace home addresses with a land-use regression model. They were linked by logistic regression to questionnaire data on doctor-diagnosed asthma, bronchitis, influenza and eczema and to self-reported wheeze, dry night-time cough, ear/nose/throat infections and skin rash. Total and specific immunoglobulin (Ig)E to common allergens were measured in a subgroup (n = 713).

Adjusted odds ratios (95% confidence intervals) per interquartile pollution range were elevated for wheeze (1.2 (1.0–1.4) for soot), doctor-diagnosed asthma (1.3 (1.0–1.7)), ear/nose/throat infections (1.2 (1.0–1.3)) and flu/serious colds (1.2 (1.0–1.4)). No consistent associations were observed for other end-points. Positive associations between air pollution and specific sensitisation to common food allergens (1.6 (1.2–2.2) for soot), but not total IgE, were found in the subgroup with IgE measurements.

Traffic-related pollution was associated with respiratory infections and some measures of asthma and allergy during the first 4 yrs of life.
Automatic detection of sleep-disordered breathing from a single-channel airflow record
Authors: Nakano H. , Tanigawa T. , Furukawa T. , Nishima S.
Published: January 2007

Single-channel airflow monitors developed for screening of sleep-disordered breathing (SDB) have conflicting results for accuracy. It was hypothesised that the analytical algorithm is crucial for the performance and the present authors tried to develop a novel computer algorithm.

A total of 399 polysomnography (PSG) records were employed, including a thermal sensor signal. The first 100 records were used in the development of the algorithm and the remainder for validation. In addition, 119 PSG records, including a thermocouple signal and a nasal pressure signal, were used for the validation. The algorithm was designed to obtain a time series (flow-power) using power spectral analysis, which expresses fluctuation in the airflow signal amplitude. From the time series the algorithm detects transient falls of the flow-power and calculates flow-respiratory disturbance index (RDI), defined as the number of falls per hour.

In the validation group, the areas under receiver operating characteristic curves for diagnosis of SDB (apnoea/hypopnoea index ≥5) were 0.96, 0.95 and 0.95, for the records of the thermal sensor, thermocouple and nasal pressure system, respectively. The diagnostic sensitivity/specificity ratios of the flow-RDI were 96/76, 88/80 and 97%/77%, respectively.

The present results suggest that a single-channel airflow monitor can be used to detect sleep-disordered breathing automatically if the analytic algorithm is optimised.
Haemoglobin level and its clinical impact in a cohort of patients with COPD
Authors: Cote C. , Zilberberg M. D. , Mody S. H. , Dordelly L. J. , Celli B.
Published: January 2007

Haemoglobin (Hb) abnormalities in chronic obstructive pulmonary disease (COPD) are not well characterised. The present authors investigated the prevalence and association of abnormal Hb with clinical outcomes.

Analysis of a prospective cohort of stable COPD outpatients (n = 683) in a USA Veterans Administration pulmonary clinic was undertaken. Patients were classified as anaemic (Hb <13 g·dL−1), polycythemic (Hb ≥17 g·dL−1and ≥15 g·dL−1for males and females, respectively) or normal. Demographic characteristics and physiological/functional outcomes were compared between groups. Regression models adjusting for confounders examined the independent association of anaemia with clinical outcomes.

Anaemia was present in 116 (17%) patients and polycythemia in 40 (6%). While the only values that differed between polycythemic and nonpolycythemic patients were mean body mass index and Hb, anaemic patients showed a significantly higher modified Medical Research Council dyspnoea scale score (2.8versus2.6), lower 6-min walk distance (265versus325 m) and shorter median survival (49versus74 months) than nonanaemic patients. In regression models, anaemia independently predicted dyspnoea and reduced exercise capacity.

Anaemia in chronic obstructive pulmonary disease was an independent risk factor for reduced functional capacity. Polycythemia prevalence was low and had no association with worsened outcomes. Further work is required to evaluate the effect of anaemia correction on outcomes in chronic obstructive pulmonary disease.
Calcitonin gene-related peptide relates to cough sensitivity in children with chronic cough
Authors: Chang A. B. , Gibson P. G. , Ardill J. , McGarvey L. P. A.
Published: January 2007

Airway neuropeptides, in particular calcitonin gene-related peptide (CGRP), are likely to be important in the pathogenesis of chronic cough. The present authors evaluated the following: 1) the relationship between cough sensitivity and bronchoalveolar lavage (BAL) neuropeptides; and 2) the effect of reflux oesophagitis (RO) on cough, cough sensitivity and BAL neuropeptides in children not selected for cough. It was hypothesised that CGRP would be increased in children with chronic cough and would relate to cough sensitivity.

Capsaicin cough sensitivity was performed in children undergoing gastro-duodenal endoscopy. CGRP, substance P and neurokinin A were measured in BAL obtained nonbronchoscopically. Children were defined as “coughers” if chronic cough was present.

Coughers (n = 21) had significantly reduced cough sensitivity but were just as likely as noncoughers (n = 19) to have RO. The median CGRP was significantly higher in coughers with oesophagitis than in noncoughers with oesophagitis. CGRP significantly negatively correlated to cough sensitivity in coughers but not in noncoughers.

Elevated calcitonin gene-related peptide, but not substance P or neurokinin A, is only associated with chronic cough in children when oesophagitis coexists. Calcitonin gene-related peptide in bronchoalveolar lavage relates to cough sensitivity and is likely to be important in the pathophysiology of chronic cough.
Reticulate phylogeny of gastropod-shell-breeding cichlids from Lake Tanganyika – the result of repeated introgressive hybridization
Authors: Koblmüller Stephan , Duftner Nina , Sefc Kristina M , Aibara Mitsuto , Stipacek Martina , Blanc Michel , Egger Bernd , Sturmbauer Christian
Published: January 2007

Background

The tribe Lamprologini is the major substrate breeding lineage of Lake Tanganyika's cichlid species flock. Among several different life history strategies found in lamprologines, the adaptation to live and breed in empty gastropod shells is probably the most peculiar. Although shell-breeding arose several times in the evolutionary history of the lamprologines, all obligatory and most facultative shell-breeders belong to the so called "ossified group", a monophyletic lineage within the lamprologine cichlids. Since their distinctive life style enables these species to live and breed in closest vicinity, we hypothesized that these cichlids might be particularly prone to accidental hybridization, and that introgression might have affected the evolutionary history of this cichlid lineage.

Results

Our analyses revealed discrepancies between phylogenetic hypotheses based on mitochondrial and nuclear (AFLP) data. While the nuclear phylogeny was congruent with morphological, behavioral and ecological characteristics, several species – usually highly specialized shell-breeders – were placed at contradicting positions in the mitochondrial phylogeny. The discordant phylogenies strongly suggest repeated incidents of introgressive hybridization between several distantly related shell-breeding species, which reticulated the phylogeny of this group of cichlids. Long interior branches and high bootstrap support for many interior nodes in the mitochondrial phylogeny argue against a major effect of ancient incomplete lineage sorting on the phylogenetic reconstruction. Moreover, we provide morphological and genetic (mtDNA and microsatellites) evidence for ongoing hybridization among distantly related shell-breeders. In these cases, the territorial males of the inferred paternal species are too large to enter the shells of their mate, such that they have to release their sperm over the entrance of the shell to fertilize the eggs. With sperm dispersal by water currents and wave action, trans-specific fertilization of clutches in neighboring shells seem inevitable, when post-zygotic isolation is incomplete.

Conclusion

From the direct observation of hybrids we conclude that hybridization between distantly related gastropod-shell-breeding cichlids of Lake Tanganyika follows inevitably from their ecological specialization. Moreover, the observed incongruence between mtDNA and nuclear multilocus phylogeny suggests that repeated hybridization events among quite distantly related taxa affected the diversification of this group, and introduced reticulation into their phylogeny.
GO-2D: identifying 2-dimensional cellular-localized functional modules in Gene Ontology
Authors: Zhu Jing , Wang Jing , Guo Zheng , Zhang Min , Yang Da , Li Yanhui , Wang Dong , Xiao Guohua
Published: January 2007

Background

Rapid progress in high-throughput biotechnologies (e.g. microarrays) and exponential accumulation of gene functional knowledge make it promising for systematic understanding of complex human diseases at functional modules level. Based on Gene Ontology, a large number of automatic tools have been developed for the functional analysis and biological interpretation of the high-throughput microarray data.

Results

Different from the existing tools such as Onto-Express and FatiGO, we develop a tool named GO-2D for identifying 2-dimensional functional modules based on combined GO categories. For example, it refines biological process categories by sorting their genes into different cellular component categories, and then extracts those combined categories enriched with the interesting genes (e.g., the differentially expressed genes) for identifying the cellular-localized functional modules. Applications of GO-2D to the analyses of two human cancer datasets show that very specific disease-relevant processes can be identified by using cellular location information.

Conclusion

For studying complex human diseases, GO-2D can extract functionally compact and detailed modules such as the cellular-localized ones, characterizing disease-relevant modules in terms of both biological processes and cellular locations. The application results clearly demonstrate that 2-dimensional approach complementary to current 1-dimensional approach is powerful for finding modules highly relevant to diseases.
GSTT2 promoter polymorphisms and colorectal cancer risk
Authors: Jang Sang-Geun , Kim Il-Jin , Kang Hio Chung , Park Hye-Won , Ahn Sun-A , Yoon Hyun-Ju , Kim Kun , Shin Hai-Rim , Lee Jin Soo , Park Jae-Gahb
Published: January 2007

Background

Glutathione S-transferases are a group of enzymes that participate in detoxification and defense mechanisms against toxic carcinogens and other compounds. These enzymes play an important role in human carcinogenesis. In the present study, we sought to determine whether GSTT2 promoter single nucleotide polymorphisms (SNPs) are associated with colorectal cancer risk.

Methods

A total of 436 colorectal cancer patients and 568 healthy controls were genotyped for three GSTT2 promoter SNPs (-537G>A, -277T>C and -158G>A), using real-time TaqMan assay and direct sequencing. An electrophoretic mobility shift assay (EMSA) was performed to determine the effects of polymorphisms on protein binding to the GSTT2 promoter.

Results

The -537A allele (-537G/A or A/A) was significantly associated with colorectal cancer risk (OR = 1.373, p = 0.025), while the -158A allele (-158G/A or A/A) was involved in protection against colorectal cancer (OR = 0.539, p = 0.032). Haplotype 2 (-537A, -277T, -158G) was significantly associated with colorectal cancer risk (OR = 1.386, p = 0.021), while haplotype 4 (-537G, -277C, -158A) protected against colorectal cancer (OR = 0.539, p = 0.032). EMSA data revealed lower promoter binding activity in the -537A allele than its -537G counterpart.

Conclusion

Our results collectively suggest that SNPs and haplotypes of the GSTT2 promoter region are associated with colorectal cancer risk in the Korean population.
Anti-proliferative activity of the quassinoid NBT-272 in childhood medulloblastoma cells
Authors: von Bueren André O , Shalaby Tarek , Rajtarova Julia , Stearns Duncan , Eberhart Charles G , Helson Lawrence , Arcaro Alexandre , Grotzer Michael A
Published: January 2007

Background

With current treatment strategies, nearly half of all medulloblastoma (MB) patients die from progressive tumors. Accordingly, the identification of novel therapeutic strategies remains a major goal. Deregulation of c-MYC is evident in numerous human cancers. In MB, over-expression of c-MYC has been shown to correlate with anaplasia and unfavorable prognosis. In neuroblastoma – an embryonal tumor with biological similarities to MB – the quassinoid NBT-272 has been demonstrated to inhibit cellular proliferation and to down-regulate c-MYC protein expression.

Methods

To study MB cell responses to NBT-272 and their dependence on the level of c-MYC expression, DAOY (wild-type, empty vector transfected or c-MYC transfected), D341 (c-MYC amplification) and D425 (c-MYC amplification) human MB cells were used. The cells were treated with different concentrations of NBT-272 and the impact on cell proliferation, apoptosis and c-MYC expression was analyzed.

Results

NBT-272 treatment resulted in a dose-dependent inhibition of cellular proliferation (IC50 in the range of 1.7 – 9.6 ng/ml) and in a dose-dependent increase in apoptotic cell death in all human MB cell lines tested. Treatment with NBT-272 resulted in up to 90% down-regulation of c-MYC protein, as demonstrated by Western blot analysis, and in a significant inhibition of c-MYC binding activity. Anti-proliferative effects were slightly more prominent in D341 and D425 human MB cells with c-MYC amplification and slightly more pronounced in c-MYC over-expressing DAOY cells compared to DAOY wild-type cells. Moreover, treatment of synchronized cells by NBT-272 induced a marked cell arrest at the G1/S boundary.

Conclusion

In human MB cells, NBT-272 treatment inhibits cellular proliferation at nanomolar concentrations, blocks cell cycle progression, induces apoptosis, and down-regulates the expression of the oncogene c-MYC. Thus, NBT-272 may represent a novel drug candidate to inhibit proliferation of human MB cells in vivo.
A perspective on microarrays: current applications, pitfalls, and potential uses
Authors: Jaluria Pratik , Konstantopoulos Konstantinos , Betenbaugh Michael , Shiloach Joseph
Published: January 2007

With advances in robotics, computational capabilities, and the fabrication of high quality glass slides coinciding with increased genomic information being available on public databases, microarray technology is increasingly being used in laboratories around the world. In fact, fields as varied as: toxicology, evolutionary biology, drug development and production, disease characterization, diagnostics development, cellular physiology and stress responses, and forensics have benefiting from its use. However, for many researchers not familiar with microarrays, current articles and reviews often address neither the fundamental principles behind the technology nor the proper designing of experiments. Although, microarray technology is relatively simple, conceptually, its practice does require careful planning and detailed understanding of the limitations inherently present. Without these considerations, it can be exceedingly difficult to ascertain valuable information from microarray data. Therefore, this text aims to outline key features in microarray technology, paying particular attention to current applications as outlined in recent publications, experimental design, statistical methods, and potential uses. Furthermore, this review is not meant to be comprehensive, but rather substantive; highlighting important concepts and detailing steps necessary to conduct and interpret microarray experiments. Collectively, the information included in this text will highlight the versatility of microarray technology and provide a glimpse of what the future may hold.
A randomised cross-over trial in healthy adults indicating improved absorption of omega-3 fatty acids by pre-emulsification
Authors: Garaiova Iveta , Guschina Irina A , Plummer Sue F , Tang James , Wang Duolao , Plummer Nigel T
Published: January 2007

Background

The health benefits of increased intakes of omega-3 fatty acids are well established but palatability often presents a problem. The process of emulsification is used in the food industry to provide a wider spectrum of use, often with the result of increased consumption. Moreover, as emulsification is an important step in the digestion and absorption of fats, the pre-emulsification process may enhance digestion and absorption. In this study the levels of plasma fatty acid and triacylglycerol (TAG) following the ingestion of either an oil mixture or an emulsified oil mixture have been compared.

Methods

In this randomised cross-over study, 13 volunteers received the oil mixture and 11 received the oil emulsion as part of an otherwise fat free meal. Blood samples were collected at 0, 1.5, 3, 4.5, 6, 7.5 and 9 hours after ingestion of oil, separated and stored at -20°C. Plasma triacylglycerols were assessed spectrophotometrically and fatty acids were determined by gas chromatography. Following a washout period of twenty days the procedure was repeated with the assignments reversed.

Results

The postprandial plasma TAG and the C18:3 (n-6), C18:3(n-3), C20:5(n-3) and C22:6 (n-3) polyunsaturated fatty acid (PUFA) levels for the emulsified oil group were increased significantly (P = 0.0182; P = 0.0493; P = 0.0137; P < 0.0001; P = 0.0355 respectively) compared with the non-emulsified oil group. The C16:0 and C18:0 saturated fatty acids, the C18:1 (n-9) monounsaturated fatty acid and the C18:2 PUFA were not significantly different for the oil and emulsified oil groups.

Conclusion

Pre-emulsification of an oil mixture prior to ingestion increases the absorption of longer chain more highly unsaturated fatty acids (especially eicosapentaenoic acid and docosahexaenoic acid) but does not affect absorption of shorter chain less saturated fatty acids, suggesting that pre-emulsification of fish oils may be a useful means of boosting absorption of these beneficial fatty acids.

Trial registration: Current Controlled Trials ISRCTN43202606
Identification of candidate methylation-responsive genes in ovarian cancer
Authors: Menendez Laura , Walker DeEtte , Matyunina Lilya V , Dickerson Erin B , Bowen Nathan J , Polavarapu Nalini , Benigno Benedict B , McDonald John F
Published: January 2007

Background

Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs) are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers.

Results

In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3) before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC). An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified.

Conclusion

We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.
Therapeutic use of Aldara™ in chronic myeloid leukemia
Authors: Marleau Annette M , Lipton Jeffrey H , Riordan Neil H , Ichim Thomas E
Published: January 2007

The potent clinical responses seen in patients with chronic myeloid leukemia (CML) after administration of donor-specific lymphocytes, as well as the correlation between the presence of antigen specific T cells and prolonged remission in these patients, suggests a role for the immunological control of CML. Here we propose Aldara™, a clinically used formulation of imiquimod, as an agent for augmenting immune responses to CML antigens. Our proposition is based upon 3 tenets: 1) Endogenous dendritic cells (DC) of CML patients, which are known to be derived from the malignant clone, express and present various leukemic antigens; 2) CML-antigen reactive T cell clones exist in the patient but in many situations are ineffectively stimulated to cause significant hematological responses; and 3) Antigen presentation by mature, activated DC, which endogenously express CML-antigens may endow the pre-existing ineffective T cell responses with ability to control CML progression. The practical use of Aldara™ as a localized activator of DC in the context of present day leukemic therapeutics, as well as various properties of this unique immune modulator will be discussed.
Retroviral activation of the mir-106a microRNA cistron in T lymphoma
Authors: Lum Amy M , Wang Bruce B , Li Lauri , Channa Namitha , Bartha Gabor , Wabl Matthias
Published: January 2007

Retroviral insertion into a host genome is a powerful tool not only for the discovery of cancer genes, but also for the discovery of potential oncogenic noncoding RNAs. In a large-scale mouse T lymphocyte tumor screen we found a high density of integrations upstream of the mir-106a microRNA cistron. In tumors containing an integration, the primary transcript encoding the mir-106a cistron was overexpressed five to 20-fold compared with that of control tumors; concomitantly, the mature mir-106a and mir-363 microRNAs were highly overexpressed as well. These findings suggest the mir-106a cistron plays an important role in T cell tumorigenesis.
Demonstration of infectious salmon anaemia virus (ISAV) endocytosis in erythrocytes of Atlantic salmon
Authors: Workenhe Samuel T , Wadowska Dorota W , Wright Glenda M , Kibenge Molly JT , Kibenge Frederick SB
Published: January 2007

Infectious salmon anaemia (ISA) virus (ISAV) is a fish orthomyxovirus that has recently been assigned to the new genus Isavirus within the family Orthomyxoviridae. It possesses the major functional characteristics of the virus family including haemagglutinating, receptor destroying enzyme (RDE), and fusion activities associated with the virion surface proteins. It is generally accepted that ISAV agglutinates erythrocytes of several fish species and that the ISAV RDE activity dissolves this haemagglutination reaction except for Atlantic salmon (Salmo salar) erythrocytes. We used electron microscopy to examine the physical interaction between ISAV and erythrocytes from Atlantic salmon and rainbow trout (Oncorhynchus mykiss) during haemagglutination. We present evidence that ISAV enters into Atlantic salmon erythrocytes. Atlantic salmon erythrocytes incubated with ISAV for 4 hours showed endocytosis of the virus particles, which is consistent with virus infection. These observations suggest that the lack of dissolution of ISAV-induced haemagglutination of Atlantic salmon erythrocytes favours virus infection of the erythrocytes. Moreover, such a haemagglutination-infection phenotype is fundamentally different from haemagglutination by avian and mammalian orthomyxoviruses, and is indicative of a different pathogenesis for the fish orthomyxovirus.
A novel superfamily containing the β-grasp fold involved in binding diverse soluble ligands
Authors: Burroughs A Maxwell , Balaji S , Iyer Lakshminarayan M , Aravind L
Published: January 2007

Background

Domains containing the β-grasp fold are utilized in a great diversity of physiological functions but their role, if any, in soluble or small molecule ligand recognition is poorly studied.

Results

Using sensitive sequence and structure similarity searches we identify a novel superfamily containing the β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins transcobalamin and intrinsic factor, the bacterial polysaccharide export proteins, the competence DNA receptor ComEA, the cob(I)alamin generating enzyme PduS and the Nqo1 subunit of the respiratory electron transport chain. We present evidence that members of this superfamily are likely to bind a range of soluble ligands, including B12. There are two major clades within this superfamily, namely the transcobalamin-like clade and the Nqo1-like clade. The former clade is typified by an insert of a β-hairpin after the helix of the β-grasp fold, whereas the latter clade is characterized by an insert between strands 4 and 5 of the core fold.

Conclusion

Members of both clades within this superfamily are predicted to interact with ligands in a similar spatial location, with their specific inserts playing a role in the process. Both clades are widely represented in bacteria suggesting that this superfamily was derived early in bacterial evolution. The animal lineage appears to have acquired the transcobalamin-like proteins from low GC Gram-positive bacteria, and this might be correlated with the emergence of the ability to utilize B12 produced by gut bacteria.

Reviewers

This article was reviewed by Andrei Osterman, Igor Zhulin, and Arcady Mushegian.
Neurotrophin/Trk receptor signaling mediates C/EBPα, -β and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription
Authors: Calella Anna Maria , Nerlov Claus , Lopez Rodolphe G , Sciarretta Carla , von Bohlen und Halbach Oliver , Bereshchenko Oksana , Minichiello Liliana
Published: January 2007

Background

Extracellular signaling through receptors for neurotrophins mediates diverse neuronal functions, including survival, migration and differentiation in the central nervous system, but the transcriptional targets and regulators that mediate these diverse neurotrophin functions are not well understood.

Results

We have identified the immediate-early (IE) genes Fos, Egr1 and Egr2 as transcriptional targets of brain derived neurotrophic factor (BDNF)/TrkB signaling in primary cortical neurons, and show that the Fos serum response element area responds to BDNF/TrkB in a manner dependent on a combined C/EBP-Ebox element. The Egr1 and Egr2 promoters contain homologous regulatory elements. We found that C/EBPα/β and NeuroD formed complexes in vitro and in vivo, and were recruited to all three homologous promoter regions. C/EBPα and NeuroD co-operatively activated the Fos promoter in transfection assays. Genetic depletion of Trk receptors led to impaired recruitment of C/EBPs and NeuroD in vivo, and elimination of Cebpa and Cebpb alleles reduced BDNF induction of Fos, Egr1 and Egr2 in primary neurons. Finally, defective differentiation of cortical dendrites, as measured by MAP2 staining, was observed in both compound Cebp and Ntrk knockout mice.

Conclusion

We here identify three IE genes as targets for BDNF/TrkB signaling, show that C/EBPα and -β are recruited along with NeuroD to target promoters, and that C/EBPs are essential mediators of Trk signaling in cortical neurons. We show also that C/EBPs and Trks are required for cortical dendrite differentiation, consistent with Trks regulating dendritic differentiation via a C/EBP-dependent mechanism. Finally, this study indicates that BDNF induction of IE genes important for neuronal function depends on transcription factors (C/EBP, NeuroD) up-regulated during neuronal development, thereby coupling the functional competence of the neuronal cells to their differentiation.
Fibroblast-like synovial cells from normal and inflamed knee joints differently affect the expression of pain-related receptors in sensory neurones: a co-culture study
Authors: von Banchet Gisela Segond , Richter Jonny , Hückel Marion , Rose Christina , Bräuer Rolf , Schaible Hans-Georg
Published: January 2007

Innervation of the joint with thinly myelinated and unmyelinated sensory nerve fibres is crucial for the occurrence of joint pain. During inflammation in the joint, sensory fibres show changes in the expression of receptors that are important for the activation and sensitization of the neurones and the generation of joint pain. We recently reported that both neurokinin 1 receptors and bradykinin 2 receptors are upregulated in dorsal root ganglion (DRG) neurones (the cell bodies of sensory fibres) in the course of acute and chronic antigen-induced arthritis in the rat. In this study, we begin to address mechanisms of the interaction between fibroblast-like synovial (FLS) cells and sensory neurones by establishing a co-culture system of FLS cells and DRG neurones. The proportion of DRG neurones expressing neurokinin 1 receptor-like immunoreactivity was not altered in the co-culture with FLS cells from normal joints but was significantly upregulated using FLS cells from knee joints of rats with antigen-induced arthritis. The proportion of DRG neurones expressing bradykinin 2 receptors was slightly upregulated in the presence of FLS cells from normal joints but upregulation was more pronounced in DRG neurones co-cultured with FLS cells from acutely inflamed joints. In addition, the expression of the transient receptor potential V1 (TRPV1) receptor, which is involved in inflammation-evoked thermal hyperalgesia, was mainly upregulated by co-culturing DRG neurones with FLS cells from chronically inflamed joints. Upregulation of neurokinin 1 receptors but not of bradykinin 2 and TRPV1 receptors was also observed when only the supernatant of FLS cells from acutely inflamed joint was added to DRG neurones. Addition of indomethacin to co-cultures inhibited the effect of FLS cells from acutely inflamed joints on neurokinin 1 receptor expression, suggesting an important role for prostaglandins. Collectively, these data show that FLS cells are able to induce an upregulation of pain-related receptors in sensory neurones and, thus, they could contribute to the generation of joint pain. Importantly, the influence of FLS cells on DRG neurones is dependent on their state of activity, and soluble factors as well as direct cellular contacts are crucial for their interaction with neurones.
Risk of second primary cancer in men with breast cancer
Authors: Satram-Hoang Sacha , Ziogas Argyrios , Anton-Culver Hoda
Published: January 2007

Introduction

A retrospective registry-based cohort study was conducted to examine the risk of second primary cancer following the occurrence of breast cancer in males.

Methods

Data obtained from the California Cancer Registry in the period 1988 to 2003 included 1,926 men aged 85 years and younger diagnosed with a first primary breast cancer. Person-year analysis was applied to determine the risk of second primary cancers after the occurrence of a first primary breast cancer. The effects of age, race, and time since the first breast cancer diagnosis were assessed.

Results

Of the 1,926 male breast cancer cases, 221 (11.5%) developed a second primary cancer. Men with first incidence of breast cancer have a significantly higher risk of second cancer (standardized incidence ratio (SIR) = 1.16, 95% confidence interval (CI) = 1.01–1.32). The risk of a second site-specific cancer is elevated for breast cancer (SIR = 52.12, 95% CI = 31.83–80.49), cutaneous melanoma (SIR = 2.98, 95% CI = 1.63–5.00) and stomach cancer (SIR = 2.11, 95% CI = 1.01–3.88). There is a general tendency towards higher risks of second malignancies among younger men compared to older men and the risk increased with the passage of time.

Conclusion

Male breast cancer patients should be monitored carefully for the occurrence of second primary cancers, especially a second primary breast cancer.
Liver dysfunction associated with artificial nutrition in critically ill patients
Authors: Grau Teodoro , Bonet Alfonso , Rubio Mercedes , Mateo Dolores , Farré Mercé , Acosta José Antonio , Blesa Antonio , Montejo Juan Carlos , de Lorenzo Abelardo García , Mesejo Alfonso ,   the Working Group on Nutrition and Metabolism of the Spanish Society of Critical Care
Published: January 2007

Introduction

Liver dysfunction associated with artificial nutrition in critically ill patients is a complication that seems to be frequent, but it has not been assessed previously in a large cohort of critically ill patients.

Methods

We conducted a prospective cohort study of incidence in 40 intensive care units. Different liver dysfunction patterns were defined: (a) cholestasis: alkaline phosphatase of more than 280 IU/l, gamma-glutamyl-transferase of more than 50 IU/l, or bilirubin of more than 1.2 mg/dl; (b) liver necrosis: aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l, plus bilirubin of more than 1.2 mg/dl or international normalized ratio of more than 1.4; and (c) mixed pattern: alkaline phosphatase of more than 280 IU/l or gamma-glutamyl-transferase of more than 50 IU/l, plus aspartate aminotransferase of more than 40 IU/l or alanine aminotransferase of more than 42 IU/l.

Results

Seven hundred and twenty-five of 3,409 patients received artificial nutrition: 303 received total parenteral nutrition (TPN) and 422 received enteral nutrition (EN). Twenty-three percent of patients developed liver dysfunction: 30% in the TPN group and 18% in the EN group. The univariate analysis showed an association between liver dysfunction and TPN (p < 0.001), Multiple Organ Dysfunction Score on admission (p < 0.001), sepsis (p < 0.001), early use of artificial nutrition (p < 0.03), and malnutrition (p < 0.01). In the multivariate analysis, liver dysfunction was associated with TPN (p < 0.001), sepsis (p < 0.02), early use of artificial nutrition (p < 0.03), and calculated energy requirements of more than 25 kcal/kg per day (p < 0.05).

Conclusion

TPN, sepsis, and excessive calculated energy requirements appear as risk factors for developing liver dysfunction. Septic critically ill patients should not be fed with excessive caloric amounts, particularly when TPN is employed. Administering artificial nutrition in the first 24 hours after admission seems to have a protective effect.
The struggle for iron: gastrointestinal microbes modulate the host immune response during infection
Authors: Markel Troy A , Crisostomo Paul R , Wang Meijing , Herring Christine M , Meldrum Kirstan K , Lillemoe Keith D , Meldrum Daniel R
Published: January 2007

The gastrointestinal track is one source of potential bacterial entry into the host, and the local immune system at the mucosal border is paramount in establishing host immune tolerance and the immune response to invading organisms. Macrophages use iron for production of hydroxy-radical and superoxide reactions, which are necessary for microbial killing. Presumably, as a survival strategy, bacteria, which also require iron for survival, have adapted the ability to sequester iron from the host, thereby limiting the availability to macrophages. As current modes of antimicrobial therapy are evolving, examination of nontraditional therapies is emerging. One such potential therapy involves altering the bacterial micronutrient iron concentration. Necrotizing enterocolitis is a clinical condition where such a strategy makes intuitive sense. This review will describe the immune response to gastrointestinal infection, the mechanisms that the gastrointestinal system uses to absorb intraluminal iron, and the critical role iron plays in the infectious process.
Growth from two transient apical initials in the meristem ofSelaginella kraussiana
Authors: Harrison C. Jill , Rezvani Mohi , Langdale Jane A.
Published: January 2007

A major transition in land plant evolution was from growth in water to growth on land. This transition necessitated major morphological innovations that were accompanied by the development of three-dimensional apical growth. In extant land plants, shoot growth occurs from groups of cells at the apex known as meristems. In different land plant lineages, meristems function in different ways to produce distinct plant morphologies, yet our understanding of the developmental basis of meristem function is limited to the most recently diverged angiosperms. To redress this balance, we have examined meristem function in the lycophyte Selaginella kraussiana. Using a clonal analysis, we show that S. kraussiana shoots are derived from the activity of two short-lived apical initials that facilitate the formation of four axes of symmetry in the shoot. Leaves are initiated from just two epidermal cells, and the mediolateral leaf axis is the first to be established. This pattern of development differs from that seen in flowering plants. These differences are discussed in the context of the development and evolution of diverse land plant forms.