tbuckley/cabot-search huggingface dataset:
Differential Response of Human and Mouse Dendritic Cells to VEGF Determines Interspecies Discrepancies in Tumor-Mediated Th1/Th2 Polarity Shift
Authors: Matthew S. Block, Wendy K. Nevala, Alexey A. Leontovich, Svetomir N. Markovic
Journal: Clinical Cancer Research (2011)

Abstract Purpose: Metastatic cancer patients exhibit systemic dysregulation of immune polarity and are biased toward Th-2 immune responses. This is due, at least in part, to effects of VEGF on antigen presenting cell (APC) function. We therefore compared immune polarity changes in mouse models of cancer with those seen in human patients. Experimental Design: We measured plasma levels of vascular growth factors and multiple cytokines via ELISA and multiplex analysis in mice with transplantable and spontaneous tumors. We compared immune cell subsets in naive and vaccinated mice with and without tumors. We assessed cytokine immune responses by multiplex analysis. Finally, we assessed gene expression and receptor surface expression in response to VEGF in mouse and human APCs. Results: Although human patients have elevated plasma cytokines and altered immune polarity in response to antigen, mice have minimal immune abnormalities. Mouse VEGF does not mediate immune repolarization in vitro. Human but not mouse APCs upregulate VEGFR2 and downregulate interleukin (IL)-12β in response to VEGF. Conclusions: Whereas humans with metastatic cancer demonstrate dysregulated immune polarity in response to excess plasma VEGF, tumor mice do not. This appears to be due to differences in APC responses to VEGF stimulation. Differential immune effects of VEGF may represent a key species difference in the context of translation of preclinical cancer immunotherapeutics into early clinical testing. Clin Cancer Res; 17(7); 1776–83. ©2011 AACR.
Reversal of gene dysregulation in cultured cytotrophoblasts reveals possible causes of preeclampsia
Authors: Yan Zhou, Matthew J. Gormley, Nathan M. Hunkapiller, Mirhan Kapidzic, Yana Stolyarov, Victoria Feng, Masakazu Nishida, Penelope M. Drake, Katherine Bianco, Fei Wang, Michael T. McMaster, Susan J. Fisher
Journal: Journal of Clinical Investigation (2013)

During human pregnancy, a subset of placental cytotrophoblasts (CTBs) differentiates into cells that aggressively invade the uterus and its vasculature, anchoring the progeny and rerouting maternal blood to the placenta. In preeclampsia (PE), CTB invasion is limited, reducing placental perfusion and/or creating intermittent flow. This syndrome, affecting 4%-8% of pregnancies, entails maternal vascular alterations (e.g., high blood pressure, proteinuria, and edema) and, in some patients, fetal growth restriction. The only cure is removal of the faulty placenta, i.e., delivery. Previously, we showed that defective CTB differentiation contributes to the placental component of PE, but the causes were unknown. Here, we cultured CTBs isolated from PE and control placentas for 48 hours, enabling differentiation and invasion. In various severe forms of PE, transcriptomics revealed common aberrations in CTB gene expression immediately after isolation, including upregulation of SEMA3B, which resolved in culture. The addition of SEMA3B to normal CTBs inhibited invasion and recreated aspects of the PE phenotype. Additionally, SEMA3B downregulated VEGF signaling through the PI3K/AKT and GSK3 pathways, effects that were observed in PE CTBs. We propose that, in severe PE, the in vivo environment dysregulates CTB gene expression; the autocrine actions of the upregulated molecules (including SEMA3B) impair CTB differentiation, invasion and signaling; and patient-specific factors determine the signs.
MRI of the wrist in early rheumatoid arthritis
Authors: C G Peterfy
Journal: Annals of the Rheumatic Diseases (2004)

Can it be used to predict long term functional outcome?

The past several years have witnessed unprecedented advances in rheumatology, with the introduction of several new compounds capable of halting the relentless progression of joint destruction and functional disability in patients with rheumatoid arthritis (RA). With these successes, however, have come new pressures for medical imaging to resolve even the slightest traces of erosive joint damage and to identify pre-erosive inflammatory features that can accurately predict which patients will go on to severe functional debility if they do not receive aggressive structure modifying treatment immediately.

Before the introduction of effective treatment, rheumatology’s demand for imaging joint structure was modest, at best (fig 1). Although it was widely accepted that joint damage was a key driver of functional disability in RA, particularly in late disease,1–3 without effective treatments to prevent erosive destruction, there was limited need for detailed information about the integrity of joint structure. Magnetic resonance imaging (MRI) promised to tell more about bone erosion, synovitis, and the integrity of cartilage, ligaments and other articular tissues than radiography ever could, but the additional cost and inconveniences associated with MRI were not felt to be worth the extra performance. The information simply did not impact on clinical management. Accordingly, most rheumatologists focused primarily on clinical and laboratory features of the disease, and used imaging only sparingly—if at all. Not surprisingly, the development of MRI for this purpose languished. However, the recent introduction of effective structure modifying treatments has changed the way that rheumatologists manage patients with RA, and this has created new demands on imaging both in clinical practice and in clinical research.



 Figure 1  
Technical demand-performance relationships for radiography and MRI in RA. (A) Before the availability of effective structure modifying treatment, clinical rheumatology’s demand for technical performance in imaging …
Effect of non-invasive ventilation on respiratory muscle loading and endurance in patients with Duchenne muscular dystrophy
Authors: M Toussaint, P Soudon, W Kinnear
Journal: Thorax (2007)

<h3>Background:</h3> Respiratory muscle weakness in patients with Duchenne muscular dystrophy (DMD) leads to respiratory failure for which non-invasive positive pressure ventilation (NIPPV) is an effective treatment. This is used initially at night (n-NIPPV) but, as the disease progresses, diurnal use (d-NIPPV) is often necessary. The connection between NIPPV and relief of respiratory muscle fatigue remains unclear. A study was undertaken to determine the extent to which n-NIPPV and d-NIPPV unload the respiratory muscles and improve respiratory endurance in patients with DMD. <h3>Methods:</h3> Fifty patients with DMD were assessed at 20.00 and 08.00 h. More severely affected patients with nocturnal hypoventilation received n-NIPPV; those with daytime dyspnoea also received d-NIPPV via a mouthpiece (14.00–16.00 h). Lung function, modified Borg dyspnoea score, spontaneous breathing pattern, tension-time index (TT<sub>0.1</sub> = occlusion pressure (P<sub>0.1</sub>)/maximum inspiratory pressure (MIP) × duty cycle (Ti/Ttot)) and respiratory muscle endurance time (Tlim) against a threshold load of 35% MIP were measured. <h3>Results:</h3> More severe respiratory muscle weakness was associated with a higher TT<sub>0.1</sub> and lower Tlim. In contrast to non-dyspnoeic patients, patients with dyspnoea (Borg score &gt;2.5/10) showed an increase in Tlim and decrease in TT<sub>0.1</sub> after n-NIPPV. At 16.00 h, immediately after d-NIPPV, patients with dyspnoea had lower TT<sub>0.1</sub> and Borg scores with unchanged Tlim. Compared with the control day without d-NIPPV, TT<sub>0.1</sub>, Borg scores and Tlim were all improved at 20.00 h. <h3>Conclusions:</h3> In patients with dyspnoea with DMD, the load on respiratory muscles increases and endurance capacity decreases with increasing breathlessness during the day, and this is reversed by n-NIPPV. An additional 2 h of d-NIPPV unloads respiratory muscles and reverses breathlessness more effectively than n-NIPPV alone.
Efficacy of Breast Cancer Screening in the Community According to Risk Level
Authors: Joann G. Elmore, Lisa M. Reisch, Mary B. Barton, William E. Barlow, Sharon Rolnick, Emily L. Harris, Lisa J. Herrinton, Ann M. Geiger, R. Kevin Beverly, Gene Hart, Onchee Yu, Sarah M. Greene, Noel S. Weiss, Suzanne W. Fletcher
Journal: JNCI Journal of the National Cancer Institute (2005)

The efficacy of breast cancer screening in the community may differ from that suggested by the results of randomized trials, and no data have been available on efficacy among women who have different levels of breast cancer risk.We conducted a matched case-control study among women enrolled in six health plans in Washington, Oregon, California, Massachusetts, and Minnesota. We examined the efficacy of screening by mammography and/or clinical breast examination among women in two age cohorts (40-49 years and 50-65 years) and in two breast cancer risk levels (average and increased risk). Women who died from breast cancer from January 1, 1983, through December 31, 1998, (N = 1351; case subjects) were matched to control subjects (N = 2501) on age and risk level. Increased risk was defined as a family history of breast cancer or a breast biopsy noted in the medical records before the index date (defined as date of first suspicion of breast abnormalities in case subjects, with the same date used for matched control subjects). Data on screening, risk status, and other variables were abstracted from medical records. Conditional logistic regression was used to examine the association between breast cancer mortality and receipt of screening. All statistical tests were two-sided.There were small, non-statistically significant associations between breast cancer mortality and receipt of screening during the 3 years prior to the index date for both the younger women [odds ratio (OR) = 0.92; 95% confidence interval (CI) = 0.76 to 1.13] and the older women (OR = 0.87; 95% CI = 0.68 to 1.12). The association among women at increased risk (OR = 0.74; 95% CI = 0.50 to 1.03) was stronger than that among women at average risk (OR = 0.96; 95% CI = 0.80 to 1.14), but the difference was not statistically significant (P = .17).In this community-based study, screening history was not associated with breast cancer mortality. However, potential limitations of this study argue for a cautious interpretation of these findings.
Progressive Recombination Suppression and Differentiation in Recently Evolved Neo-sex Chromosomes
Authors: Heini M. Natri, Takahito Shikano, Juha Merilä
Journal: Molecular Biology and Evolution (2013)

Recombination suppression leads to the structural and functional differentiation of sex chromosomes and is thus a crucial step in the process of sex chromosome evolution. Despite extensive theoretical work, the exact processes and mechanisms of recombination suppression and differentiation are not well understood. In threespine sticklebacks (Gasterosteus aculeatus), a different sex chromosome system has recently evolved by a fusion between the Y chromosome and an autosome in the Japan Sea lineage, which diverged from the ancestor of other lineages approximately 2 Ma. We investigated the evolutionary dynamics and differentiation processes of sex chromosomes based on comparative analyses of these divergent lineages using 63 microsatellite loci. Both chromosome-wide differentiation patterns and phylogenetic inferences with X and Y alleles indicated that the ancestral sex chromosomes were extensively differentiated before the divergence of these lineages. In contrast, genetic differentiation appeared to have proceeded only in a small region of the neo-sex chromosomes. The recombination maps constructed for the Japan Sea lineage indicated that recombination has been suppressed or reduced over a large region spanning the ancestral and neo-sex chromosomes. Chromosomal regions exhibiting genetic differentiation and suppressed or reduced recombination were detected continuously and sequentially in the neo-sex chromosomes, suggesting that differentiation has gradually spread from the fusion point following the extension of recombination suppression. Our study illustrates an ongoing process of sex chromosome differentiation, providing empirical support for the theoretical model postulating that recombination suppression and differentiation proceed in a gradual manner in the very early stage of sex chromosome evolution.
Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma
Authors: Alessandro Rambaldi, Emanuela Carlotti, Elena Oldani, Irene Della Starza, Michele Baccarani, Sergio Cortelazzo, Francesco Lauria, Luca Arcaini, Enrica Morra, Alessandro Pulsoni, Luigi Rigacci, Maurizio Rupolo, Francesco Zaja, Pier Luigi Zinzani, Tiziano Barbui, Robert Foa
Journal: Blood (2005)
Impact Of Formula Containing Docosahexaenoic Acid, Prebiotics, and Beta-Glucan On Allergic Manifestations In Young Children
Authors: Deolinda Scalabrin, Suzanne Stolz, Weihong Zhuang, Mariana Pontes, Angela de Mattos, Indhira Almeida, Carolina Godoy, Sara Gatto, Vivian Leal, Gabriela Cabral, Tereza Ribeiro, Hugo Ribeiro
Journal: Journal of Allergy and Clinical Immunology (2014)
The year in Gut 2009
Authors: R. Spiller
Journal: Gut (2009)

This will be the last Editorial I shall write as Editor, having completed my 7 year term at the end of this year, so it is perhaps appropriate to look back at what has been achieved and also to look forward. It gives me great pleasure to thank my many Associate Editors from all over the world who have contributed to Gut ’s success. I am particularly grateful to the early members of my team including my deputy John Atherton (Nottingham, UK), Alistair Watson (Liverpool, UK), Juergen Scholmerich (Regensburg, Germany), Ray Playford (London, UK), David Adams (Birmingham, UK), Jan Tack (Leuven, Belgium) and Anna Mae Diehl (Baltimore, USA) who encouraged me to raise the standards by which we judged papers. This led to the rise in impact factor (figure) which has in turn attracted the many excellent manuscripts we are now receiving.



The Associate Editors have had a big impact on the journal, attracting papers from new areas and new authors, and have also expanded our pool of international reviewers, something which is vital for the journal's efficient working. We were soon joined by Markus Lerch (Greifswald, Germany) and Jean-Frederic Colombel (Lille, France), attracting more papers from the pancreatic and inflammatory bowel disease community, respectively. Their successors have been an outstandingly talented group with whom it has been a privilege to work. Kevin Moore (London, UK), Geoff Dusheiko (London, UK), Emad El-Omar (Aberdeen, UK), Subrata Ghosh (London, UK), Massimo Pinzani (Florence, Italy), Magnus Simren (Gothenberg, Sweden), Bill Grady (Seattle, USA), Alexander Gerbes (Munich, Germany), David Mutimer (Birmingham, UK), …
Phase I safety study of escalating doses of atrasentan in adults with recurrent malignant glioma
Authors: Surasak Phuphanich, Kathryn A. Carson, Stuart A. Grossman, Glenn Lesser, Jeffrey Olson, Tom Mikkelsen, Serena Desideri, Joy D. Fisher
Journal: Neuro-Oncology (2008)

Atrasentan is an oral selective endothelin-A receptor antagonist that may inhibit cell proliferation and interfere with angiogenesis during glioma growth. We conducted a dose-finding study to assess atrasentan's safety and toxicity and to gather preliminary evidence of efficacy. Patients with recurrent malignant glioma received oral atrasentan at >or=10 mg/day. We increased the dose among cohorts until the maximum tolerated dose (MTD) was defined. Patients were evaluated for response every 8 weeks and remained on the study until the tumor progressed or toxicities occurred. Twenty-five patients were enrolled, with a median age of 53 years (range, 25-70) and a median KPS of 90% (range, 60-100%). Twenty-two patients had glioblastoma multiforme (GBM), 2 had anaplastic astrocytoma, and 1 had an anaplastic oliogodendroglioma; 24 patients had received one prior chemo therapy regimen before being enrolled in the study. The most common atrasentan-related toxicities were grade 1 or 2 rhinitis, fatigue, and edema. One patient developed grade 3 hypoxia and peripheral edema at a dose of 90 mg/day. We observed no dose-limiting toxicities in an expanded cohort of 10 patients at 70 mg/day, which was declared the MTD. Two partial responses (8%) were seen in patients with GBM at the 70- and 90-mg/day dose levels, and 4 patients had stable disease before progressing. Nineteen patients have died, and median survival was 6.0 months (95% confidence interval, 4.2-9.5 months). We conclude that the MTD of daily oral atrasentan in patients with recurrent malignant glioma is 70 mg/day. Further study of atrasentan with radiation therapy and temozolomide in newly diagnosed GBM is warranted to evaluate the efficacy of this novel agent.
Restoring Methicillin-Resistant <i>Staphylococcus aureus</i> Susceptibility to β-Lactam Antibiotics
Authors: Christopher M. Tan, Alex G. Therien, Jun Lu, Sang H. Lee, Alexandre Caron, Charles J. Gill, Christian Lebeau-Jacob, Liliana Benton-Perdomo, João M. Monteiro, Pedro M. Pereira, Nathaniel L. Elsen, Jin Wu, Kathleen Deschamps, Mihai Petcu, Simon Wong, Etienne Daigneault, Susanne Kramer, Lianzhu Liang, Eugene Maxwell, David Claveau, John Vaillancourt, Kathryn Skorey, John Tam, Hao Wang, Timothy C. Meredith, Susan Sillaots, Lisa Wang-Jarantow, Yeeman Ramtohul, Eric Langlois, France Landry, John C. Reid, Gopal Parthasarathy, Sujata Sharma, Anastasia Baryshnikova, Kevin J. Lumb, Mariana G. Pinho, Stephen M. Soisson, Terry Roemer
Journal: Science Translational Medicine (2012)

Methicillin-resistant Staphylococcus aureus infection can be treated effectively by combining a β-lactam antibiotic with a drug that targets FtsZ.
A British Medical Association Lecture on PREDESTINATION IN DISEASE
Authors: W. L. Brown
Journal: BMJ (1930)

TilE AVoId " l" prcd(stiuiatioi '' brings tllhe Pgimil figulre of Calvini beforc the miiind.Btut it is niot wi-itlh the tlheolog,ical aspects that I wish to deal.Tlle flames of hell have lost tlhCir terrlor', buit as iuani1 must be frightenied about somie- thiing, he terrifies liliiiself about germs or cancer or whether lie is eatinlg enouglh vitamins.This fills the void, wllich disbelief in hell lhas left, quite satisfactorily.True, tho sciemitific doctrine of detcinmiiimisin approxminiates to pre- destiniation.Oni that -iew every act is predetcrmiiied bv otur reaction to sonic afferenit impulse determiined bv our original miake-up as miiodified by tIe cffcct of prev-ious imipulses.This doctrinie lhas beeni carried to its logical conielusion bvy li'end w-hel lie miiaimitmmins thiat slips of the tonigue or pen aniid forgetfuliless aire thIe result of causes wh-ichl can he discovered and wlichl tlhrow light oni the work- inig of the unconscious lev-el of ouir minds.Oni this view the onilv valriable factor in a im.aii's belhaviour comlles from Isis environment, whlich lmay vary the kinid of stimiiulus lie receives-the rest is predestined.
The Role of miR-18b in MDM2-p53 Pathway Signaling and Melanoma Progression
Authors: Altaf A Dar, Shahana Majid, Claudia Rittsteuer, David de Semir, Vladimir Bezrookove, Schuyler Tong, Mehdi Nosrati, Richard Sagebiel, James R. Miller, Mohammed Kashani-Sabet
Journal: JNCI Journal of the National Cancer Institute (2013)

Although p53 is inactivated by point mutations in many tumors, melanomas infrequently harbor mutations in the p53 gene. Here we investigate the biological role of microRNA-18b (miR-18b) in melanoma by targeting the MDM2-p53 pathway.Expression of miR-18b was examined in nevi (n = 48) and melanoma (n = 92) samples and in melanoma cell lines and normal melanocytes. Immunoblotting was performed to determine the expression of various proteins regulated by miR-18b. The effects of miR-18b overexpression in melanoma cell lines were investigated using assays of colony formation, cell viability, migration, invasion, and cell cycle and in a xenograft model (n = 10 mice per group). Chromatin immunoprecipitation and methylation assays were performed to determine the mechanism of microRNA silencing.Expression of miR-18b was substantially reduced in melanoma specimens and cell lines by virtue of hypermethylation and was reinduced (by 1.5- to 5.3-fold) in melanoma cell lines after 5-AZA-deoxycytidine treatment. MDM2 was identified as a target of miR-18b action, and overexpression of miR-18b in melanoma cells was accompanied by 75% reduced MDM2 expression and 2.5-fold upregulation of p53, resulting in 70% suppression of melanoma cell colony formation. The effects of miR-18b overexpression on the p53 pathway and on melanoma cell growth were reversed by MDM2 overexpression. Stable overexpression of miR-18b produced potent tumor suppressor activity, as evidenced by suppressed melanoma cell viability, induction of apoptosis, and reduced tumor growth in vivo. miR-18b overexpression suppressed melanoma cell migration and invasiveness and reversed epithelial-to-mesenchymal transition.Our results demonstrate a novel role for miR-18b as a tumor suppressor in melanoma, identify the MDM2-p53 pathway as a target of miR-18b action, and suggest miR-18b overexpression as a novel strategy to reactivate the p53 pathway in human tumors.
Memory T cells are anergic to the superantigen staphylococcal enterotoxin B.
Authors: W T Lee, E S Vitetta
Journal: The Journal of Experimental Medicine (1992)

We have used staphylococcal enterotoxin B (SEB) to study the role of naive and memory T cells in the induction of peripheral tolerance. After administration of SEB to mice, the numbers of naive and memory T cells increase, as does the proportion of memory T cells, which are unresponsive to further stimulation with SEB in vitro. In addition, memory T cells generated in response to conventional antigen, which proliferate and provide help to B cells in the presence of the conventional antigen, fail to respond to superantigen. Hence, memory T cells, in general, are anergized by SEB. These results suggest that SEB-induced activation and anergy reflect the combined responses of naive and memory T cells. The differential activation vs. anergy of naive and memory T cells by superantigen may be related to cytokine production and may play an important role in the etiology of autoimmune diseases or immunodeficiency diseases such as acquired immune deficiency syndrome.
Cell-cell interaction in the heart via Wnt/ -catenin pathway after cardiac injury
Authors: A. Deb
Journal: Cardiovascular Research (2014)

The adult mammalian heart predominantly comprises myocytes, fibroblasts, endothelial cells, smooth muscle cells, and epicardial cells arranged in a precise three-dimensional framework. Following cardiac injury, the spatial arrangement of cells is disrupted as different populations of cells are recruited to the heart in a temporally regulated manner. The alteration of the cellular composition of the heart after cardiac injury thus enables different phenotypes of cells to interact with each other in a spatio-temporal-dependent manner. It can be argued that the integrated study of such cellular interactions rather than the examination of single populations of cells can provide more insights into the biology of cardiac repair especially at an organ-wide level. Many signalling systems undoubtedly mediate such cross talk between cells after cardiac injury. The Wnt/β-catenin system plays an important role during cardiac development and disease. Here, we describe how cell populations in the heart after cardiac injury mediate their interactions via the Wnt/β-catenin pathway, determine how such interactions can affect a cardiac repair response and finally suggest an integrated approach to study cardiac cellular interactions.