tbuckley/cabot-search huggingface dataset:
Antitumor Activity of an Oncolytic Adenoviral-CD40 Ligand (CD154) Transgene Construct in Human Breast Cancer Cells
Authors: Erica M. Gomes, Margret S. Rodrigues, Anagha P. Phadke, Lindsay D. Butcher, Cherry Starling, Salina Chen, Dongkun Chang, Ruben Hernandez-Alcoceba, Joseph T. Newman, Marvin J. Stone, Alex W. Tong
Journal: Clinical Cancer Research (2009)

Abstract Purpose: CD40 ligand (CD40L, CD154) plays a central role in immunoregulation and also directly modulates epithelial cell growth and differentiation. We previously showed that the CD40 receptor is commonly expressed in primary breast cancer tissues. In this proof-of-principle study, we examined the breast cancer growth–regulatory activities of an oncolytic adenoviral construct carrying the CD40L transgene (AdEHCD40L). Experimental Design: In vitro and in vivo evaluations were carried out on AdEHCD40L to validate selective viral replication and CD40L transgene activity in hypoxia inducing factor-1α and estrogen receptor–expressing human breast cancer cells. Results: AdEHCD40L inhibited the in vitro growth of CD40+ human breast cancer lines (T-47D, MDA-MB-231, and BT-20) by up to 80% at a low multiplicity of infection of 1. Incorporation of the CD40L transgene reduced the effective dose needed to achieve 50% growth inhibition (ED50) by ∼10-fold. In contrast, viral and transgene expression of AdEHCD40L, as well its cytotoxicity, was markedly attenuated in nonmalignant cells. Intratumoral injections with AdEHCD40L reduced preexisting MDA-MB-231 xenograft growth in severe combined immunodeficient mice by &amp;gt;99% and was significantly more effective (P &amp;lt; 0.003) than parental virus AdEH (69%) or the recombinant CD40L protein (49%). This enhanced antitumor activity correlated with cell cycle blockade and increased apoptosis in AdEHCD40L-infected tumor cells. Conclusions: These novel findings, together with the previously known immune-activating features of CD40L, support the potential applicability of AdEHCD40L for experimental treatment of human breast cancer.
Late-breaking abstract: Cluster analysis of objectively measured physical activity in 1001 COPD patients
Authors: Rafael Mesquita, Gabriele Spina, Fabio Pitta, David Donaire-Gonzalez, Brenda M. Deering, Mehul S. Patel, Katy E. Mitchell, Jennifer Alison, Arnoldus J. R. van Gestel, Stefanie Zogg, Philippe Gagnon, Beatriz Abascal-Bolado, Barbara Vagaggini, Judith Garcia-Aymerich, Sue C. Jenkins, Elisabeth A. P. M. Romme, Samantha S.C. Kon, Paul S. Albert, Benjamin Waschki, Dinesh Shrikrishna, Sally J. Singh, Nicholas S. Hopkinson, David Miedinger, Roberto P. Benzo, François Maltais, Pierluigi Paggiaro, Zoe J. McKeough, Michael I. Polkey, Kylie Hill, William D-C. Man, Christian F. Clarenbach, Nidia A. Hernandes, Daniela Savi, Sally Wootton, Karina C. Furlanetto, Li W. Cindy Ng, Anouk W. Vaes, Christine Jenkins, Peter R. Eastwood, Diana Jarreta, Anne Kirsten, Dina Brooks, David R. Hillman, Thaís Sant'Anna, Kenneth Meijer, Selina Dürr, Malcolm Kohler, Vanessa S. Probst, Ruth Tal-Singer, Esther Garcia Gil, Jörg D. Leuppi, Peter M.A. Calverley, Frank W. J. M. Smeenk, Richard W. Costello, Marco Gramm, Roger Goldstein, Miriam Groenen, Helgo Magnussen, Emiel F.M. Wouters, Richard L. ZuWallack, Oliver Amft, Henrik Watz, Martijn A. Spruit
Journal: European Respiratory Journal (2014)

Background: Detailed analyses of physical activity (PA) measures in chronic obstructive pulmonary disease (COPD) have been insufficiently explored. We aimed to identify clusters of COPD patients based on objectively measured PA data, and to compare clinical characteristics, PA measures and PA hourly patterns between these clusters.

Methods: 1001 COPD patients (65% men; median age and FEV1: 67 yrs and 49%pred, respectively) from 10 countries were studied. PA measures and hourly patterns were analysed based on data from the multi-sensor Sensewear armband used for >=4 days. Principal component analysis was applied to PA data for dimensionality reduction, subsequently k-means cluster analysis was used to identify subgroups of COPD patients.

Results: 5 clusters were identified (Table 1).

![Figure][1] 



Cluster 1 (very inactive) spent less time in moderate-to-vigorous intensity and more time in very light intensity, whilst cluster 5 (very active) presented an opposite behaviour. Cluster 1 also presented higher body mass index, lower FEV1 and worse dyspnoea compared to other clusters. PA hourly patterns revealed that in all clusters the peak of intensity occurred before midday, but also that more inactive clusters had a more similar pattern between week and weekend (Figure 1).

Conclusions: Five subgroups of COPD patients were identified with distinct PA measures and hourly patterns. These findings may serve as a basis for tailored interventions in COPD.

 [1]: pending:yes
Arylamine <i>N</i>-Acetyltransferase Is Required for Synthesis of Mycolic Acids and Complex Lipids in <i>Mycobacterium bovis</i> BCG and Represents a Novel Drug Target
Authors: Sanjib Bhakta, Gurdyal S. Besra, Anna M. Upton, Tanya Parish, Carolyn Sholto-Douglas-Vernon, Kevin J.C. Gibson, Stuart Knutton, Siamon Gordon, Rosangela P. daSilva, Matthew C. Anderton, Edith Sim
Journal: The Journal of Experimental Medicine (2004)

Mycolic acids represent a major component of the unique cell wall of mycobacteria. Mycolic acid biosynthesis is inhibited by isoniazid, a key frontline antitubercular drug that is inactivated by mycobacterial and human arylamine N-acetyltransferase (NAT). We show that an in-frame deletion of Mycobacterium bovis BCG nat results in delayed entry into log phase, altered morphology, altered cell wall lipid composition, and increased intracellular killing by macrophages. In particular, deletion of nat perturbs biosynthesis of mycolic acids and their derivatives and increases susceptibility of M. bovis BCG to antibiotics that permeate the cell wall. Phenotypic traits are fully complemented by introduction of Mycobacterium tuberculosis nat. We infer from our findings that NAT is critical to normal mycolic acid synthesis and hence other derivative cell wall components and represents a novel target for antituberculosis therapy. In addition, this is the first report of an endogenous role for NAT in mycobacteria.
Diphenylhydantoin sodium hepatitis
Authors: U. Harinasula
Journal: JAMA (1968)

Drug-induced hepatitis developed five weeks after diphenylhydantoin sodium (Dilantin) administration. The clinical, hematologic, biochemical, and histologic features were consistent with mixed hepatocellular type of hepatic injury due to drug hypersensitivity. Clinical abnormalities and hematologic changes were reproduced by readministration of the drug, but no hepatic abnormalities recurred.
Positive Selection of Anti–Thy-1 Autoreactive B-1 Cells and Natural Serum Autoantibody Production Independent from Bone Marrow B Cell Development
Authors: Kyoko Hayakawa, Masanao Asano, Susan A. Shinton, Ming Gui, Li-Jun Wen, Joni Dashoff, Richard R. Hardy
Journal: The Journal of Experimental Medicine (2003)

A natural serum autoantibody specific for the Thy-1 glycoprotein (anti–Thy-1 autoantibody [ATA]) is produced by B-1 cells that are positively selected by self-antigen. Here, using ATAμκ transgenic mice we show that cells with this B cell receptor are negatively selected during bone marrow (BM) development. In a Thy-1 null environment, BM ATA B cells progress to a normal follicular stage in spleen. However, in a self-antigen–positive environment, development is arrested at an immature stage in the spleen, concomitant with induction of CD5. Such cells are tolerant and short-lived, different from B-1. Nonetheless, ATA-positive selection was evident by self-antigen–dependent high serum ATA production, comprising ∼90% of serum immunoglobulin M in ATAμκ mice. Splenectomy did not eliminate ATA production and transfer of tolerant splenic B cells did not induce it. These findings demonstrate that B-1 positive selection, resulting in the production of natural serum ATA, arises independently from the major pathway of BM B cell development and selection.
Sex differences in lifetime risk and first manifestation of cardiovascular disease: prospective population based cohort study
Authors: M. J. G. Leening, B. S. Ferket, E. W. Steyerberg, M. Kavousi, J. W. Deckers, D. Nieboer, J. Heeringa, M. L. P. Portegies, A. Hofman, M. A. Ikram, M. G. M. Hunink, O. H. Franco, B. H. Stricker, J. C. M. Witteman, J. W. Roos-Hesselink
Journal: BMJ (2014)

<b>Objective</b> To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework. <b>Design</b> Prospective population based cohort study. <b>Setting</b> People living in the community in Rotterdam, the Netherlands. <b>Participants</b> 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline. <b>Main outcome measures</b> First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death. <b>Results</b> During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were −7 for any cardiovascular disease, −102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and −1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke. <b>Conclusions</b> At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages.
Gene Conversion and the Evolution of Three Leucine-Rich Repeat Gene Families in Arabidopsis thaliana
Authors: Mariana Mondragon-Palomino, Brandon S. Gaut
Journal: Molecular Biology and Evolution (2005)

The high number of duplicated genes in plant genomes provides a potential template for gene conversion and unequal crossing-over. Within a gene family these two processes can render all members homogeneous or generate diversity by reassorting variants among paralogs. The latter is especially feasible in families where gene diversity confers a selective advantage and thus conversion events are likely to be retained. Consequently, the most complete record of gene conversion is expected to be most evident in gene families commonly subjected to positive selection. Here, we describe the extent and characteristics of gene conversion and unequal crossing-over in the coding and noncoding regions of nucleotide-binding site leucine-rich repeat (NBS-LRR), receptor-like kinases (RLK), and receptor-like proteins (RLP) in the plant Arabidopsis thaliana. Members of these three gene families are associated with disease resistance and their pathogen-recognition domain is a documented target of positive selection. Our bioinformatic approach to study the major family features that may influence gene conversion revealed that in these families there is a significant association between the occurrence of gene conversion and high levels of sequence similarity, close physical clustering, gene orientation, and recombination rate. We discuss these results in the context of the overlap between gene conversion and positive selection during the evolutionary expansion of the NBS-LRR, RLK, and RLP gene families.
Lichen planus and hepatitis C virus (HCV)-related chronic hepatitis: evaluation of HCV genotypes
Authors: J-M. Pawlotsky, H. Benchiki, C. Pellet, J. Duval, D. Dhumeaux, J. Revez, M. Bagot
Journal: British Journal of Dermatology (1995)

Journal Article Lichen planus and hepatitis C virus (HCV)‐related chronic hepatitis: evaluation of HCV genotypes Get access J‐M. Pawlotsky, J‐M. Pawlotsky Departments of Bacteriology and Virology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar H. Benchiki, H. Benchiki Departments of Dermatology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar C. Pellet, C. Pellet Departments of Bacteriology and Virology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar J. Duval, J. Duval Departments of Bacteriology and Virology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar D. Dhumeaux, D. Dhumeaux Departments of Hepatology and Gastroenterology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar J. Revez, J. Revez Departments of Dermatology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar M. Bagot M. Bagot Departments of Dermatology, Hopital Henri Mondor, Universite Paris XII, G‐94010 Cretil, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 133, Issue 4, 1 October 1995, Pages 666–667, https://doi.org/10.1111/j.1365-2133.1995.tb02734.x Published: 01 October 1995
Estimated prevalence of chronic Q fever among Coxiella burnetii seropositive patients with an abdominal aortic/iliac aneurysm or aorto-iliac reconstruction after a large Dutch Q fever outbreak
Authors: Julia C.J.P. Hagenaars, Peter C. Wever, André S. van Petersen, Peter J. Lestrade, Monique G.L. de Jager-Leclercq, Mirjam H.A. Hermans, Frans L. Moll, Olivier H.J. Koning, Nicole H.M. Renders
Journal: Journal of Infection (2014)
Identifying the Estrogen Receptor Coactivator PELP1 in Autophagosomes
Authors: Kazufumi Ohshiro, Suresh K. Rayala, Seiji Kondo, Amitabh Gaur, Ratna K. Vadlamudi, Adel K. El-Naggar, Rakesh Kumar
Journal: Cancer Research (2007)

Abstract Resveratrol, a well-established phytoestrogen and chemopreventive agent, has gained much attention among oncologists because it can act as both estrogen receptor agonist and antagonist, depending on dosage and cell context. It is increasingly accepted that steroidal receptor coregulators may also function in the cytoplasmic compartment. Deregulation and altered localization of these coregulators could influence target gene expression and participate in the development of hormone-responsive cancers. Proline-, glutamic acid–, and leucine-rich protein-1 (PELP1), a novel estrogen receptor (ER) coactivator, plays an important role in the genomic and nongenomic actions of ER. Furthermore, recent studies have shown that differential compartmentalization of PELP1 could be crucial in modulating sensitivity to tamoxifen. In this study, we investigated the role of PELP1 in resveratrol-induced autophagy in lung cancer and salivary gland adenocarcinoma cell lines. Resveratrol reversibly inhibited the growth of these cancer cell lines and induced autophagy, as evidenced by microtubule-associated protein 1 light chain 3 (LC3) up-regulation in a time-dependent and 3-methyladenine–sensitive manner. Confocal microscopic analysis showed that resveratrol induced PELP1 accumulation in autophagosomes with green fluorescent protein-LC3. The intermediary molecule involved in PELP1 accumulation in resveratrol-induced autophagosomes is hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a trafficking molecule that binds to PELP1. These results identify PELP1 for the first time in autophagosomes, implying that both PELP1 and HRS reallocate to autophagosomes in response to resveratrol treatment, which might be important in the process of autophagy in the cancer cells. [Cancer Res 2007;67(17):8164–71]
STUDIES ON THE IN VIVO AND IN VITRO MULTIPLICATION OF THE LDH VIRUS OF MICE
Authors: Herman G. du Buy, Martin L. Johnson
Journal: The Journal of Experimental Medicine (1966)

In vivo analysis of the virus titer in various loci, 24 hr after infection, showed that a titer similar to that in the blood plasma was found in the ascitic fluid of Erlich ascites cancer-bearing mice, and in lymph nodes, spleen, and thymus, i.e. loci which contain macrophages as a common cell type. However, only in the lymph nodes and in the ascitic fluid did the increase in virus titer precede or parallel the increase in the plasma. The LDH virus titer in the plasma of X-irradiated mice was similar to that of control mice, eliminating radiation-sensitive cells but not macrophages as target cells of the virus. Electron microscopic observation of infected lymph node cells revealed the presence of two types of particles: one consisting of small densely stained annuli, about 25 mmicro in diameter and one of similar dense annuli with a halo extending the diameter to about 50 mmicro. Such particles were repeatedly observed within single or double membraned vesicles. In vitro, the LDH virus multiplied only in cultures of mouse peritoneal macrophages, maintained in medium 199 with 10% FBS. The virus titer could be maintained for at least 33 days, during eleven serial passages, involving an overall dilution factor of 10(11). These results corroborate the findings of Evans and Salaman, who used peritoneal macrophages maintained in Eagle's medium and 5 to 10% lamb serum. However, in the serial passage experiments reported here, the virus titer could only be maintained following trypsinization of each successive inoculum. The role of macrophages as the target cell for LDH virus multiplication in vivo is discussed.
Attenuated poxviruses generate clinically relevant frequencies of CMV-specific T cells
Authors: Zhongde Wang, Corinna La Rosa, Shahram Mekhoubad, Simon F. Lacey, Maria C. Villacres, Susan Markel, Jeff Longmate, Joshua D. I. Ellenhorn, Robert F. Siliciano, Christopher Buck, William J. Britt, Don J. Diamond
Journal: Blood (2004)
Novel Baroreflex Activation Therapy in Resistant Hypertension
Authors: Ingrid J.M. Scheffers, Abraham A. Kroon, Jürg Schmidli, Jens Jordan, Jan J.M. Tordoir, Markus G. Mohaupt, Friedrich C. Luft, Hermann Haller, Jan Menne, Stefan Engeli, Jiri Ceral, Siegfried Eckert, Andrejs Erglis, Krzysztof Narkiewicz, Thomas Philipp, Peter W. de Leeuw
Journal: Journal of the American College of Cardiology (2010)
The effect of birth-weight on longitudinal lung spirometry in school age children and adolescents born at term
Authors: Sarah Kotecha, W. John Watkins, John Henderson, Sailesh Kotecha
Journal: European Respiratory Journal (2014)

Introduction   Whilst it is increasingly accepted long term lung function outcomes may have their origins in early life, it is unclear what effect birth-weight has on later lung function in term-born children.   Aims and objectives   We determined how birth-weight effected lung function measurements in childhood and adolescence in term-born children.   Methods   Data for Caucasian, term-born, singleton, live births from the Avon Longitudinal Study of Parents and Children was used to determine the association between birth-weight and gestation and lung function at 8-9 (n=5320) and 14-17 (n=3474) years of age.   Results   At age 8-9, standardised birth-weight (adjusted for age, height and gender) was significantly associated with lung function. This relationship was essentially unchanged when birth-weight was further adjusted for gestational age and for confounders. At age 14-17, the association between standardised birth-weight and spirometry measures remained significant for FVC and FEV 1  but were not for FEF 25-75 . The estimated differences for FEV 1  were 31 and 43ml for a 1 Kg difference in birth-weight at 8-9 and 14-17 years of age respectively.   Conclusions   Birth-weight had an effect on later respiratory outcomes in term-born children suggesting that interventions to achieve optimal birth-weight at term may prevent later deficits in lung function.
Pulmonary dendritic cells: playing ball in the BAL?
Authors: I. K. Demedts, G. F. Joos, G. G. Brusselle
Journal: European Respiratory Journal (2007)

The lung is one of the few organs in the human body where there is a continuous and extensive interaction between the environment and our immune system. With every breath we take, numerous airborne particles, both harmless as well as potentially dangerous, are inhaled into the airways. The big challenge for the pulmonary immune system is to discriminate the good from the bad and to react accordingly. Unnecessary action against harmless particles ( e.g. innocent antigens, self proteins) should be avoided, while a rapid and strong immune response is needed against potentially dangerous microorganisms. Pulmonary dendritic cells (DCs) are ideally suited to maintain this delicate balance between tolerance and active immune responses 1. DCs are antigen-presenting cells that play a central role in host immune defence, by linking innate with adaptive immune responses 2. They recognise danger signals from invading pathogens and are able to prime naive T-cells and to initiate appropriate T-cell immune responses against these microorganisms 3. Indeed, T-lymphocytes themselves are actually “blind” to unprocessed antigens, and require the assistance of antigen presenting cells, such as DCs and macrophages, to be able to recognise antigens. Moreover, by the release of inflammatory cytokines, DCs influence the polarisation of the adaptive T-cell response into either a T-helper cell type (Th)1-, Th2- or a T-regulatory cell-direction 4. This enables them not only to initiate active immune responses, but also to control and dampen these immune responses, as well as to avoid unwanted immune responses against …