tbuckley/cabot-search huggingface dataset:
Body mass index and Barrett's oesophagus in women
Authors: B C Jacobson, A T Chan, E L Giovannucci, C S Fuchs
Journal: Gut (2009)

Excess body mass is associated with symptoms of gastro-oesophageal reflux disease, and cross-sectional studies suggest an association between body mass index (BMI) and Barrett's oesophagus. The present study sought prospectively to examine the influence of BMI and other anthropomorphic measures on the risk for Barrett's oesophagus among women.This was a prospective study of 15 861 women who participated in the Nurses' Health Study, without a history of cancer, who underwent upper gastrointestinal endoscopy for any reason between 1986 and 2004. The main outcome measures were 261 cases of pathologically confirmed specialised intestinal metaplasia within the oesophagus (Barrett's oesophagus). Self-reported data on weight were collected from biennial questionnaires. Self-reported height was collected in 1976, and self-reported waist and hip circumferences were collected in 1986.Compared with women with a BMI of 20-24.9 kg/m(2), women with a BMI of 25-29.9 had a multivariate OR for Barrett's oesophagus of 0.92 (95% CI 0.66 to 1.27), women with a BMI > or =30 had a multivariate OR of 1.52 (95% CI 1.02 to 2.28) and women with a BMI <20 had a multivariate OR of 0.92 (95% CI 0.65 to 1.31). Results were similar when controlling for symptoms of gastro-oesophageal reflux, and among the entire Nurses' Health Study cohort (n = 93 609) regardless of a history of endoscopy. In contrast, waist-to-hip ratio, waist circumference and height did not appear to be associated with Barrett's oesophagus.Obese, but not overweight, women appear to be at increased risk for Barrett's oesophagus.
Characterization of antimitochondrial antibodies in healthy adults
Authors: Alberto Mattalia, Stefano Quaranta, Patrick S.C. Leung, Marzia Bauducci, Judy Van de Water, Pier Luigi Calvo, Franca Danielle, Mario Rizzetto, Aftab Ansari, Ross L. Coppel, Floriano Rosina, M. Eric Gershwin
Journal: Hepatology (1998)

The detection of antimitochondrial antibodies (AMAs) is an important criterion for the diagnosis of primary biliary cirrhosis (PBC). During the last decade, the mitochondrial autoantigens have been cloned, sequenced, and identified as members of the 2-oxo-acid dehydrogenase pathway, including the E2 subunits of pyruvate dehydrogenase (PDC-E2), branched-chain 2-oxo-acid dehydrogenase (BCOADC-E2), and 2-oxo-glutarate dehydrogenase (OGDC-E2). We have developed a rapid and sensitive diagnostic test for use in PBC based on a triple hybrid recombinant molecule (r-MIT3) that contains the autoepitopes of PDC-E2, BCOADC-E2, and OGDC-E2. To help understand the frequency and antigen specificity of AMAs in an asymptomatic population and to identify patients with early disease, we investigated the prevalence of AMA, by enzyme-linked immunosorbent assay (ELISA), in a cohort of 1,530 people from northern Italy. Positive sera were further analyzed for immunoglobulin (Ig) isotypes, subclasses, and epitopes of AMA by a combination of ELISA and immunoblotting. In this cohort of 1,530 people, 9 (0.5%) reacted to r-MIT3 by ELISA. Of the 9 reactive sera, 2 recognized PDC-E2, 2 of 9 recognized BCOADC-E2, 1 of 9 recognized OGDC-E2, 2 of 9 recognized both PDC-E2 and BCOADC-E2, and 1 of 9 recognized PDC-E2 and OGDC-E2. AMA reactivity was primarily IgM and IgA. Epitope mapping revealed an AMA pattern of reactivity to PDC-E2 that differed from that found in patients with histologically proven PBC in most of the sera. However, 1 sera of a 72-year-old female with a normal alkaline phosphatase had an AMA profile identical to typical PBC. After a variable follow-up period (8-14 months), sera from 8 of 9 of these people were re-obtained for AMA and relative epitope mapping. Interestingly, the reactivity had a wider AMA pattern than before.
Multifunctional Nanoparticles for Drug Delivery and Molecular Imaging
Authors: Gang Bao, Samir Mitragotri, Sheng Tong
Journal: Annual Review of Biomedical Engineering (2013)

Recent advances in nanotechnology and growing needs in biomedical applications have driven the development of multifunctional nanoparticles. These nanoparticles, through nanocrystalline synthesis, advanced polymer processing, and coating and functionalization strategies, have the potential to integrate various functionalities, simultaneously providing (a) contrast for different imaging modalities, (b) targeted delivery of drug/gene, and (c) thermal therapies. Although still in its infancy, the field of multifunctional nanoparticles has shown great promise in emerging medical fields such as multimodal imaging, theranostics, and image-guided therapies. In this review, we summarize the techniques used in the synthesis of complex nanostructures, review the major forms of multifunctional nanoparticles that have emerged over the past few years, and provide a perceptual vision of this important field of nanomedicine.
Lung mechanics after cardiac valve replacement.
Authors: M J Morris, M M Smith, B G Clarke
Journal: Thorax (1980)

Fourteen patients undergoing single aortic or mitral valve replacement had measurements made of lung volumes, static pressure-volume (P-V) relationships, and conductance-pressure relationships during deflation before operation and again between one and two years later. At follow-up, total lung capacity (TLC), functional residual capacity (FRC), residual volume (RV), and static tidal compliance (slope of static P-V deflation line for one litre above FRC) had increased significantly, in association with a decrease in heart size. There was a change in the shape and position of some P-V curves both in the aortic and mitral patients. In the patients with aortic disease P-V deflation curves shifted to the left after operation. In the patients with mitral disease the P-V deflation curves before operation crossed those measured after operation, so that at high lung volumes recoil became less after operation, but at low lung volumes recoil increased. Conductance had increased at high lung volumes. The data suggest that in longstanding pulmonary congestion, airways are more rigid making them less distensible at high and less compressible at low transpulmonary pressures than after operation when congestion has been at least partly relieved.
T Helper Type 2 Cell Differentiation Occurs in the Presence of Interleukin 12 Receptor β2 Chain Expression and Signaling
Authors: Ryuta Nishikomori, Rolf O. Ehrhardt, Warren Strober
Journal: The Journal of Experimental Medicine (2000)

The differentiation of CD4(+) T cells into T helper type 1 (Th1) cells is driven by interleukin (IL)-12 through the IL-12 receptor beta2 (IL-12Rbeta2) chain, whereas differentiation into Th2 cells is driven by IL-4, which downregulates IL-12Rbeta2 chain. We reexamined such differentiation using IL-12Rbeta2 chain transgenic mice. We found that CD4(+) T cells from such mice were able to differentiate into Th2 cells when primed with IL-4 or IL-4 plus IL-12. In the latter case, the presence of IL-4 suppressed interferon (IFN)-gamma production 10-100-fold compared with cells cultured in IL-12 alone. Finally, in studies of the ability of IL-12 to convert Th2 cells bearing a competent IL-12R to the Th1 cells, we showed that: (a) T cells bearing the IL-12Rbeta2 chain transgene and primed under Th2 conditions could not be converted to Th1 cells by repeated restimulation under Th1 conditions; and (b) established Th2 clones transfected with the IL-12Rbeta2 chain construct continued to produce IL-4 when cultured with IL-12. These studies show that IL-4-driven Th2 differentiation can occur in the presence of persistent IL-12 signaling and that IL-4 inhibits IFN-gamma production under these circumstances. They also show that established Th2 cells cannot be converted to Th1 cells via IL-12 signaling.
Intranasal Toll-like Receptor 8 Agonist (VTX-1463) Significantly Improves Symptoms of Allergic Rhinitis in a Randomized, Placebo-Controlled Trial
Authors: F. Horak, P. Zieglmayer, R. Zieglmayer, P. Lemell, M. Newkirk, K. Manjarrez, T.D. Randall, R. Hershberg
Journal: Journal of Allergy and Clinical Immunology (2011)
Heparin Inhibits Eicosanoid Metabolism and Hyperventilation-induced Bronchoconstriction in Dogs
Authors: RYOICHI SUZUKI, ARTHUR N. FREED
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Inhalation of heparin, an anticoagulant, attenuates exercise- induced asthma (EIA) in human subjects. The purpose of this study was to determine if heparin inhibits hyperventilation-induced bronchoconstriction (HIB) in a canine model of EIA, and if its mode of action involves the inhibition of eicosanoid mediator production and release. We used a wedged bronchoscope technique to measure baseline peripheral airway resistance (Rp). We then performed either a 2-min or 5-min dry air challenge (DAC) by temporarily increasing from 200 to 2,000 ml/min the flow of 5% CO2 in air used to ventilate a wedged sublobar segment. We compared HIB before and 60 min after aerosol treatment with either bacteriostatic water (BW) or heparin. We found that (1) heparin had no effect on baseline Rp, (2) BW did not alter the response to DAC, and (3) heparin reduced HIB by ∼ 50–60%. On the basis of bronchoalveolar lavage fluid (BALF) cell analysis, heparin and BW caused acute infiltration of macrophages and eosinophils, and heparin increased the number of erythrocytes recovered immediately after DAC. Despite these acute inflammatory effects initiated prior to DAC, BALF mediator analyses revealed that pretreatment with heparin either attenuated or abolished hyperventilation-induced leukotriene, prostaglandin, and thromboxane release. Thus, our data provide direct evidence that inhaled heparin inhibits eicosanoid mediator production and release caused by hyperventilation with dry air, and significantly attenuates HIB.
Evaluation of the Therapeutic Potential of the Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Gefitinib in Preclinical Models of Bladder Cancer
Authors: Jose L. Dominguez-Escrig, John D. Kelly, David E. Neal, Sonya M. King, Barry R. Davies
Journal: Clinical Cancer Research (2004)

The epidermal growth factor receptor (EGFR) is associated with aggressive phenotypes and is an independent predictor of stage progression and mortality in bladder cancer. Gefitinib ('Iressa,' ZD1839) is an orally active EGFR-tyrosine kinase inhibitor. The objective of this study was to evaluate the in vitro and in vivo effects of gefitinib in the EGFR-expressing human bladder cancer cell lines 253J B-V, RT-112, and T24. EGFR expression was 3- and 2-fold higher in 253J B-V and RT-112, respectively, compared with T24 cells. Ten microm gefitinib inhibited EGFR, p42/44 extracellular signal-regulated kinase (ERK), and Akt/protein kinase B phosphorylation in all three of the cell lines. Inhibition of ERK by gefitinib was significantly greater in 253J B-V compared with RT-112 and T24 cells (9:2:1 in 253J B-V:RT-112:T24), whereas inhibition of Akt phosphorylation was less in 253J B-V compared with RT-112 and T24 cells (1:9:30 in 253J B-V:RT-112:T24). When cultured in serum-free medium supplemented with epidermal growth factor, 10 microm gefitinib inhibited DNA synthesis in T24 and RT-112 cells, whereas 1 microm gefitinib was sufficient to inhibit DNA synthesis in 253J B-V cells. Similarly, in the presence of serum, 10 microm gefitinib induced a significant reduction in S-phase and viable cell number in T24 and RT-112 cells, whereas 1-10 microm gefitinib caused a dose-dependent effect on these phenotypes in 253J B-V cells. Gefitinib significantly enhanced the ability of ionizing radiation to reduce colony forming ability in 253J B-V and RT-112 cells. In nude mice, a daily oral dose of 150 mg/kg gefitinib induced regression of tumors produced by 253J B-V cells growing at s.c. sites and suppression of tumors produced by these cells at orthotopic sites but had no effect on tumors produced by RT-112 cells growing at s.c. sites. The data indicates that gefitinib has potential therapeutic value, alone or in combination with ionizing radiation, in a subset of EGFR-expressing bladder cancers. However, there is a differential response to gefitinib in these EGFR-expressing bladder cancer cell lines. Although gefitinib can inhibit phosphorylation of EGFR, ERK, and Akt, and inhibit growth of bladder cancer cells in vitro, it does not necessarily inhibit growth of bladder cancer cells in vivo. It is likely that optimized therapy approaches will require an accurate "molecular" diagnosis allowing effective, selective, tailored therapeutic strategies to be designed.
Research pointers: Risk of subsequent thromboembolism for patients with pre-eclampsia
Authors: C. van Walraven
Journal: BMJ (2003)

artery thrombosis.These exclusions mean that the results are not strictly intention to treat, but the number of patients excluded is small (11 in total) and therefore unlikely to bias the results.As with all meta-analyses of published data, there is the potential problem of publication bias.We did a comprehensive literature search to identify published and unpublished data.It therefore seems unlikely that this would be a substantial source of bias.
DCTN1 mutations in Perry syndrome
Authors: Matthew J Farrer, Mary M Hulihan, Jennifer M Kachergus, Justus C Dächsel, A Jon Stoessl, Linda L Grantier, Susan Calne, Donald B Calne, Bernard Lechevalier, Francoise Chapon, Yoshio Tsuboi, Tatsuo Yamada, Ludwig Gutmann, Bülent Elibol, Kailash P Bhatia, Christian Wider, Carles Vilariño-Güell, Owen A Ross, Laura A Brown, Monica Castanedes-Casey, Dennis W Dickson, Zbigniew K Wszolek
Journal: Nature Genetics (2009)
Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling
Authors: Lulu Liu, Yongdong Dai, Jinna Chen, Tingting Zeng, Yan Li, Leilei Chen, Ying-Hui Zhu, Jiangchao Li, Stephanie Ma, Dan Xie, Yun-Fei Yuan, Xin-Yuan Guan
Journal: Hepatology (2013)

Amplification of 1q is one of the most frequent chromosomal alterations in human hepatocellular carcinoma (HCC). In this study we identified and characterized a novel oncogene, Maelstrom ( MAEL ), at 1q24. Amplification and overexpression of MAEL was frequently detected in HCCs and significantly associated with HCC recurrence ( P = 0.031) and poor outcome ( P = 0.001). Functional study demonstrated that MAEL promoted cell growth, cell migration, and tumor formation in nude mice, all of which were effectively inhibited when MAEL was silenced with short hairpin RNA (shRNAs). Further study found that MAEL enhanced AKT activity with subsequent GSK-3β phosphorylation and Snail stabilization, finally inducing epithelial-mesenchymal transition (EMT) and promoting tumor invasion and metastasis. In addition, MAEL up-regulated various stemness-related genes, multidrug resistance genes, and cancer stem cell (CSC) surface markers at the messenger RNA (mRNA) level. Functional study demonstrated that overexpression of MAEL increased self-renewal, chemoresistance, and tumor metastasis. Conclusion : MAEL is an oncogene that plays an important role in the development and progression of HCC by inducing EMT and enhancing the stemness of HCC. (Hepatology 2014;59:531–543)
Histologic and Clinical Characteristics Can Guide Staging Evaluations for Children and Adolescents With Rhabdomyosarcoma: A Report From the Children's Oncology Group Soft Tissue Sarcoma Committee
Authors: Aaron R. Weiss, Elizabeth R. Lyden, James R. Anderson, Douglas S. Hawkins, Sheri L. Spunt, David O. Walterhouse, Suzanne L. Wolden, David M. Parham, David A. Rodeberg, Simon C. Kao, Richard B. Womer
Journal: Journal of Clinical Oncology (2013)

To simplify the recommended staging evaluation by correlating tumor and clinical features with patterns of distant metastasis in newly diagnosed patients with embryonal rhabdomyosarcoma (ERMS) or alveolar rhabdomyosarcoma (ARMS).Patient data from the Intergroup Rhabdomyosarcoma Study Group and the Children's Oncology Group over two periods were analyzed: 1991 to 1997 and 1999 to 2004. We used recursive partitioning analyses to identify factors (including histology, age, regional nodal and distant metastatic status, tumor size, local invasiveness, and primary site) that divided patients into subsets with the most different rates of metastatic disease.Of the 1,687 patients analyzed, 5.7% had lung metastases, 4.8% had bone involvement, and 6% had bone marrow (BM) involvement. Rhabdomyosarcoma (RMS) without local invasion (T1) had a low rate of metastasis for all distant sites, especially ERMS (0% bone, 0% BM). ARMS with local invasion (T2) had a higher rate of metastasis for all distant sites (13% lung, 18% bone, 23% BM). ERMS, T2 also had a higher rate of metastatic lung involvement (9%). The likelihood of bone or BM involvement increased in the presence of lung metastases (41% with, 6% without). Regional nodal metastases (N1) predicted a high rate of metastasis in all distant sites (14% lung, 14% bone, 18% BM). A staging algorithm was developed.Staging studies in childhood RMS can be tailored to patients' presenting characteristics. Bone marrow aspirate and biopsy and bone scan are unnecessary in at least one third of patients with RMS.
Simulating gene-environment interactions in complex human diseases
Authors: Bo Peng
Journal: Genome Medicine (2010)

Because little is currently known about how genes interact with environmental factors in human diseases, and because of the large number of possible interactions between and within genetic and environmental factors, it is difficult to simulate samples for a disease caused by multiple interacting genetic and environmental factors. A recent article by Amato and colleagues in BMC Bioinformatics describes a mathematical model to characterize gene-environment interactions and a computer program that simulates them using biologically meaningful inputs. Here, I evaluate the advantages and limitations of the authors' approach in terms of its usefulness for simulating genetic samples for real-world studies of gene-environment interactions in complex human diseases.
MicroRNA-126-5p promotes endothelial proliferation and limits atherosclerosis by suppressing Dlk1
Authors: Andreas Schober, Maliheh Nazari-Jahantigh, Yuanyuan Wei, Kiril Bidzhekov, Felix Gremse, Jochen Grommes, Remco T A Megens, Kathrin Heyll, Heidi Noels, Michael Hristov, Shusheng Wang, Fabian Kiessling, Eric N Olson, Christian Weber
Journal: Nature Medicine (2014)
Induction of Immunologic Memory by Conjugated vs Plain Meningococcal C Polysaccharide Vaccine in Toddlers
Authors: N E MacDonald, S A Halperin, B J Law, B Forrest, L E Danzig, D M Granoff
Journal: JAMA (1998)

Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem.To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine.A multicenter, randomized, observer-blinded controlled trial.Urban and suburban family medicine or pediatric practices.Two hundred eleven healthy toddlers aged 15 to 23 months.Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later.IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody.In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses.Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.
Learning needs assessment: assessing the need
Authors: J. Grant
Journal: BMJ (2002)

Learning needs assessment is a crucial stage in the educational process that leads to changes in practice, and has become part of government policy for continuing professional development. Learning needs assessment can be undertaken for many reasons, so its purpose should be defined and should determine the method used and the use made of findings. Exclusive reliance on formal needs assessment could render education an instrumental and narrow process rather than a creative, professional one. Different learning methods tend to suit different doctors and different identified learning needs. Doctors already use a wide range of formal and informal ways of identifying their own learning needs as part of their ordinary practice. These should be the starting point in designing formalised educational systems for professional improvement.
Inhibitory effects of tiotropium on rhinovirus infection in human airway epithelial cells
Authors: Mutsuo Yamaya, Hidekazu Nishimura, Yukimasa Hatachi, Hiroyasu Yasuda, Xue Deng, Takahiko Sasaki, Hiroshi Kubo, Ryoichi Nagatomi
Journal: European Respiratory Journal (2012)

Infection by rhinoviruses (RVs) causes exacerbations of chronic obstructive pulmonary disease (COPD). The long-acting anti-cholinergic agent tiotropium reduces the frequency of COPD exacerbations, but the inhibitory effects of tiotropium on the COPD exacerbations induced by RVs are unclear. Likewise, the effects of tiotropium on RVs infection remain to be studied. To examine the effects of tiotropium on RV infection and RV infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group RV, type 14 RV (RV14). RV14 infection increased the viral titre and the amount of pro-inflammatory cytokines, including interleukin (IL)-1β and -6, in supernatant fluids and the amount of RV14 RNA in cells. Tiotropium reduced RV14 titres, RNA and cytokine concentrations, and susceptibility to RV14 infection. Tiotropium reduced the expression of intercellular adhesion molecule (ICAM)-1, the receptor for RV14, and the number of cellular acidic endosomes, which allow RV14 RNA to enter the cytoplasm. Tiotropium inhibited the activation of nuclear factor- κ B proteins, including p50 and p65, in the nuclear extracts, and it increased the cytosolic amount of inhibitory κB-α. Tiotropium may inhibit RV14 infection by reducing the levels of ICAM-1 and acidic endosomes and may also modulate airway inflammation in rhinovirus infection.