tbuckley/cabot-search huggingface dataset:
Prions in the Urine of Patients with Variant Creutzfeldt–Jakob Disease
Authors: Fabio Moda, Pierluigi Gambetti, Silvio Notari, Luis Concha-Marambio, Marcella Catania, Kyung-Won Park, Emanuela Maderna, Silvia Suardi, Stéphane Haïk, Jean-Philippe Brandel, James Ironside, Richard Knight, Fabrizio Tagliavini, Claudio Soto
Journal: New England Journal of Medicine (2014)

Prions, the infectious agents responsible for transmissible spongiform encephalopathies, consist mainly of the misfolded prion protein (PrPSc). The unique mechanism of transmission and the appearance of a variant form of Creutzfeldt–Jakob disease, which has been linked to consumption of prion-contaminated cattle meat, have raised concerns about public health. Evidence suggests that variant Creutzfeldt–Jakob disease prions circulate in body fluids from people in whom the disease is silently incubating.
CCR4 ligands are up-regulated in the airways of atopic asthmatics after segmental allergen challenge
Authors: C. Pilette, J.N. Francis, S.J. Till, S.R. Durham
Journal: European Respiratory Journal (2004)

T-helper (Th) 2 cytokines are thought to mediate most features of allergic inflammation in atopic asthma. However, it remains unclear whether chemokine pathways direct selective recruitment of Th2 cells to the airways during human allergic responses. Bronchoalveolar lavage (BAL) was performed in 15 nonsmoking mild atopic asthmatics before and 24 h after a fibreoptic segmental allergen challenge, and chemokines related to T-cell recruitment were assayed by ELISA. The Th2-related C-C chemokine (CCR)4 ligands, macrophage-derived chemokine/C-C chemokine ligand (CCL)22 and thymus and activation-regulated chemokine/CCL17, were increased in BAL after challenge. These chemokines correlated significantly with lymphocyte numbers and with interleukin (IL)‐5 and IL‐13 in post-challenge BAL. In contrast, two out of three putative Th1-related chemokines did not change. There were no alterations in monokine induced by interferon (IFN)‐γ/CXC chemokine ligand (CXCL)9 or macrophage inflammatory protein‐1α/CCL3; whereas a significant increase in IFN-induced protein-10kDa/CXCL10 was observed, which did not correlate with the T-cell influx. In peripheral mononuclear cells from atopic donors, CCL22 and CCL17 were induced by IL‐4 and IL‐13, further supporting the relationship between CCL22/CCL17 and Th2 cytokines. Finally, CCL22 was able to trigger actin polymerisation in peripheral CD4+ T-cells expressing CCR4. Thus, C-C chemokine receptor 4 ligands are up-regulated in the airways of atopic asthmatics following allergen exposure, contribute to the T-cell influx to the airways and are closely related to the Th2-cytokine response.
Requirement of Interleukin 17 Receptor Signaling for Lung Cxc Chemokine and Granulocyte Colony-Stimulating Factor Expression, Neutrophil Recruitment, and Host Defense
Authors: Peng Ye, Fred H. Rodriguez, Suzanne Kanaly, Kim L. Stocking, Jill Schurr, Paul Schwarzenberger, Peter Oliver, Weitao Huang, Ping Zhang, Jason Zhang, Judd E. Shellito, Greg J. Bagby, Steve Nelson, Keith Charrier, Jacques J. Peschon, Jay K. Kolls
Journal: The Journal of Experimental Medicine (2001)

Bacterial pneumonia is an increasing complication of HIV infection and inversely correlates with the CD4(+) lymphocyte count. Interleukin (IL)-17 is a cytokine produced principally by CD4(+) T cells, which induces granulopoiesis via granulocyte colony-stimulating factor (G-CSF) production and induces CXC chemokines. We hypothesized that IL-17 receptor (IL-17R) signaling is critical for G-CSF and CXC chemokine production and lung host defenses. To test this, we used a model of Klebsiella pneumoniae lung infection in mice genetically deficient in IL-17R or in mice overexpressing a soluble IL-17R. IL-17R-deficient mice were exquisitely sensitive to intranasal K. pneumoniae with 100% mortality after 48 h compared with only 40% mortality in controls. IL-17R knockout (KO) mice displayed a significant delay in neutrophil recruitment into the alveolar space, and had greater dissemination of K. pneumoniae compared with control mice. This defect was associated with a significant reduction in steady-state levels of G-CSF and macrophage inflammatory protein (MIP)-2 mRNA and protein in the lung in response to the K. pneumoniae challenge in IL-17R KO mice. Thus, IL-17R signaling is critical for optimal production of G-CSF and MIP-2 and local control of pulmonary K. pneumoniae infection. These data support impaired IL-17R signaling as a potential mechanism by which deficiency of CD4 lymphocytes predisposes to bacterial pneumonia.
Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody.
Authors: G Kraal, M Breel, M Janse, G Bruin
Journal: The Journal of Experimental Medicine (1986)

An mAb, NLDC-145, is described that specifically reacts with a group of nonlymphoid dendritic cells including Langerhans cells (LC), veiled cells (VC), and interdigitating cells (IDC). The antibody does not react with precursor cells in bone marrow and blood. Macrophages are not stained by the antibody, but a subpopulation of Ia+ peritoneal exudate cells is recognized. Possible relationships of the various nonlymphoid dendritic cell (NLDC) types are discussed.
Universal influenza vaccination in the elderly: another piece in the jigsaw
Authors: Z. Borrill, M. Woodhead
Journal: European Respiratory Journal (2007)

It is widely accepted that influenza causes significant mortality and morbidity in the elderly population during winter epidemics. Annual vaccination is recommended in the majority of western countries for all adults aged >65 yrs. Vaccination is aimed not at prevention of the spread of influenza, most of which occurs in children and younger adults, but at reduction of the complications among those who are most vulnerable, with death being the most significant, potentially preventable, complication. Each year, considerable resources are devoted to the creation of a vaccine against the influenza strains expected to be most prevalent, and to its timely administration. Despite the widespread endorsement of influenza vaccination for the elderly, its overall effectiveness continues to be debated.

Measuring the number of excess deaths attributable to influenza is difficult. Influenza-like illness (ILI) caused by other viruses is common and rarely distinguishable from influenza, due to a lack of virological conformation. Furthermore, influenza contributes to deaths from many causes which may not be recorded as such, the so called “hidden deaths”. In developed countries, mortality is highest during the winter months, coinciding temporally with the existence of influenza epidemics. …
Accurate Measurement of Left Ventricular Ejection Fraction by Three-dimensional Echocardiography
Authors: Youssef F.M. Nosir, Paolo M. Fioretti, Wim B. Vletter, Eric Boersma, Alessandro Salustri, Joyce Tjoa Postma, Ambroos E.M. Reijs, Folkert J. Ten Cate, Jos R.T.C. Roelandt
Journal: Circulation (1996)

Background Three-dimensional echocardiography is a promising technique for calculation of left ventricular ejection fraction, because it allows its measurement without geometric assumptions. However, few data exist that study its reproducibility and accuracy in patients. Methods and Results Twenty-five patients underwent radionuclide angiography and three-dimensional echocardiography that used the rotational technique (2° interval and ECG and respiratory gating). Left ventricular volume and ejection fraction were calculated by use of Simpson's rule at a slice thickness of 3 mm. Analyses were performed to define the largest slice thickness required for accurate calculation of left ventricular volume and ejection fraction. Three-dimensional echocardiography showed excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction (mean±SD, 38.9±19.8 and 38.5±18.0, respectively; r =.99); their mean difference was not significant (0.03±0.17; P =.3), and they had a close limit of agreement (−0.385, 0.315). Intraobserver variability for radionuclide angiography and three-dimensional echocardiography was 4.2% and 2.6%, respectively, whereas interobserver variability was 6.2% and 5.3%, respectively. There was no significant difference between left ventricular volume and ejection fraction calculated at a slice thickness of 3 mm and that calculated at different slice thicknesses up to 24 mm. However, the standard deviation of the mean difference showed a stepwise increase, particularly at thicknesses &gt;15 mm. At a slice thickness of 15 mm, the probability of three-dimensional echocardiography to detect ≥6% difference in ejection fraction was 80%. Conclusions Three-dimensional echocardiography has excellent correlation with radionuclide angiography for calculation of left ventricular ejection fraction in patients and has an observer variability similar to that of radionuclide angiography. We recommend the use of a 15-mm-thick slice for accurate and rapid measurement of left ventricular volume and ejection fraction.
High-Dose [<sup>131</sup>I]Tositumomab (anti-CD20) Radioimmunotherapy and Autologous Hematopoietic Stem-Cell Transplantation for Adults ≥ 60 Years Old With Relapsed or Refractory B-Cell Lymphoma
Authors: Ajay K. Gopal, Joseph G. Rajendran, Ted A. Gooley, John M. Pagel, Darrell R. Fisher, Stephen H. Petersdorf, David G. Maloney, Janet F. Eary, Frederick R. Appelbaum, Oliver W. Press
Journal: Journal of Clinical Oncology (2007)

The majority of patients with relapsed or refractory B-cell non-Hodgkin's lymphoma (NHL) are older than 60 years, yet they are often denied potentially curative high-dose therapy and autologous stem-cell transplantations (ASCT) because of the risk of excessive treatment-related morbidity and mortality. Myeloablative anti-CD20 radioimmunotherapy (RIT) can deliver curative radiation doses to tumor sites while limiting exposure to normal organs and may be particularly suited for older adults requiring high-dose therapy.Patients older than 60 years with relapsed B-cell NHL (B-NHL) received infusions of tositumomab anti-CD20 antibody labeled with 185 to 370 Mbq (5 to 10 mCi) [131I]-tracer for dosimetry purposes followed 10 days later by individualized therapeutic infusions of [131I]tositumomab (median, 19.4 Gbq [525 mCi]; range, 12.1 to 42.7 Gbq [328 to 1,154 mCi]) to deliver 25 to 27 Gy to the critical normal organ receiving the highest radiation dose. ASCT was performed approximately 2 weeks after therapy.Twenty-four patients with a median age of 64 years (range, 60 to 76 years), who had received a median of four prior regimens (range, two to 14 regimens), were treated. Thirteen patients (54%) had chemotherapy-resistant disease. The estimated 3-year overall and progression-free survival rates were 59% and 51%, respectively, with a median follow-up of 2.9 years (range, 1 to 6 years). All patients experienced expected myeloablation with engraftment of platelets (> or = 20 K/microL) and neutrophils ( 500/microL), occurring at a median of 9 and 15 days after ASCT, respectively. There were no treatment-related deaths, and only two patients experienced grade 4 nonhematologic toxicity.Myeloablative RIT and ASCT is a safe and effective therapeutic option for older adults with relapsed B-NHL.
Missing elements of modern management
Authors: W J Fawcett, J T Lordon, N F Quiney, N D Karanjia, T A Rockall
Journal: BMJ (2007)

Ballinger and Anggiansah's review of the management of colorectal cancer made little or no mention of important aspects of current treatment.1

They did not mention the role of laparoscopic large bowel resection for colorectal cancers, which has become increasingly widely …
The discovery value of “Big Science”
Authors: José Esparza, Tadataka Yamada
Journal: The Journal of Experimental Medicine (2007)

The increasing complexity of biomedical research is leading to the exploration of new models for large-scale collaborative research. This Big Science approach, however, has created anxieties and potential tensions between investigator-driven research, and research guided by a more organized, collaborative effort. Another potential tension exists between research conducted purely in search of new knowledge and research aimed at finding solutions. We argue that big biomedicine--the work of coordinated multidisciplinary groups that use the latest technologies to solve complex problems--can be an important way to harness the creativity of individual investigators, stimulate innovation, and supply the infrastructure, experimental systems, and resources needed to solve the urgent health problems confronted by our global society. We discuss this using the example of the Global HIV Vaccine Enterprise.
Contribution of Nitric Oxide Synthases 1, 2, and 3 to Airway Hyperresponsiveness and Inflammation in a Murine Model of Asthma
Authors: George T. De Sanctis, James A. MacLean, Kaoru Hamada, Sanjay Mehta, Jeremy A. Scott, Aiping Jiao, Chandri N. Yandava, Lester Kobzik, Walter W. Wolyniec, Attila J. Fabian, Changaram S. Venugopal, Hartmut Grasemann, Paul L. Huang, Jeffrey M. Drazen
Journal: The Journal of Experimental Medicine (1999)

Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.
<i>EGR1</i> Predicts <i>PTEN</i> and Survival in Patients With Non–Small-Cell Lung Cancer
Authors: Bernadette Ferraro, Gerold Bepler, Swati Sharma, Alan Cantor, Eric B. Haura
Journal: Journal of Clinical Oncology (2005)

The zinc finger transcription factor early growth response gene 1 (EGR1) is underexpressed in non-small-cell lung cancer (NSCLC) compared with normal lung. EGR1 expression has been linked to tumor suppression as a result of cell cycle arrest and apoptosis through regulation of tumor suppressor pathways including PTEN. For these reasons, we hypothesized that reduced levels of EGR1 would correlate with inferior outcome in patients with NSCLC.Patients who underwent surgical resection for NSCLC had RNA extracted from tumor tissue and EGR1 gene expression was quantified by real-time quantitative polymerase chain reaction. The levels of EGR1 expression were examined in relationship to patient characteristics, histology, tumor stage, PTEN expression, and overall and disease-free survival.EGR1 expression strongly correlated with PTEN expression (P < .0001). No correlation of EGR1 with histology or stage was detected. Patients with high levels of EGR1 had better overall and disease-free survival compared with patients with low levels of EGR1 (P = .040 and P = .096, respectively). In a stratified log-rank test, low EGR1 expression was predictive of poor survival independent of tumor stage.EGR1 gene expression predicts PTEN levels and survival after surgical resection of NSCLC. Consistent with its known tumor suppressor properties, lower levels of EGR1 are associated with poor outcome. Identification of patients with low EGR1 therefore may identify patients at high risk for disease recurrence and may also identify patients who have tumors resistant to therapy secondary to loss of pathways such as PTEN.
Cancer-Stimulated Mesenchymal Stem Cells Create a Carcinoma Stem Cell Niche via Prostaglandin E2 Signaling
Authors: Hua-Jung Li, Ferenc Reinhardt, Harvey R. Herschman, Robert A. Weinberg
Journal: Cancer Discovery (2012)

Mesenchymal cells of the tumor-associated stroma are critical determinants of carcinoma cell behavior. We focus here on interactions of carcinoma cells with mesenchymal stem cells (MSC), which are recruited to the tumor stroma and, once present, are able to influence the phenotype of the carcinoma cells. We find that carcinoma cell-derived interleukin-1 (IL-1) induces prostaglandin E(2) (PGE(2)) secretion by MSCs. The resulting PGE(2) operates in an autocrine manner, cooperating with ongoing paracrine IL-1 signaling, to induce expression of a group of cytokines by the MSCs. The PGE(2) and cytokines then proceed to act in a paracrine fashion on the carcinoma cells to induce activation of β-catenin signaling and formation of cancer stem cells. These observations indicate that MSCs and derived cell types create a cancer stem cell niche to enable tumor progression via release of PGE(2) and cytokines.Although PGE2 has been implicated time and again in fostering tumorigenesis, its effects on carcinoma cells that contribute specifically to tumor formation are poorly understood. Here we show that tumor cells are able to elicit a strong induction of the COX-2/microsomal prostaglandin-E synthase-1 (mPGES-1)/PGE(2) axis in MSCs recruited to the tumor-associated stroma by releasing IL-1, which in turn elicits a mesenchymal/stem cell–like phenotype in the carcinoma cells.
British Hypertension Society guidelines for hypertension management 1999: summary
Authors: L. E Ramsay, B. Williams, G D. Johnston, G. A MacGregor, L. Poston, J. F Potter, N. R Poulter, G. Russell
Journal: BMJ (1999)

This article summarises the new British Hypertension Society guidelines for management of hypertension, which have been published in full.1 Since the previous guidelines 2 3 much new evidence has emerged on optimal blood pressure targets4; management of hypertension in diabetic patients4–7; treatment of isolated systolic hypertension8; comparison of the antihypertensive efficacy and tolerability of different drug classes9–11; the role of non-pharmacological measures for prevention 12 13 and treatment of hypertension14; and additional benefits associated with the use of aspirin and statins.

Of concern is that national surveys continue to reveal incomplete detection, treatment, and control of hypertension.15 Furthermore, treated hypertensive patients still die prematurely from cardiovascular disease.16 These guidelines aim to present the best currently available evidence on hypertension management and their implementation.

#### Summary points

Use non-pharmacological measures in all hypertensive and borderline hypertensive people

Initiate antihypertensive drug treatment in people with sustained systolic blood pressure ≥160 mm Hg or sustained diastolic blood pressure ≥100 mm Hg

Decide on treatment in people with sustained systolic blood pressure between 140 and 159 mm Hg or sustained diastolic blood pressure between 90 and 99 mm Hg according to the presence or absence of target organ damage, cardiovascular disease, diabetes, or a 10 year coronary heart disease risk ≥15% according to the Joint British Societies coronary heart disease risk assessment programme or risk chart

Optimal blood pressure treatment targets are systolic blood pressure <140 mm Hg and diastolic blood pressure <85 mm Hg; the minimum acceptable level of control (audit standard) recommended is <150/<90 mm Hg

In the absence of contraindications or compelling indications for other antihypertensive agents, low dose thiazide diuretics or β blockers are preferred as first line treatment for the majority of hypertensive people; compelling …
Economic evaluation favours physiotherapy but not corticosteroid injection as a first-line intervention for chronic lateral epicondylalgia: evidence from a randomised clinical trial
Authors: Brooke K Coombes, Luke Connelly, Leanne Bisset, Bill Vicenzino
Journal: British Journal of Sports Medicine (2015)

To determine the cost-effectiveness of corticosteroid injection, physiotherapy and a combination of these interventions, compared to a reference group receiving a blinded placebo injection.165 adults with unilateral lateral epicondylalgia of longer than 6 weeks duration from Brisbane, Australia, were randomised for concealed allocation to saline injection (placebo), corticosteroid injection, saline injection plus physiotherapy (eight sessions of elbow manipulation and exercise) or corticosteroid injection plus physiotherapy. Costs to society and health-related quality of life (estimated by EuroQol-5D) over the 1 year follow-up were used to generate incremental cost per quality-adjusted life year (QALY) ratios for each intervention relative to placebo.Intention-to-treat analysis was possible for 154 (93%) of trial participants. Physiotherapy was more costly, but was the only intervention that produced a statistically significant improvement in quality of life relative to placebo (MD, 95% CI 0.035, 0.003 to 0.068). Similar cost/QALY ratios were found for physiotherapy ($A29 343; GBP18 962) and corticosteroid injection ($A31 750; GBP20 518); however, the probability of being more cost-effective than placebo at values above $A50 000 per quality-adjusted life year was 81% for physiotherapy and 53% for corticosteroid injection. Cost/QALY was far greater for a combination of corticosteroid injection and physiotherapy ($A228 000; GBP147 340).Physiotherapy was a cost-effective treatment for lateral epicondylalgia. Corticosteroid injection was associated with greater variability, and a lower probability of being cost-effective if a willingness to pay threshold of $A50 000 is assumed. A combination of corticosteroid injection and physiotherapy was ineffective and cost-ineffective. Physiotherapy, not corticosteroid injection, should be considered as a first-line intervention for lateral epicondylalgia.anzctr.org Trial identifier: ACTRN12609000051246.