tbuckley/cabot-search huggingface dataset:
Molecular signatures of neurodegeneration in the cortex of PS1/PS2 double knockout mice
Authors: Károly Mirnics, Eric M Norstrom, Krassimira Garbett, Se Choi, Xiaoqiong Zhang, Philip Ebert, Sangram S Sisodia
Journal: Molecular Neurodegeneration (2008)

Familial Alzheimer's disease-linked variants of presenilin (PSEN1 and PSEN2) contribute to the pathophysiology of disease by both gain-of-function and loss-of-function mechanisms. Deletions of PSEN1 and PSEN2 in the mouse forebrain result in a strong and progressive neurodegenerative phenotype which is characterized by both anatomical and behavioral changes. To better understand the molecular changes associated with these morphological and behavioral phenotypes, we performed a DNA microarray transcriptome profiling of the hippocampus and the frontal cortex of the PSEN1/PSEN2 double knock-out mice and littermate controls at five different ages ranging from 2–8 months. Our data suggest that combined deficiencies of PSEN1 and PSEN2 results in a progressive, age-dependent transcriptome signature related to neurodegeneration and neuroinflammation. While these events may progress differently in the hippocampus and frontal cortex, the most critical expression signatures are common across the two brain regions, and involve a strong upregulation of cathepsin and complement system transcripts. The observed neuroinflammatory expression changes are likely to be causally linked to the neurodegenerative phenotype observed in mice with compound deletions of PSEN1 and PSEN2. Furthermore, our results suggest that the evaluation of inhibitors of PS/γ-secretase activity for treatment of Alzheimer's Disease must include close monitoring for signs of calpain-cathepsin system activation.
Evidence inconsistent with a role for the Bcg gene (Nramp1) in resistance of mice to infection with virulent Mycobacterium tuberculosis.
Authors: E Medina, R J North
Journal: The Journal of Experimental Medicine (1996)

The superior resistance of some strains of mice over others to infection with certain intracellular pathogens, including the vaccine strain of Mycobacterium bovis, bacillus Calmette Guerin (BCG), is determined by a gene associated with a small segment of chromosome 1 designated by Ity/Lsh/Bcg locus, referred to here as the Bcg locus. DBA/2 mice containing the dominant resistant allele of the Bcg gene (Bcgr), major histocompatibility complex-compatible BALB/c mice containing the recessive susceptible allele (Bcgs), and congenic C.D2-N20 Bcgr, which are genetically the same as BALB/c mice except for possessing a small piece of DBA/2 chromosome 1 containing the Bcg locus, were used to determine whether the Bcg gene determines resistance to infection with the virulent H37Rv strain of Mycobacterium tuberculosis (Mtb). According to the survival times of Bcgr and Bcgs mice infected via either the intravenous or respiratory route, Bcgr mice proved much less, rather than more, resistant to Mtb infection than Bcgs mice. Shorter survival times of Bcgr mice were associated with an inferior capacity to control Mtb growth in their lungs and to retard the development of Mtb-induced pathology in this organ. Resistance to Mtb infection was a dominant trait in the F1 progeny of Bcgr and Bcgs mice. The results show that resistance to Mtb is not determined by the resistance allele of the Bcg gene nor by the recently isolated candidate Bcg gene Nramp1, located in the Bcg locus.
MANAGEMENT OF EARLY NEPHROPATHY IN DIABETIC PATIENTS
Authors: Carl Erik Mogensen, M.D
Journal: Annual Review of Medicine (1995)

▪ Abstract Diabetic patients go through several stages of renal disease, moving from normo- to micro- to macroalbuminuria. Good metabolic control can prevent or postpone the development of microalbuminuria, the earliest sign of diabetic renal disease. Thus, efforts should focus on obtaining the best possible control before the onset of microalbuninuria. In patients with microalbuminuria, blood pressure starts to increase, and early antihypertensive treatment becomes important. Good glycemic control may be difficult to achieve. With overt nephropathy, defined as clinical proteinuria, a relentless decline in glomerular filtration rate (GFR) occurs unless patients are carefully treated with antihypertensive agents. Protein restriction may also be necessary, but a clear beneficial effect of optimized diabetes care is difficult to document. Early screening is recommended, with an emphasis on testing for albuminuria, including microalbuminuria, along with careful control of blood pressure.
A Randomized Phase 2 Study of Erlotinib Plus Pemetrexed vs Erlotinib or Pemetrexed Alone as Second-Line Treatment for Never-Smoker Patients with Non-Squamous Advanced Non-Small Cell Lung Cancer (NSCLC)
Authors: D.H. Lee, J.S. Lee, S.W. Kim, J. Rodrigues Pereira, B. Han, X.Q. Song, J. Wang, H.-K. Kim, T.P. Sahoo, R. Digumarti, X. Wang, S. Altug, M. Orlando
Journal: Annals of Oncology (2012)
Use of Flow–Volume Curves to Predict Oral Appliance Treatment Outcome in Obstructive Sleep Apnea
Authors: Biao Zeng, Andrew T. Ng, M. Ali Darendeliler, Peter Petocz, Peter A. Cistulli
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

It has been recognized that mandibular advancement splint (MAS) treatment is effective in some, but not all, patients with obstructive sleep apnea (OSA). Hence there is a need for a simple and reliable clinical tool to assist in the differentiation of treatment responses. We hypothesized that abnormalities of flow-volume curves, together with other clinical variables, may have clinical utility in the prediction of MAS treatment outcome.Fifty-four patients with known OSA underwent MAS treatment. Expiratory and inspiratory flow-volume curves were measured in the erect and supine positions to derive midinspiratory flow (MIF(50)) and the ratio of expiratory to inspiratory flow at 50% of vital capacity (MEF(50):MIF(50)). Multivariable logistic regression was performed to identify additional significant clinical variables in the prediction of treatment outcome.The mean (+/- SD) apnea-hypopnea index (AHI) in 35 responders was significantly reduced from 28.9 +/- 13.7 to 6.7 +/- 5.8/hour (p<0.001). In 19 nonresponders there was no significant change in AHI. MIF(50) was lower (6.04 +/- 1.80 vs. 6.88 +/- 1.08 L/second; p=0.035) and the MEF(50):MIF(50) ratio was higher (0.82 +/- 0.23 vs. 0.61 +/- 0.15; p=0.001) in responders than nonresponders. Logistic regression analysis revealed that the MEF(50):MIF(50) ratio was the most important predictive factor for MAS treatment outcome, but that body mass index, age, and baseline AHI were also contributory.These data suggest that flow-volume curves, in combination with other factors such as body mass index, age, and baseline AHI, may have a useful clinical role in the prediction of treatment outcome with MAS.
Diabetes TV News Coverage Lags Behind
Authors: Stephania T. Miller, Marquita N. Campbell, James W. Pichert
Journal: Diabetes Care (2002)

Millions of Americans depend on the national nightly network news programs for current events information (1). Previous studies showed that nightly network news coverage about diabetes paled in comparison with that given to cancer and heart disease during the 1970s and 1980s (2,3). We evaluated whether the amount of national news coverage given to diabetes had improved during the 1990s and the extent to which racial disparities in diabetes had been highlighted. Specific objectives included tracking diabetes-related coverage on major nightly network news programs for the last 10 years, comparing diabetes coverage with that of cancer and heart disease, and examining the content of diabetes-related coverage.

The Vanderbilt Television News Archives (VTNA) has videotaped, catalogued, and indexed nightly news broadcasts from ABC, CBS, and NBC since 1968 (4). In addition, the VTNA …
Imaging Androgen Receptor Signaling with a Radiotracer Targeting Free Prostate-Specific Antigen
Authors: David Ulmert, Michael J. Evans, Jason P. Holland, Samuel L. Rice, John Wongvipat, Kim Pettersson, Per-Anders Abrahamsson, Peter T. Scardino, Steven M. Larson, Hans Lilja, Jason S. Lewis, Charles L. Sawyers
Journal: Cancer Discovery (2012)

Abstract Despite intense efforts to develop radiotracers to detect cancers or monitor treatment response, few are widely used as a result of challenges with demonstrating clear clinical use. We reasoned that a radiotracer targeting a validated clinical biomarker could more clearly assess the advantages of imaging cancer. The virtues and shortcomings of measuring secreted prostate-specific antigen (PSA), an androgen receptor (AR) target gene, in patients with prostate cancer are well documented, making it a logical candidate for assessing whether a radiotracer can reveal new (and useful) information beyond that conferred by serum PSA. Therefore, we developed 89Zr-labeled 5A10, a novel radiotracer that targets “free” PSA. 89Zr–5A10 localizes in an AR-dependent manner in vivo to models of castration-resistant prostate cancer, a disease state in which serum PSA may not reflect clinical outcomes. Finally, we demonstrate that 89Zr–5A10 can detect osseous prostate cancer lesions, a context where bone scans fail to discriminate malignant and nonmalignant signals. Significance: This report establishes that AR-dependent changes in PSA expression levels can be quantitatively measured at tumor lesions using a radiotracer that can be rapidly translated for human application and advances a new paradigm for radiotracer development that may more clearly highlight the unique virtues of an imaging biomarker. Cancer Discov; 2(4); 320–7. ©2012 AACR. Read the Commentary on this article by Herschman and Czernin, p. 301 This article is highlighted in the In This Issue feature, p. 288
Synthesis of leukotriene C and other arachidonic acid metabolites by mouse pulmonary macrophages.
Authors: C A Rouzer, W A Scott, A L Hamill, Z A Cohn
Journal: The Journal of Experimental Medicine (1982)

Mouse resident pulmonary macrophages were subdivided into alveolar (PAM) and interstitial (PTM) populations on the basis of accessibility to pulmonary lavage, and zymosan-induced arachidonic acid (20:4) metabolism was examined in both populations labeled with [3H]20:4. Maximal phagocytic doses of unopsonized zymosan induced the specific release of 11% of phospholipid 20:4 by PTM and 4.6% by PAM. Direct fatty acid analysis of [3H]20:4-labeled PTM cultured in the presence or absence of zymosan indicated that the specific activity of the [3H]20:4 in cell phospholipid provided an accurate measure of 20:4 released by the cells, and could therefore be used to quantitate the synthesis of 20:4 metabolites by PTM in vitro. The single major 20:4 metabolite of PTM was the slow-reacting substance leukotriene C, which was synthesized in quantities of 3-4 pmol/microgram cell protein (280-370 pmol/10(6) cells), and comprised 20-25% of the released 20:4. PTM also synthesized prostaglandin E2, prostacyclin, thromboxane A2, and hydroxyeicosatetraenoic acids. In contrast, PAM produced leukotrienes D and E in addition to leukotriene C, prostaglandin E2, thromboxane A2, and hydroxyeicosatetraenoic acids. Prostacyclin formation by PAM was not observed. These studies define a set of experimental conditions for the study of 20:4 metabolism by pulmonary macrophages, and demonstrate that these cells are rich sources of LTC as well as other 20:4 oxygenated products.
Efficacy and safety of belimumab in primary Sjögren's syndrome: results of the BELISS open-label phase II study
Authors: Xavier Mariette, Raphaèle Seror, Luca Quartuccio, Gabriel Baron, Sara Salvin, Martina Fabris, Frederic Desmoulins, Gaétane Nocturne, Philippe Ravaud, Salvatore De Vita
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Increased expression of B cell activating factor (BAFF or B lymphocyte stimulator) may explain the B cell activation characteristic of primary Sjögren9s syndrome (pSS). <h3>Objectives</h3> To evaluate the efficacy and safety of belimumab, targeting BAFF, in patients with pSS. <h3>Methods</h3> Patients were included in this bi-centric prospective 1-year open-label trial if they fulfilled American European Consensus group criteria, were anti-Sjögren9s syndrome A-positive and had current systemic complications or salivary gland enlargement, or early disease (&lt;5 years), or biomarkers of B cell activation. They received belimumab, 10 mg/kg, at weeks 0, 2 and 4 and then every 4 weeks to week 24. The primary end-point, assessed at week 28, was improvement in two of five items: reduction in ≥30% in dryness score on a visual analogue scale (VAS), ≥30% in fatigue VAS score, ≥30% in VAS pain score, ≥30% in systemic activity VAS assessed by the physician and/or &gt;25% improvement in any B cell activation biomarker values. <h3>Results</h3> Among 30 patients included, the primary end-point was achieved in 18 (60%). The mean (SD) European League Against Rheumatism (EULAR) Sjögren9s Syndrome Disease Activity Index decreased from 8.8 (7.4) to 6.3 (6.6) (p=0.0015) and EULAR) Sjögren9s Syndrome Patient Reported Index from 6.4 (1.1) to 5.6 (2.0) (p=0.0174). The mean dryness, fatigue and pain VAS varied from 7.8 (1.8) to 6.2 (2.9) (p=0.0021), 6.9 (1.8) to 6.0 (2.2) (p=0.0606) and 4.6 (2.6) to 4.7 (2.4) (p=0.89), respectively. Salivary flow and Schirmer9s test did not change. <h3>Conclusions</h3> These encouraging results justify future randomised controlled trials of belimumab in a selected target population of pSS patients most likely to benefit from treatment.
Heart-Infiltrating Prominin-1 <sup>+</sup> /CD133 <sup>+</sup> Progenitor Cells Represent the Cellular Source of Transforming Growth Factor β–Mediated Cardiac Fibrosis in Experimental Autoimmune Myocarditis
Authors: Gabriela Kania, Przemyslaw Blyszczuk, Sokrates Stein, Alan Valaperti, Davide Germano, Stephan Dirnhofer, Lukas Hunziker, Christian M. Matter, Urs Eriksson
Journal: Circulation Research (2009)

Rationale : Myocardial fibrosis is a hallmark of inflammation-triggered end-stage heart disease, a common cause of heart failure in young patients. Objective : We used CD4 + T-cell–mediated experimental autoimmune myocarditis model to determine the parameters regulating cardiac fibrosis in inflammatory heart disease. Methods and Results : α-Myosin heavy chain peptide/complete Freund’s adjuvant immunization was used to induce experimental autoimmune myocarditis in BALB/c mice. Chimeric mice, reconstituted with enhanced green fluorescence protein (EGFP) + bone marrow, were used to track the fate of inflammatory cells. Prominin-1 + cells were isolated from the inflamed hearts, cultured in vitro and injected intracardially at different stages of experimental autoimmune myocarditis. Transforming growth factor (TGF)-β–mediated fibrosis was addressed using anti–TGF-β antibody treatment. Myocarditis peaked 21 days after immunization and numbers of cardiac fibroblasts progressively increased on follow-up. In chimeric mice, &gt;60% of cardiac fibroblasts were EGFP + 46 days after immunization. At day 21, cardiac infiltrates contained ≈30% of prominin-1 + progenitors. In vitro and in vivo experiments confirmed that prominin-1 + but not prominin-1 − cells isolated from acutely inflamed hearts represented the cellular source of cardiac fibroblasts at late stages of disease, characterized by increased TGF-β levels within the myocardium. Mechanistically, the in vitro differentiation of heart-infiltrating prominin-1 + cells into fibroblasts depended on TGF-β–mediated phosphorylation of Smad proteins. Accordingly, anti–TGF-β antibody treatment prevented myocardial fibrosis in immunized mice. Conclusions : Taken together, heart-infiltrating prominin-1 + progenitors are the major source of subsequent TGF-β–triggered cardiac fibrosis in experimental autoimmune myocarditis. Recognizing the critical, cytokine-dependent role of bone marrow–derived progenitors in cardiac remodeling might result in novel treatment concepts against inflammatory heart failure.
β-ADRENERGIC RECEPTORS AND RECEPTOR SIGNALING IN HEART FAILURE
Authors: Steven R. Post, H. Kirk Hammond, Paul A. Insel
Journal: The Annual Review of Pharmacology and Toxicology (1999)

▪ Abstract Cardiac β-adrenergic receptors, which respond to neuronally released and circulating catecholamines, are important regulators of cardiac function. Congestive heart failure, a common clinical condition, is associated with a number of alterations in the activation and deactivation of β-adrenergic receptor pathways. Studies with failing hearts from humans and animals indicate that such alterations include changes in the expression or function of β-adrenergic receptors, G-proteins, adenylyl cyclases, and G-protein receptor kinases. The net effect of these alterations is the substantial blunting of β-adrenergic receptor-mediated cardiac response. An important unanswered question is whether the loss of cardiac β-adrenergic receptor responsiveness is a contributing cause, or a result, of ventricular dysfunction. Even though this question remains unanswered, the concept of targeting the β-adrenergic pathway in the failing heart is becoming increasingly popular and several new therapeutic strategies are in development.
THE RÔLE OF THE RETICULO-ENDOTHELIAL SYSTEM IN IMMUNITY
Authors: C. W. Jungeblut
Journal: The Journal of Experimental Medicine (1927)

1. The minimum amount of diphtheria toxin which killed normal mice of from 24 to 30 gm. in weight upon intravenous injection, was found to be between 75 and 100 times the M.F.D. for the guinea pig. When given intraperitoneally, the fatal dose for mice was as high as 200 M.F.D. 2. There was no significant difference in the lethal action of diphtheria toxin for normal mice and mice in which an elimination of the reticulo-endothelial system had been attempted by means of blocking injections of India ink, or splenectomy, or a combination of both operations. 3. Attempts to infect normal mice and mice treated as described with large doses of a highly virulent diphtheria strain were unsuccessful with both groups of animals.
Accumulation of Foxp3+ T Regulatory Cells in Draining Lymph Nodes Correlates with Disease Progression and Immune Suppression in Colorectal Cancer Patients
Authors: Liufu Deng, Haizeng Zhang, Yan Luan, Jianfeng Zhang, Qiao Xing, Shuxiao Dong, Xiaoran Wu, Mingyue Liu, Shengdian Wang
Journal: Clinical Cancer Research (2010)

To assess the relation of Foxp3(+) regulatory T cells (Treg) in tumor draining lymph nodes (TDLNs) with tumor progression and immune suppression in colorectal cancer (CRC).Flow cytometry was used to analyze the densities of Tregs in lymphocytes of TDLNs, peripheral blood, and tumors from 34 patients with CRC. The frequency of Tregs was compared and evaluated for the association with disease stage. The effect of Tregs on the function of CD8(+) T cells was investigated by IFN-gamma production.The density of Foxp3(+) Tregs in TDLNs was dramatically higher than that in peripheral blood lymphocytes, but significantly lower than that in tumor-infiltrating lymphocytes. Importantly, the frequency of Foxp3(+) Tregs in TDLNs, rather than that in tumors and peripheral blood, was positively correlated with disease stage. In addition, the functions of CD8(+) T cells were impaired in TDLNs compared with peripheral blood lymphocytes and were restored after Treg depletion.Foxp3(+) Tregs in TDLNs are more correlated with disease progression and potentially influence CD8(+) T-cell functions. This study suggests that the frequency of Tregs in TDLNs may provide a valuable prognostic tool in the treatment of CRC.
it takes a(n) (agent-based) village
Authors: teresa satterfield
Journal: Behavioral and Brain Sciences (2005)

steels &amp; belpaeme (s&amp;b) take technical and conceptual shortcuts that have significant negative consequences on simulation implementation and agent behavior. justifiably, their model represents a proof of concept of the role of culturalism in category formation; nevertheless, the absence of detailed information concerning the embodiment of agents and the superficial implementation of learning approaches make their results less relevant than they could be.
Cardiac Index during Intravenous Levarterenol Infusion in Man
Authors: JOHN TUCKMAN, FRANK A. FINNERTY
Journal: Circulation Research (1959)

Cardiac indices were determined by the Stewart-Hamilton indicator-dilution method during intravenous infusions of levarterenol in 25 human subjects. The rate and duration of the infusion as well as the increase in arterial pressure and bradycardia were varied in order to study their influences on the cardiac index.
Risk factors predictive of joint replacement in a 2-year multicentre clinical trial in knee osteoarthritis using MRI: results from over 6 years of observation
Authors: J.-P. Raynauld, J. Martel-Pelletier, B. Haraoui, D. Choquette, M. Dorais, L. M. Wildi, F. Abram, J.-P. Pelletier
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To identify predictive factors for total knee replacement (TKR) using data from MRI of knee osteoarthritis patients in a phase III multicentre disease-modifying osteoarthritis drug (DMOAD) study. <h3>Methods</h3> Knee osteoarthritis patients from a 2-year clinical trial evaluating licofelone versus naproxen were investigated for the incidence of TKR of the study knee. Patients (n=161) who completed the study according to protocol were selected. Incidence of TKR was assessed blindly to the treatment following telephone interviews (n=123). <h3>Results</h3> 18 TKR (14.6%) were performed in 4–7 years following enrolment in the original study. More TKR were performed within the naproxen than the licofelone group (61% vs 39%, p=0.232). Baseline score of bone marrow lesions (BML) in the medial compartment (p=0.0001), medial joint space width (JSW) as assessed by standardised radiographs (p=0.0008), presence of severe medial meniscal tear (p=0.004), medial meniscal extrusion (p=0.013), and C-reactive protein level (p=0.049) were strong predictors of TKR. Changes at the end of the study also yielded strong predictors: change in cartilage volume of the medial compartment (p=0.005) and of the global knee (p=0.034), reduction in the JSW of greater than 7% (p=0.009), and WOMAC pain (p=0.009) and function (p=0.023) scores. Multivariate analysis showed that baseline severe medial meniscal tear (p=0.023) and presence of medial BML (p=0.025) were the strongest independent long-term predictors of TKR. <h3>Conclusion</h3> This study shows that in the context of osteoarthritis trials, clinical data and structural changes identified by MRI allow prediction of a 'hard' outcome such as TKR. The findings support the usefulness and predictive value of MRI in defining study outcome in DMOAD trials.