tbuckley/cabot-search huggingface dataset:
CNI-1493 inhibits Aβ production, plaque formation, and cognitive deterioration in an animal model of Alzheimer's disease
Authors: Michael Bacher, Richard Dodel, Bayan Aljabari, Kathy Keyvani, Philippe Marambaud, Rakez Kayed, Charles Glabe, Nicole Goertz, Anne Hoppmann, Norbert Sachser, Jens Klotsche, Susanne Schnell, Lars Lewejohann, Yousef Al-Abed
Journal: The Journal of Experimental Medicine (2008)

Alzheimer's disease (AD) is characterized by neuronal atrophy caused by soluble amyloid beta protein (Abeta) peptide "oligomers" and a microglial-mediated inflammatory response elicited by extensive amyloid deposition in the brain. We show that CNI-1493, a tetravalent guanylhydrazone with established antiinflammatory properties, interferes with Abeta assembly and protects neuronal cells from the toxic effect of soluble Abeta oligomers. Administration of CNI-1493 to TgCRND8 mice overexpressing human amyloid precursor protein (APP) for a treatment period of 8 wk significantly reduced Abeta deposition. CNI-1493 treatment resulted in 70% reduction of amyloid plaque area in the cortex and 87% reduction in the hippocampus of these animals. Administration of CNI-1493 significantly improved memory performance in a cognition task compared with vehicle-treated mice. In vitro analysis of CNI-1493 on APP processing in an APP-overexpressing cell line revealed a significant dose-dependent decrease of total Abeta accumulation. This study indicates that the antiinflammatory agent CNI-1493 can ameliorate the pathophysiology and cognitive defects in a murine model of AD.
Microarray-Based Class Discovery for Molecular Classification of Breast Cancer: Analysis of Interobserver Agreement
Authors: Alan Mackay, Britta Weigelt, Anita Grigoriadis, Bas Kreike, Rachael Natrajan, Roger A’Hern, David S.P. Tan, Mitch Dowsett, Alan Ashworth, Jorge S. Reis-Filho
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundBreast cancers can be classified by hierarchical clustering using an "intrinsic" gene list into one of at least five molecular subtypes: basal-like, HER2, luminal A, luminal B, and normal breast-like. Five different intrinsic gene lists composed of varying numbers of genes have been used for molecular subtype identification and classification of breast cancers. The aim of this study was to determine the objectivity and interobserver reproducibility of the assignment of molecular subtype classes by hierarchical cluster analysis.
Programmed death-1 (PD-1) defines a transient and dysfunctional oligoclonal T cell population in acute homeostatic proliferation
Authors: Sue-Jane Lin, Craig D. Peacock, Kapil Bahl, Raymond M. Welsh
Journal: The Journal of Experimental Medicine (2007)

The host responds to lymphopenic environments by acute homeostatic proliferation, which is a cytokine- and endogenous peptide-driven expansion of lymphocytes that restores the numbers and diversity of T cells. It is unknown how these homeostatically proliferating (HP) cells are ultimately controlled. Using a system where lymphocytic choriomeningitis virus-immune C57BL/6 splenocytes were transferred into lymphopenic T cell-deficient hosts and allowed to reconstitute the environment, we defined the following three populations of T cells: slowly dividing Ly6C+ cells, which contained bona fide virus-specific memory cells, and more rapidly dividing Ly6C- cells segregating into programmed death (PD)-1+ and PD-1- fractions. The PD-1+ HP cell population, which peaked in frequency at day 21, was dysfunctional in that it failed to produce interferon gamma or tumor necrosis factor alpha on T cell receptor (TCR) stimulation, had down-regulated expression of interleukin (IL)-7Ralpha, IL-15Rbeta, and Bcl-2, and reacted with Annexin V, which is indicative of a preapoptotic state. The PD-1+ HP cells, in contrast to other HP cell fractions, displayed highly skewed TCR repertoires, which is indicative of oligoclonal expansion; these skewed repertoires and the PD-1+ population disappeared by day 70 from the host, presumably because of apoptosis. These results suggest that PD-1 may play a negative regulatory role to control rapidly proliferating and potentially pathogenic autoreactive CD8+ T cells during homeostatic reconstitution of lymphopenic environments.
Influence of the Vitreomacular Interface on Treatment Outcomes in the Comparison of Age-Related Macular Degeneration Treatments Trials
Authors: Thomas A. Cuilla, Gui-shuang Ying, Maureen G. Maguire, Daniel F. Martin, Glenn J. Jaffe, Juan E. Grunwald, Ebenezer Daniel, Cynthia A. Toth
Journal: Ophthalmology (2015)
Targeted Replacement of Kv1.5 in the Mouse Leads to Loss of the 4-Aminopyridine–Sensitive Component of <i>I</i> <sub>K,slow</sub> and Resistance to Drug-Induced QT Prolongation
Authors: Barry London, Weinong Guo, Xiang-hua Pan, Joon S. Lee, Vladimir Shusterman, Christopher J. Rocco, Diomedes A. Logothetis, Jeanne M. Nerbonne, Joseph A. Hill
Journal: Circulation Research (2001)

Abstract —The K + channel mKv1.5 is thought to encode a 4-aminopyridine (4-AP)–sensitive component of the current I K,slow in the mouse heart. We used gene targeting to replace mKv1.5 with the 4-AP–insensitive channel rKv1.1 (SWAP mice) and directly test the role of Kv1.5 in the mouse ventricle. Kv1.5 RNA and protein were undetectable, rKv1.1 was expressed, and Kv2.1 protein was upregulated in homozygous SWAP hearts. The density of the K + current I K,slow (depolarizations to +40 mV, pA/pF) was similar in left ventricular myocytes isolated from SWAP homozygotes (17±1, n=27) and littermate controls (16±2, n=19). The densities and properties of I peak , I to,f , I to,s , and I ss were also unchanged. In homozygous SWAP myocytes, the 50-μmol/L 4-AP–sensitive component of IK,slow was absent (n=6), the density of the 20-mmol/L tetraethylammonium-sensitive component of I K,slow was increased (9±1 versus 5±1, P &lt;0.05), and no 100- to 200-nmol/L α-dendrotoxin–sensitive current was found (n=8). APD 90 in SWAP myocytes was similar to controls at baseline but did not prolong in response to 30 μmol/L 4-AP. Similarly, QTc (ms) was not prolonged in anesthetized SWAP mice (64±2, homozygotes, n=9; 62±2, controls, n=9), and injection with 4-AP prolonged QTc only in controls (63±1, homozygotes; 72±2, controls; P &lt;0.05). SWAP mice had no increase in arrhythmias during ambulatory telemetry monitoring. Thus, Kv1.5 encodes the 4-AP–sensitive component of I K,slow in the mouse ventricle and confers sensitivity to 4-AP–induced prolongation of APD and QTc. Compensatory upregulation of Kv2.1 may explain the phenotypic differences between SWAP mice and the previously described transgenic mice expressing a truncated dominant-negative Kv1.1 construct.
Prognostic potential of 1,3-beta-d-glucan levels in bronchoalveolar lavage fluid samples
Authors: Frederike M.J. Reischies, Juergen Prattes, Florian Prüller, Susanne Eigl, Agnes List, Albert Wölfler, Walter Buzina, Ines Zollner-Schwetz, Thomas Valentin, Jasmin Rabensteiner, Holger Flick, Robert Krause, Reinhard B. Raggam, Martin Hoenigl
Journal: Journal of Infection (2015)
Murine Natural Killer Cells and Marrow Graft Rejection
Authors: Y. Y. L. Yu, V. Kumar, M. Bennett
Journal: Annual Review of Immunology (1992)

Rejection of bone marrow transplants in lethally irradiated mice differs from rejection of solid tissue grafts in several respects. The genetic laws that govern rejection of solid tissue grafts often fail with hemopoietic grafts. For example, F1 hybrids between two H-2 disparate strains of mice often reject parental bone marrow cells (BMC), and conversely, marrow cells of F1 hybrids (H-2 heterozygous) are usually not rejected by either parent or an unrelated allogeneic recipient. Thus, unlike the classical MHC antigens, the hemopoietic histocompatibility (Hh) antigens relevant marrow graft rejection are inherited in a recessive pattern. The major Hh (Hh-1) locus maps within the mouse H-2 complex between the H-2S and H-2D regions, and it can therefore be dissociated from the class-I MHC genes. Nevertheless, it is possible that class-I MHC antigens play a role in the formation or expression of Hh-1 antigens. Three models that explain the possible relationship between class-I MHC and Hh-1 genes and the noncodominant pattern of inheritance of Hh antigens are presented. The effector cells responsible for resisting BMC grafts are different from those responsible for rejection of solid tissue grafts. Three cell types, natural killer cells (CD3 - , NK1.1 + ), cytotoxic T cells (CD3 + , CD8 + ), and T cells with natural killer cell markers (CD3 + , NK1.1 + ) have been implicated in the rejection of BMC grafts. Involvement of these cell types is reviewed and the relative roles played by each are discussed. Evidence supporting the existence of Hh-1 specific subsets of NK cells is presented.
Autophagy in cardiac myocyte homeostasis, aging, and pathology
Authors: A TERMAN, U BRUNK
Journal: Cardiovascular Research (2005)

Autophagy, an intralysosomal degradation of cells' own constituents that includes macro-, micro-, and chaperone-mediated autophagy, plays an important role in the renewal of cardiac myocytes. This cell type is represented by long-lived postmitotic cells with very poor (if any) replacement through differentiation of stem cells. Macroautophagy, the most universal form of autophagy, is responsible for the degradation of various macromolecules and organelles including mitochondria and is activated in response to stress, promoting cell survival. This process is also involved in programmed cell death when injury is irreversible. Even under normal conditions, autophagy is somewhat imperfect, underlying gradual accumulation of defective mitochondria and lipofuscin granules within aging cardiac myocytes. Autophagy is involved in the most important cardiac pathologies including myocardial hypertrophy, cardiomyopathies, and ischemic heart disease, a fact that has led to increasing attention to this process.
Variations in Mortality among Hospitalizations for Acute Kidney Injury
Authors: William M. McClellan
Journal: Journal of the American Society of Nephrology (2010)

Health insurance, setting of care, geography, and primary disease all affect mortality among various populations in the United States.1,2 If medical care for these different populations were truly comparable, then we might expect similar mortality outcomes and attribute differences to random variation. Unfortunately, population-to-population variations in mortality are frequently observed and persist even after controlling for individual patient characteristics. This suggests potentially remediable differences in the content, organization, and delivery of health care may be important in shaping true variation.3–6 Such modifiable differences in health care–related mortality, if they exist, warrant special attention as clinical and public health problems.

This conceptual framework should be familiar to nephrologists. The national ESRD surveillance system, comprising the ESRD Networks and the US Renal Data System, consistently reports the likelihood of receiving a kidney transplant, mortality in hemodialysis patients, or incident ESRD differ in a nonrandom manner among patient groups, among geographic areas, and over time.7 Variations in patient care associated with these outcomes are reported as well,8 and interventions during the past 15 years to reduce variations in providing hemodialysis have substantially reduced mortality among patients with ESRD.9–11

An important question is the extent to which this conceptual framework extends to other aspects of clinical nephrology. One area in which new ideas are being piloted is in pre-ESRD care for stage 4 chronic kidney disease (CKD). The Centers for Medicare and Medicaid Services recently piloted surveillance and quality improvement activities to test the applicability of reducing variations in care in earlier stages of CKD among primary care physicians.12 If surveillance data can be used to direct targeted interventions to improve the care of patients with earlier stages of CKD, then nephrologists may be able to translate evidence-based clinical practice …
Proline Oxidase Functions as a Mitochondrial Tumor Suppressor in Human Cancers
Authors: Yongmin Liu, Gregory L. Borchert, Steven P. Donald, Bhalchandra A. Diwan, Miriam Anver, James M. Phang
Journal: Cancer Research (2009)

Tumor metabolism and bioenergetics have become important topics for cancer research and are promising targets for anticancer therapy. Although glucose serves as the main source of energy, proline, an alternative substrate, is important, especially during nutrient stress. Proline oxidase (POX), catalyzing the first step in proline catabolism, is induced by p53 and can regulate cell survival as well as mediate programmed cell death. In a mouse xenograft tumor model, we found that POX greatly reduced tumor formation by causing G2 cell cycle arrest. Furthermore, immunohistochemical staining showed decreased POX expression in tumor tissues. Importantly, HIF-1alpha signaling was impaired with POX expression due to the increased production of alpha-ketoglutarate, a critical substrate for prolyl hydroxylation and degradation of HIF-1alpha. Combined with previous in vitro findings and reported clinical genetic associations, these new findings lead us to propose POX as a mitochondrial tumor suppressor and a potential target for cancer therapy.
Weber-Christian panniculitis.
Authors: S P Conway, R W Smithells, W M Peters
Journal: Annals of the Rheumatic Diseases (1987)

Two cases of Weber-Christian panniculitis with onset at 7 months and 3 years 6 months are described. Both show evidence of disturbances in immune mechanisms. The family of the first case has a high prevalence of coeliac disease, and the mother of the first patient also suffers from alopecia areata and dermatitis herpetiformis.
Female gender: risk factor for congenital long QT-related arrhythmias
Authors: C. Valenzuela
Journal: Cardiovascular Research (2012)

This editorial refers to ‘Increased late sodium current contributes to long QT-related arrhythmia susceptibility in female mice’ by J.S. Lowe et al ., doi:10.1093/cvr/cvs160. 

Congenital long-QT syndrome (LQTS) is a genetic cardiac channelopathy in which patients exhibit delayed ventricular repolarization that appears as a prolongation of the corrected QT (QTc) interval on the electrocardiogram.1 More than 200 mutations have been found in 13 different genes encoding ion channels, accessory beta subunits, and regulatory proteins.2 Most cases of congenital LQTS are the consequence of the dominant inheritance of a given mutation.2 Kv11.1 mutations are the most frequent ones (45%), followed by those found in Kv7.1 (42%), Nav1.5 (8%), KCNE1 (3%), and KCNE2 (2%).3 In addition, another type of LQTS, the ‘acquired’ LQTS, has been described, mostly as the consequence of drugs able to prolong the cardiac action potential duration.4,5 This lengthening of the cardiac action potential can produce the development of early afterdepolarizations (EADs) and the genesis of a ventricular polymorphic arrhythmia called torsades de pointes …
Non-steroidal anti-inflammatory drugs and ethanol.
Authors: A. M. Porter
Journal: British Journal of Sports Medicine (1982)

Training Champion" phenomenon, "the guy who does it all in training but cannot race" -and on relaxation techniques, particularly the autogenic training so popular in Europe.Finally the World Congress is, of course, the major four-yearly reunion of the International Federation of Sports Medicine and its major business meetings are important focal points for policy developments.The Inter-Federal Medical Commission, which co-ordinates FIMS with the international governing bodies of sport formally called for wider educa- tional programmes in sports medicine, more co-ordination between authorities, particularly to standardise and to improve dope control protocol and for a more prominent voice for the medical viewpoint in sport, particularly in the drafting of safety regulations.
Dynamin 2–dependent endocytosis is required for normal megakaryocyte development in mice
Authors: Markus Bender, Silvia Giannini, Renata Grozovsky, Terese Jönsson, Hilary Christensen, Fred G. Pluthero, Amy Ko, Ann Mullally, Walter H. A. Kahr, Karin M. Hoffmeister, Hervé Falet
Journal: Blood (2014)
Regulation of Angiogenesis by Id-1 through Hypoxia-Inducible Factor-1α–Mediated Vascular Endothelial Growth Factor Up-regulation in Hepatocellular Carcinoma
Authors: Terence K. Lee, Ronnie T.P. Poon, Anthony P. Yuen, Ming Tat Ling, Xiang Hong Wang, Yong Chuan Wong, Xin Yuan Guan, Kwan Man, Zao You Tang, Sheung Tat Fan
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Metastasis is commonly associated with poor prognosis of hepatocellular carcinoma (HCC). Being an important angiogenic factor, vascular endothelial growth factor (VEGF) plays a central role in HCC growth and metastasis. Recently, Id-1 (inhibitor of differentiation/DNA synthesis) has been suggested to be a key factor in cancer progression but the molecular mechanism remains unknown. Experimental Design: We first showed that overexpression of Id-1 was correlated with HCC metastasis (P &amp;lt; 0.001) and its expression was significantly correlated with VEGF expression by tissue microarray. By ectopic transfection of Id-1 into HCC cells, Id-1 was able to induce VEGF secretion through activation of VEGF transcription. Results: Increased VEGF secretion in Id-1 transfectants induced morphologic change and proliferation of human umbilical vascular endothelial cell resulting in promotion of angiogenesis. Id-1 induced transcriptional activation of VEGF by stabilizing hypoxia-inducible factor-1α protein. Down-regulation of Id-1 by antisense approach led to suppression of hypoxia-inducible factor-1α–mediated VEGF production. In addition, Id-1 suppression resulted in retardation of cell invasion through down-regulation of VEGF. Conclusions: Id-1 is a novel angiogenic factor for HCC metastasis and down-regulation of Id-1 may be a novel target to inhibit HCC metastasis through suppression of angiogenesis.
Delays in publication of cost utility analyses conducted alongside clinical trials: registry analysis
Authors: Dan Greenberg, Allison B Rosen, Natalia V Olchanski, Patricia W Stone, John Nadai, Peter J Neumann
Journal: BMJ (2004)

<h3>Abstract</h3> <h3>Introduction</h3> Orthostatic hypotension (OH) is a common cause of hospitalization, particularly in the elderly. Hospitalized patients with OH are often severely ill, with complex medical comorbidities and high rates of disability. Droxidopa is a norepinephrine precursor approved for the treatment of neurogenic OH (nOH) associated with autonomic failure that is commonly used in the outpatient setting, but there is currently no data regarding the safety and efficacy of droxidopa initiation in medically complex patients. <h3>Methods</h3> We performed a retrospective review of patients started on droxidopa for refractory nOH while hospitalized at Vanderbilt University Medical Center between October 2014 and May 2017. Primary outcome measures were safety, change in physician global impression of illness severity from admission to discharge, and persistence on medication after 180-day follow-up. <h3>Results</h3> A total of 20 patients were identified through chart review. Patients were medically complex with high rates of cardiovascular comorbidities and a diverse array of underlying autonomic diagnoses. Rapid titration of droxidopa was safe and well-tolerated in this cohort, with no cardiovascular events or new onset arrhythmias. Supine hypertension requiring treatment occurred in four patients. One death occurred during hospital admission due to organ failure associated with end-stage amyloidosis. Treating physicians noted improvements in presyncopal symptoms in 80% of patients. After 6 months, 13 patients (65%) continued on droxidopa therapy. <h3>Conclusion</h3> In a retrospective cohort of hospitalized, severely ill patients with refractory nOH, supervised rapid titration of droxidopa was safe and effective. Treatment persistence was high, suggesting that symptomatic benefit extended beyond acute intervention.
DIAGNOSIS OF PSITTACOSIS IN MAN BY MEANS OF INJECTIONS OF SPUTUM INTO WHITE MICE
Authors: Thomas M. Rivers, G. P. Berry
Journal: The Journal of Experimental Medicine (1935)

By means of intraperitoneal injections in mice of unfiltered sputum or filtrates of sputum a large percentage of the cases of psittacosis in human beings can be successfully diagnosed in a relatively safe manner.
Breast Neoplasms in Women Treated With X Rays for Acute Postpartum Mastitis. A Pilot Study&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Fred A. Mettler, Jr., Louis H. Hempelmann, M.D., Arthur M. Dutton, Ph.D., James W. Pifer, M.A., Edward T. Toyooka, M.D., Wendell R. Ames, M.D.
Journal: JNCI Journal of the National Cancer Institute (1969)

The incidence of benign and malignant breast tumors in 606 women treated with X rays for acute postpartum mastitis was determined by mail survey. The total cumulative X-ray doses per breast ranged from 75 R (air) to more than 1000 R. The follow-up period in most cases was from 10–25 years. Thirteen confirmed cases of breast cancer were observed instead of the 5.86 cases expected in a comparable group of women in the general population of upstate New York. In 5 of the 13 women with cancer, only one breast was treated; in each case, the cancer arose in the irradiated breast. Twenty-five surgically removed benign breast tumors were reported rather than the four to five cases expected. The incidence of benign tumors appeared to have increased in the untreated as well as in the treated breasts. There was no good evidence of a correlation between the dose and the incidence of malignant and benign tumors. Although a strong association is established between excess breast neoplasms and prior X-ray treatments for mastitis, lack of adequate control studies means that the radiation exposure per se cannot be implicated with certainty as an etiologic factor in the neoplastic transformation. Because irradiation is known to induce breast neoplasms in several species of animals and because of reports of excess breast neoplasms in women after exposure to ionizing radiation, it seems likely that the X-ray treatments were factors in the development of the excess breast tumors. We conclude therefore that at least some breast cancers in this series of women could have been induced by the prior X-ray exposures.