tbuckley/cabot-search huggingface dataset:
CD44 is of Functional Importance for Colorectal Cancer Stem Cells
Authors: Lei Du, Hongyi Wang, Leya He, Jingyu Zhang, Biyun Ni, Xiaohui Wang, Haijing Jin, Nathalie Cahuzac, Maryam Mehrpour, Youyong Lu, Quan Chen
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Both CD44 and CD133 were reported as putative markers for isolating colorectal cancer stem cells (CSC). It remains to be resolved if both of these markers are of functional importance for colorectal CSC. Experimental Design: The expression of CD44 and CD133 in normal colonic tissues and primary colorectal cancer was assessed by immunohistochemistry in a series of 60 patients on tissue microarray sections. Both in vitro clonogenic and in vivo tumorigenic assay were applied to measure CSC activities from the cells isolated from patients. Lentiviral RNA interference was used to stably knock down CD44 or CD133 in colorectal cancer cells from patients. Results: We found that CD44+ cells displayed clustered growth and they did not colocalize with CD133+ cells within colorectal cancer. As few as 100 CD44+ cells from a patients' tumor initiated a xenograft tumor in vivo. A single CD44+ cell from a tumor could form a sphere in vitro which has characteristic stem cell properties and was able to generate a xenograft tumor resembling the properties of the primary tumor. Knockdown of CD44, but not CD133, strongly prevented clonal formation and inhibited tumorigenicity in xenograft model. Conclusions: These results indicate that CD44 is a robust marker and is of functional importance for colorectal CSC for cancer initiation.
Chronic Phosphocreatine Depletion by the Creatine Analogue β-Guanidinopropionate Is Associated With Increased Mortality and Loss of ATP in Rats After Myocardial Infarction
Authors: Michael Horn, Helga Remkes, Hinrik Strömer, Charlotte Dienesch, Stefan Neubauer
Journal: Circulation (2001)

The failing myocardium is characterized by reductions of phosphocreatine (PCr) and free creatine content and by decreases of energy reserve via creatine kinase (CK), ie, CK reaction velocity (Flux(CK)). It has remained unclear whether these changes contribute directly to contractile dysfunction. In the present study, myocardial PCr stores in a heart failure model were further depleted by feeding of the PCr analogue beta-guanidinopropionate (GP). Functional and metabolic consequences were studied.Rats were subjected to sham operation or left coronary artery ligation (MI). Surviving rats were assigned to 4 groups and fed with 0% (n=7, Sham; n=5, MI) or 1% (n=7 Sham+GP, n=8 MI+GP) GP. Two additional groups were fed GP for 2 or 4 weeks before MI. After 8 weeks, hearts were isolated and perfused, and left ventricular pressure-volume curves were obtained. High-energy phosphate metabolism was determined with (31)P NMR spectroscopy. After GP feeding or MI, left ventricular pressure-volume curves were depressed by 33% and 32%, respectively, but GP feeding in MI hearts did not further impair mechanical function. Both MI and GP feeding reduced PCr content and Flux(CK), but here, effects were additive. In MI+GP rats, PCr levels and Flux(CK) were reduced by 87% and 94%, respectively. Although ATP levels were maintained in the GP and MI groups, ATP content was reduced by 18% in MI+GP hearts. Furthermore, 24-hour mortality in GP-prefed rats was 100%.Rats with an 87% predepletion of myocardial PCr content cannot survive an acute MI. Chronically infarcted hearts subjected to additional PCr depletion cannot maintain ATP homeostasis.
Cd11c+B220+Gr-1+ Cells in Mouse Lymph Nodes and Spleen Display Characteristics of Plasmacytoid Dendritic Cells
Authors: Hideki Nakano, Manabu Yanagita, Michael Dee Gunn
Journal: The Journal of Experimental Medicine (2001)

Human plasmacytoid dendritic cells (pDCs) are major producers of IFNα, are activated by CpG motifs, and are believed to enter lymph nodes (LNs) via L-selectin dependent extravasation across high endothelial venules. To identify a similar murine DC type, CD11c+ cells in the LNs of L-selectin–deficient and control BALB/c mice were compared, revealing a population of CD11c+CD11b− cells that is reduced 85% in the LNs of L-selectin–deficient mice. These cells are Gr-1+B220+CD19−, either CD4+ or CD8+, and localize within T cell zones of LNs. Freshly isolated CD11c+Gr-1+ cells express major histocompatibility complex class II at low levels, display a plasmacytoid morphology, and survive poorly in culture. Their survival is increased and they develop a DC-like morphology in interleukin 3 and CpG. Like human pDCs, CD11c+Gr-1+ cells stimulate T cell proliferation after activation with CpG and produce IFNα after stimulation with influenza virus. These cells also display a strain-specific variation in frequency, being fivefold increased in the LNs of BALB/c relative to C57BL/6 mice. These CD11c+CD11b−B220+Gr-1+ cells appear to be the murine equivalent of human pDCs.
Effect of Anti-inflammatory Treatment on Depression, Depressive Symptoms, and Adverse Effects
Authors: Ole Köhler, Michael E. Benros, Merete Nordentoft, Michael E. Farkouh, Rupa L. Iyengar, Ole Mors, Jesper Krogh
Journal: JAMA Psychiatry (2014)

Several studies have reported antidepressant effects of anti-inflammatory treatment; however, the results have been conflicting and detrimental adverse effects may contraindicate the use of anti-inflammatory agents.To systematically review the antidepressant and possible adverse effects of anti-inflammatory interventions.Trials published prior to December, 31, 2013, were identified searching Cochrane Central Register of Controlled Trials, PubMed, EMBASE, PsychINFO, Clinicaltrials.gov, and relevant review articles.Randomized placebo-controlled trials assessing the efficacy and adverse effects of pharmacologic anti-inflammatory treatment in adults with depressive symptoms, including those who fulfilled the criteria for depression.Data were extracted by 2 independent reviewers. Pooled standard mean difference (SMD) and odds ratios (ORs) were calculated.Depression scores after treatment and adverse effects.Ten publications reporting on 14 trials (6262 participants) were included: 10 trials evaluated the use of nonsteroidal anti-inflammatory drugs (NSAIDs) (n=4,258) and 4 investigated cytokine inhibitors (n=2,004). The pooled effect estimate suggested that anti-inflammatory treatment reduced depressive symptoms (SMD, -0.34; 95% CI, -0.57 to -0.11; I2=90%) compared with placebo. This effect was observed in studies including patients with depression (SMD, -0.54; 95% CI, -1.08 to -0.01; I2=68%) and depressive symptoms (SMD, -0.27; 95% CI, -0.53 to -0.01; I2=68%). The heterogeneity of the studies was not explained by differences in inclusion of clinical depression vs depressive symptoms or use of NSAIDs vs cytokine inhibitors. Subanalyses emphasized the antidepressant properties of the selective cyclooxygenase 2 inhibitor celecoxib (SMD, -0.29; 95% CI, -0.49 to -0.08; I2=73%) on remission (OR, 7.89; 95% CI, 2.94 to 21.17; I2=0%) and response (OR, 6.59; 95% CI, 2.24 to 19.42; I2=0%). Among the 6 studies reporting on adverse effects, we found no evidence of an increased number of gastrointestinal or cardiovascular events after 6 weeks or infections after 12 weeks of anti-inflammatory treatment compared with placebo. All trials were associated with a high risk of bias owing to potentially compromised internal validity.Our analysis suggests that anti-inflammatory treatment, in particular celecoxib, decreases depressive symptoms without increased risks of adverse effects. However, a high risk of bias and high heterogeneity made the mean estimate uncertain. This study supports a proof-of-concept concerning the use of anti-inflammatory treatment in depression. Identification of subgroups that could benefit from such treatment might be warranted.
ONTOGENY OF B LYMPHOCYTES
Authors: Michael C. Gelfand, Gerald J. Elfenbein, Michael M. Frank, William E. Paul
Journal: The Journal of Experimental Medicine (1974)

Many bursa-equivalent (B) lymphocytes of adult mice bear surface Ig and receptors for C3. The frequency of Ig-bearing cells increases rapidly immediately after birth, but these cells lack complement (C) receptors. Lymphocytes bearing C receptors are not found in the spleens of BALB/c, DBA/2, and C57BL/6 mice until 2 wk of age and do not attain substantial numbers until 3–4 wk of age. In AKR mice, a lag between appearance of Ig-bearing and complement receptor lymphocytes (CRL) is also observed but it is of much shorter duration. AKR mice have a frequency of CRL at 2 wk of age of 28% in comparison to a frequency of 4.8% for DBA/2 mice. The difference in frequency between young and adult mice and between "low" and "high CRL" strains cannot be explained by a nonspecific inability to form rosettes as similar results are obtained with soluble antigen-antibody-complement complexes. Analysis of CRL frequency in (AKR x DBA/2)F1 mice and F1 x parental backcross progeny suggests that two independent genes control the rate of appearance of CRL. Furthermore, the genetic difference in the ontogeny of CRL is recapitulated in the repopulation of the B-lymphocyte line in adult-irradiated mice restored with syngeneic bone marrow. Thus, the "CRL genes" described here appear to control B-cell differentiation throughout life.
Massive Spontaneous Renal Cyst Hemorrhage
Authors: C. Dale Brown
Journal: JAMA (1978)

MASSIVE spontaneous renal hemorrhage (bleeding without trauma) is rare. Usually, communication with the renal collecting system exists and gross hematuria is the presenting complaint. On occasion, there is no communication with the collecting system, and blood accumulates as a hematoma in the renal parenchyma (intrarenal hematoma) beneath the renal capsule (subcapsular hematoma), or beyond Gerota's fascia (pararenal hematoma).<sup>1</sup>Demonstration of bleeding during angiography in a nontraumatized kidney has been observed in only a few instances.<sup>2</sup>Demonstration of a bleeding site in the wall of a benign renal cyst and presentation as a pararenal hematoma with massive spontaneous hematuria has not, to our knowledge, been previously reported. <h3>Report of a Case</h3> A 65-year-old man was first seen in the emergency room with uncontrolled, massive renal bleeding. No history of recent or remote kidney trauma could be obtained. Two years before, the patient had had a brief, spontaneous, nonpainful episode
Empirical treatment of influenza-associated pneumonia in primary care: a descriptive study of the antimicrobial susceptibility of lower respiratory tract bacteria (England, Wales and Northern Ireland, January 2007-March 2010)
Authors: R. M. Blackburn, K. L. Henderson, M. Lillie, E. Sheridan, R. C. George, A. H. B. Deas, A. P. Johnson
Journal: Thorax (2011)

To determine the susceptibility of lower respiratory tract (LRT) isolates of Streptococcus pneumoniae, Staphylococcus aureus and Haemophilus influenzae to antimicrobial agents recommended by UK guidelines for treatment of pneumonia associated with influenza-like illness.Analysis of antimicrobial susceptibility data from sentinel microbiology laboratories in England, Wales and Northern Ireland was carried out. Subjects comprised patients who had an LRT specimen taken in a general practitioner surgery or hospital outpatient setting between January 2007 and March 2010. The main outcome measurements were antimicrobial susceptibility trends of LRT isolates over time, between patient age groups and in different geographical regions.Susceptibility to tetracyclines or co-amoxiclav was high. Of the 70,288 and 45,288 isolates with susceptibility results for tetracyclines or co-amoxiclav, 96% and 92%, respectively, were susceptible. Overall susceptibility to ciprofloxacin, ampicillin/amoxicillin and macrolides was lower than for tetracyclines or co-amoxiclav and varied markedly by organism. There were few clinically relevant variations in susceptibility to doxycycline or co-amoxiclav over time, geographically or between age groups.The data support the use of doxycycline or co-amoxiclav as appropriate empiric treatment for LRT infection caused by the pathogens investigated, for patients in primary care.
Omalizumab in patients with symptomatic chronic idiopathic/spontaneous urticaria despite standard combination therapy
Authors: Allen Kaplan, Dennis Ledford, Mark Ashby, Janice Canvin, James L. Zazzali, Edward Conner, Joachim Veith, Nikhil Kamath, Petra Staubach, Thilo Jakob, Robert G. Stirling, Piotr Kuna, William Berger, Marcus Maurer, Karin Rosén
Journal: Journal of Allergy and Clinical Immunology (2013)
Constitutive versus Activation-dependent Cross-Presentation of Immune Complexes by CD8+ and CD8− Dendritic Cells In Vivo
Authors: Joke M.M. den Haan, Michael J. Bevan
Journal: The Journal of Experimental Medicine (2002)

Murine splenic dendritic cells (DCs) can be divided into two subsets based on CD8α expression, but the specific role of each subset in stimulation of T cells is largely unknown. An important function of DCs is the ability to take up exogenous antigens and cross-present them in the context of major histocompatibility complex (MHC) class I molecules to CD8+ T cells. We previously demonstrated that, when cell-associated ovalbumin (OVA) is injected into mice, only the CD8+ DC subset cross-presents OVA in the context of MHC class I. In contrast to this selectivity with cell-associated antigen, we show here that both DC subsets isolated from mice injected with OVA/anti-OVA immune complexes (OVA-IC) cross-present OVA to CD8+ T cells. The use of immunoglobulin G Fc receptor (FcγR) common γ-chain–deficient mice revealed that the cross-presentation by CD8− DCs depended on the expression of γ-chain–containing activating FcγRs, whereas cross-presentation by CD8+ DCs was not reduced in γ-chain–deficient mice. These results suggest that although CD8+ DCs constitutively cross-present exogenous antigens in the context of MHC class I molecules, CD8− DCs only do so after activation, such as via ligation of FcγRs. Cross-presentation of immune complexes may play an important role in autoimmune diseases and the therapeutic effect of antitumor antibodies.
Stimulation of rat hepatic low density lipoprotein receptors by glucagon. Evidence of a novel regulatory mechanism in vivo.
Authors: M Rudling, B Angelin
Journal: Journal of Clinical Investigation (1993)

We studied the influence of glucagon on hepatic LDL receptors and plasma lipoproteins in rats. A dose-dependent (maximum, threefold) increase in LDL-receptor binding was evident already at a dose of 2 x 4 micrograms, and detectable 3 h after injection; concomitantly, cholesterol and apolipoprotein (apo) B and apoE within LDL and large HDL decreased in plasma. LDL receptor mRNA levels were however unaltered or reduced. Hepatic microsomal cholesterol was increased and the enzymatic activities of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol 7 alpha-hydroxylase in hepatic microsomes were reduced. Insulin alone increased receptor binding and receptor mRNA levels twofold, but plasma cholesterol was unchanged and plasma apoE and apoB increased. Administration of insulin to glucagon-treated animals reduced the LDL-receptor binding to control levels and apoB appeared in LDL particles. Estrogen treatment increased LDL-receptor binding and mRNA levels five- and eightfold, respectively. Combined treatment with glucagon and estrogen reduced the stimulation of LDL-receptor mRNA levels by 80% although LDL-receptor binding was unchanged. Immunoblot analysis showed that glucagon increased the number of hepatic LDL receptors. We conclude that glucagon induces the number of hepatic LDL receptors by a mechanism not related to increased mRNA levels, suggesting the presence of a posttranscriptional regulatory mechanism present in the liver in vivo.
Choline Kinase Is a Novel Oncogene that Potentiates RhoA-Induced Carcinogenesis
Authors: Ana Ramírez de Molina, David Gallego-Ortega, Jacinto Sarmentero, Mónica Bañez-Coronel, Yolanda Martín-Cantalejo, Juan Carlos Lacal
Journal: Cancer Research (2005)

Abstract Choline kinase is overexpressed in human breast, lung, colorectal, and prostate tumors, a finding that suggests the involvement of this enzyme in carcinogenesis. Here we show that overexpression of choline kinase induce oncogenic transformation of human embryo kidney fibroblasts and canine epithelial Madin-Darby canine kidney cells. Choline kinase lays downstream of RhoA signaling and is activated through ROCK kinase, one of the best-characterized RhoA effectors. In keeping with this, coexpression of RhoA and choline kinase potentiates both anchorage independent growth and tumorigenesis. Finally, choline kinase–mediated transformation is sensitive to MN58b, a well-characterized specific choline kinase inhibitor. These results provide the definitive evidence that choline kinase has oncogenic properties and that choline kinase inhibition constitutes a novel valid antitumor strategy.
Quantitative Studies of Triglyceride Lipolysis after Heparin Administration
Authors: HYMAN ENGELBERG
Journal: Circulation Research (1958)

The extent of triglyceride lipolysis by postheparin lipemia clearing factor (lipoprotein lipase) was studied in vitro in 8 atherosclerotic individuals. Varying doses of heparin were injected intravenously and subcutaneously and blood was drawn at stated time intervals for analysis. The rate of splitting of human low density lipoproteins was then determined by measurement of the rate of release of unesterified fatty acids upon incubation of postheparin plasma plus lipoproteins in vitro at 37 C. The data obtained gives a range of the minimum in vivo removal of alimentary neutral fat following an injection of heparin.
Surgical reconstruction of regurgitant common atrioventricular valve to create double valvular orifices
Authors: Takuya Miura, Hidefumi Kishimoto, Hiroaki Kawata, Masatoshi Hata, Takaya Hoashi, Tohru Nakajima, Futoshi Kayatani, Noboru Inamura, Tsubura Ishii, Yukiko Kado
Journal: Journal of the American College of Cardiology (2003)
Developing ovarian cancer stem cell models: laying the pipeline from discovery to clinical intervention
Authors: Brendan Ffrench, Claudia Gasch, John J O’Leary, Michael F Gallagher
Journal: Molecular Cancer (2014)

Despite decades of research, ovarian cancer is still associated with unacceptably high mortality rates, which must be addressed by novel therapeutic approaches. One avenue through which this may be achieved is targeting of tumor-initiating 'Cancer Stem Cells' (CSCs). CSCs are sufficient to generate primary and recurrent disease through extensive rounds of asymmetric division, which maintain the CSC pool while producing the tissues that form the bulk of the tumor. CSCs thrive in the harsh tumor niche, are generally refractory to therapeutic intervention and closely-linked to the Epithelial-Mesenchymal Transition process, which facilitates invasion and metastasis. While it is well-accepted that CSC-targeting must be assessed as a novel therapeutic avenue, few ovarian CSC models have been developed due to perceived and actual difficulties associated with the process of 'CSC Discovery'. In this article we review contemporary approaches to CSC Discovery and argue that this process should start with an understanding of the specific challenges associated with clinical intervention, laying the pipeline backwards towards CSC Discovery. Such an approach would expedite the bridging of the gap between laboratory isolation and clinical targeting of ovarian CSCs.
Measurement of children's exposure to pesticides: analysis of urinary metabolite levels in a probability-based sample.
Authors: J L Adgate, D B Barr, C A Clayton, L E Eberly, N C Freeman, P J Lioy, L L Needham, E D Pellizzari, J J Quackenboss, A Roy, K Sexton
Journal: Environmental Health Perspectives (2001)

The Minnesota Children's Pesticide Exposure Study is a probability-based sample of 102 children 3-13 years old who were monitored for commonly used pesticides. During the summer of 1997, first-morning-void urine samples (1-3 per child) were obtained for 88% of study children and analyzed for metabolites of insecticides and herbicides: carbamates and related compounds (1-NAP), atrazine (AM), malathion (MDA), and chlorpyrifos and related compounds (TCPy). TCPy was present in 93% of the samples, whereas 1-NAP, MDA, and AM were detected in 45%, 37%, and 2% of samples, respectively. Measured intrachild means ranged from 1.4 microg/L for MDA to 9.2 microg/L for TCPy, and there was considerable intrachild variability. For children providing three urine samples, geometric mean TCPy levels were greater than the detection limit in 98% of the samples, and nearly half the children had geometric mean 1-NAP and MDA levels greater than the detection limit. Interchild variability was significantly greater than intrachild variability for 1-NAP (p = 0.0037) and TCPy (p < 0.0001). The four metabolites measured were not correlated within urine samples, and children's metabolite levels did not vary systematically by sex, age, race, household income, or putative household pesticide use. On a log scale, mean TCPy levels were significantly higher in urban than in nonurban children (7.2 vs. 4.7 microg/L; p = 0.036). Weighted population mean concentrations were 3.9 [standard error (SE) = 0.7; 95% confidence interval (CI), 2.5, 5.3] microg/L for 1-NAP, 1.7 (SE = 0.3; 95% CI, 1.1, 2.3) microg/L for MDA, and 9.6 (SE = 0.9; 95% CI, 7.8, 11) microg/L for TCPy. The weighted population results estimate the overall mean and variability of metabolite levels for more than 84,000 children in the census tracts sampled. Levels of 1-NAP were lower than reported adult reference range concentrations, whereas TCPy concentrations were substantially higher. Concentrations of MDA were detected more frequently and found at higher levels in children than in a recent nonprobability-based sample of adults. Overall, Minnesota children's TCPy and MDA levels were higher than in recent population-based studies of adults in the United States, but the relative magnitude of intraindividual variability was similar for adults and children.
Identification of Distinct Luminal Domains for Macromolecules, Erythrocytes, and Leukocytes Within Mammalian Capillaries
Authors: Hans Vink, Brian R. Duling
Journal: Circulation Research (1996)

A thick endothelial surface coat consisting of the glycocalyx and associated plasma proteins has been hypothesized to reduce functional capillary volume available for flowing plasma macromolecules and blood cells. The purpose of this study was to compare anatomic and functional capillary diameters available for macromolecules, RBCs, and WBCs in hamster cremaster muscle capillaries. Bright-field and fluorescence microscopy provided similar estimates (mean±SE) of the anatomic capillary diameter: 5.1±0.1 μm (bright field, 39 capillaries in 10 animals) and 5.1±0.2 μm (membrane dye PKH26, 18 capillaries in 2 animals). Estimates of functional diameters were obtained by measuring the width of RBCs and WBCs and the intracapillary distribution of systemically injected fluorescein isothiocyanate (FITC)–dextran 70. WBCs (5.1±0.2 μm) fully occupied the anatomic capillary cross section. In contrast, the widths of RBCs (3.9±0.2 μm, 21 capillaries in 8 animals) and FITC-dextran (4.3±0.2 μm, 21 capillaries in 8 animals) were significantly smaller than the anatomic capillary diameter. Continuous (1- to 5-minute) excitation of fluorochromes in the capillary lumen (light-dye treatment) increased the width of RBCs passing the treated site from 3.6±0.3 to 4.4±0.3 μm (6 capillaries in 4 animals) and the width of the FITC-dextran column from 4.1±0.2 to 4.6±0.3 μm (10 capillaries in 7 animals). Furthermore, light-dye treatment increased capillary tube hematocrit by 60% in 40-μm-long capillary segments compared with untreated sites in the same capillaries. It is concluded that the wall of skeletal muscle capillaries is decorated with a 0.4- to 0.5-μm-thick endothelial surface coat, which may represent the true active interface between blood and the capillary wall.