tbuckley/cabot-search huggingface dataset:
STUDIES ON THE BACTERIOPHAGE OF D'HÉRELLE
Authors: Ralph S. Muckenfuss, Charles Korb
Journal: The Journal of Experimental Medicine (1928)

1. The production of exotoxin and of endotoxin by normal Shiga dysentery bacilli and by strains resistant to Laudman phage was found to be the same. 2. The presence of phage did not alter toxin production by the resistant organism.
(R)Evolutionary Therapy: The Potential of Immunotherapy to Fulfill the Promise of Personalized Cancer Treatment
Authors: R. A. Madan, J. L. Gulley
Journal: JNCI Journal of the National Cancer Institute (2014)

Since the millennium, personalized medicine has been at the forefront of therapeutic endeavors in medical oncology. The latest technology has given researchers the ability to define cancer at its molecular core. This has led to the development of "targeted therapies," designed to eliminate driver mutations while leaving healthy cells unscathed. Unfortunately, more than 10 years into the targeted molecular therapy era, successes have been infrequent, and toxicity remains largely unchanged compared with relatively indiscriminant, traditional chemotherapy. Emerging data suggests that the malignant clonal heterogeneity within solid tumors is so diverse that targeting one or even several mutations is likely to have minimal, transient impact. In recent years, new therapies have emerged that can effectively stimulate the immune system and improve survival in patients with metastatic disease. Through immune activation, there is the potential to target the cancer with a biologic diversity that can potentially rival the multiplicity of malignant mutations within tumors. Stimulating the immune system to become an evolving adversary against malignant cells may revolutionize cancer therapy in the years to come.
A new gene coding for a differentiation antigen recognized by autologous cytolytic T lymphocytes on HLA-A2 melanomas.
Authors: P G Coulie, V Brichard, A Van Pel, T Wölfel, J Schneider, C Traversari, S Mattei, E De Plaen, C Lurquin, J P Szikora, J C Renauld, T Boon
Journal: The Journal of Experimental Medicine (1994)

It has been reported previously that antitumor cytolytic T lymphocyte (CTL) clones can be isolated from blood lymphocytes of HLA-A2 melanoma patients, after stimulation in vitro with autologous tumor cells, and that some of these CTL clones lyse most HLA-A2 melanomas. A first antigen recognized by such CTL clones was previously shown to be encoded by the tyrosinase gene. We report here the identification of another gene that also directs the expression of an antigen recognized on most melanomas by CTL clones that are restricted by HLA-A2. The gene, designated Melan-A, is unrelated to any known gene. It is 18 kb long and comprises five exons. Like the tyrosinase gene, it is expressed in most melanoma tumor samples and, among normal cells, only in melanocytes.
Speed/accuracy trade-offs in target-directed movements
Authors: Réjean Plamondon, Adel M. Alimi
Journal: Behavioral and Brain Sciences (1997)

This target article presents a critical survey of the scientific literature dealing with the speed/accuracy trade-offs in rapid-aimed movements. It highlights the numerous mathematical and theoretical interpretations that have been proposed in recent decades. Although the variety of points of view reflects the richness of the field and the high degree of interest that such basic phenomena attract in the understanding of human movements, it calls into question the ability of many models to explain the basic observations consistently reported in the field. This target article summarizes the kinematic theory of rapid human movements, proposed recently by R. Plamondon (1993b; 1993c; 1995a; 1995b), and analyzes its predictions in the context of speed/accuracy trade-offs. Data from human movement literature are reanalyzed and reinterpreted in the context of the new theory. It is shown that the various aspects of speed/ accuracy trade-offs can be taken into account by considering the asymptotic behavior of a large number of coupled linear systems, from which a delta-lognormal law can be derived to describe the velocity profile of an end-effector driven by a neuromuscular synergy. This law not only describes velocity profiles almost perfectly, it also predicts the kinematic properties of simple rapid movements and provides a consistent framework for the analysis of different types of speed/accuracy trade-offs using a quadratic (or power) law that emerges from the model.
Targeting Cancer Stem Cells through L1CAM Suppresses Glioma Growth
Authors: Shideng Bao, Qiulian Wu, Zhizhong Li, Sith Sathornsumetee, Hui Wang, Roger E. McLendon, Anita B. Hjelmeland, Jeremy N. Rich
Journal: Cancer Research (2008)

Malignant gliomas are lethal cancers that display striking cellular heterogeneity. A highly tumorigenic glioma tumor subpopulation, termed cancer stem cells or tumor-initiating cells, promotes therapeutic resistance and tumor angiogenesis. Therefore, targeting cancer stem cells may improve patient survival. We interrogated the role of a neuronal cell adhesion molecule, L1CAM, in glioma stem cells as L1CAM regulates brain development and is expressed in gliomas. L1CAM(+) and CD133(+) cells cosegregated in gliomas, and levels of L1CAM were higher in CD133(+) glioma cells than normal neural progenitors. Targeting L1CAM using lentiviral-mediated short hairpin RNA (shRNA) interference in CD133(+) glioma cells potently disrupted neurosphere formation, induced apoptosis, and inhibited growth specifically in glioma stem cells. We identified a novel mechanism for L1CAM regulation of cell survival as L1CAM knockdown decreased expression of the basic helix-loop-helix transcription factor Olig2 and up-regulated the p21(WAF1/CIP1) tumor suppressor in CD133(+) glioma cells. To determine if targeting L1CAM was sufficient to reduce glioma stem cell tumor growth in vivo, we targeted L1CAM in glioma cells before injection into immunocompromised mice or directly in established tumors. In each glioma xenograft model, shRNA targeting of L1CAM expression in vivo suppressed tumor growth and increased the survival of tumor-bearing animals. Together, these data show that L1CAM is required for maintaining the growth and survival of CD133(+) glioma cells both in vitro and in vivo, and L1CAM may represent a cancer stem cell-specific therapeutic target for improving the treatment of malignant gliomas and other brain tumors.
Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.
Authors: P Kaplan, M Hendrikx, M Mattheussen, K Mubagwa, W Flameng
Journal: Circulation Research (1992)

To investigate the mechanism underlying postischemic cardiac dysfunction (myocardial stunning), contractility and adenine nucleotide metabolism were studied in three groups of isolated perfused rabbit hearts (control, ischemic, and reperfused), whereas Ca2+ uptake by the sarcoplasmic reticulum (SR) was measured in homogenates obtained from them. The hearts were Langendorff-perfused under constant pressure with Krebs-Henseleit solution at 37 degrees C. Global normothermic ischemia was produced by closing the perfusion line. In the reperfused group, after 15 minutes of ischemia, Krebs-Henseleit solution was perfused for 10 minutes. Developed left ventricular pressure (control, 104 +/- 6.3 mm Hg) and left ventricular dP/dt (2,063 +/- 256.6 mm Hg.sec-1) were significantly decreased in reperfused hearts (left ventricular pressure, 78 +/- 5.9 mm Hg; left ventricular dP/dt, 1,339 +/- 216.3 mm Hg.sec-1). Myocardial ATP content (control, 13.6 +/- 0.98 mumol/g dry wt) decreased during ischemia (4.5 +/- 1.23 mumol/g) but was restored to control level on reperfusion (11.8 +/- 0.68 mumol/g). Maximum velocity of Ca2+ uptake by the SR (Vmax) (control, 49.3 +/- 2.54 nmol.min-1 x mg-1) was significantly depressed by ischemia (36.3 +/- 1.94 nmol.min-1 x mg-1) but was restored to the control value after a 10-minute reperfusion (45.3 +/- 0.79 nmol.min-1 x mg-1). Apparent dissociation constant KCa and the Hill coefficient for Ca2+ uptake were not different between control, ischemia, and reperfusion. To test for the possible role of the SR Ca(2+)-release channel in the effect of ischemia and reperfusion, we measured Ca2+ uptake after incubation of homogenates with 610 microM ryanodine.(ABSTRACT TRUNCATED AT 250 WORDS)
Expression of Hirudin Fusion Proteins in Mammalian Cells
Authors: Kristian Riesbeck, Daxin Chen, Geoffrey Kemball-Cook, John H. McVey, Andrew J. T. George, Edward G. D. Tuddenham, Anthony Dorling, Robert I. Lechler
Journal: Circulation (1998)

Intravascular thrombosis occurs in disorders of diverse pathogeneses, including allograft and xenograft rejection. In this in vitro study, we describe an approach for tethering the specific thrombin inhibitor hirudin to plasma membranes as part of a genetic strategy for regulating intravascular coagulation.An HLA class I leader sequence was fused with hirudin linked to domains 3 and 4 of human CD4 and intracytoplasmic sequence from either CD4 or human P-selectin. The constructs were transfected into mouse fibroblasts, Chinese hamster ovary (CHO)-K1 cells, immortalized porcine endothelial cells (IPECs), and a pituitary secretory cell line (D16/16). Thrombin binding to the hirudin fusion proteins expressed on fibroblasts and CHO-K1 cells could be blocked by an anti-hirudin monoclonal antibody and by pretreatment of thrombin with either the synthetic tripeptide thrombin inhibitor PPACK or native hirudin. Hirudin expression significantly modified the procoagulant phenotype of IPECs in human plasma, leading to prolongation of clotting times. Hirudin-CD4-P-selectin fusion proteins accumulated in adrenocorticotropic hormone-containing granules in D16/16 cells, with no cell surface expression except on activation with phorbol ester, when hirudin relocated to the outer membrane.Hirudin fusion proteins were expressed on mammalian cells, where they reduced local thrombin levels and inhibited fibrin formation. Regulated expression was achieved on activated cells by use of the cytoplasmic sequence from P-selectin. In vivo, these fusion proteins may prove useful transgenic or gene therapy agents for preventing intravascular thrombosis.
Apolipoprotein AI and High-Density Lipoprotein Have Anti-Inflammatory Effects on Adipocytes via Cholesterol Transporters
Authors: Tomio Umemoto, Chang Yeop Han, Poulami Mitra, Michelle M. Averill, Chongren Tang, Leela Goodspeed, Mohamed Omer, Savitha Subramanian, Shari Wang, Laura J. Den Hartigh, Hao Wei, Eung Ju Kim, Jinkyu Kim, Kevin D. O’Brien, Alan Chait
Journal: Circulation Research (2013)

Macrophage accumulation in adipose tissue associates with insulin resistance and increased cardiovascular disease risk. We previously have shown that generation of reactive oxygen species and monocyte chemotactic factors after exposure of adipocytes to saturated fatty acids, such as palmitate, occurs via translocation of NADPH oxidase 4 into lipid rafts (LRs). The anti-inflammatory effects of apolipoprotein AI (apoAI) and high-density lipoprotein (HDL) on macrophages and endothelial cells seem to occur via cholesterol depletion of LRs. However, little is known concerning anti-inflammatory effects of HDL and apoAI on adipocytes.To determine whether apoAI and HDL inhibit inflammation in adipocytes and adipose tissue, and whether this is dependent on LRs.In 3T3L-1 adipocytes, apoAI, HDL, and methyl-β-cyclodextrin inhibited chemotactic factor expression. ApoAI and HDL also disrupted LRs, reduced plasma membrane cholesterol content, inhibited NADPH oxidase 4 translocation into LRs, and reduced palmitate-induced reactive oxygen species generation and monocyte chemotactic factor expression. Silencing ATP-binding cassette A-1 abrogated the effect of apoAI, but not HDL, whereas silencing ATP-binding cassette G-1 or scavenger receptor B-1 abrogated the effect of HDL but not apoAI. In vivo, apoAI transgenic mice fed a high-fat, high-sucrose, cholesterol-containing diet showed reduced chemotactic factor and proinflammatory cytokine expression and reduced macrophage accumulation in adipose tissue.ApoAI and HDL have anti-inflammatory effects in adipocytes and adipose tissue similar to their effects in other cell types. These effects are consistent with disruption and removal of cholesterol from LRs, which are regulated by cholesterol transporters, such as ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1.
Low-Density Lipoprotein Level Reduction by the 3-Hydroxy-3-Methylglutaryl Coenzyme-A Inhibitor Simvastatin Is Accompanied by a Related Reduction of F <sub>2</sub> -Isoprostane Formation in Hypercholesterolemic Subjects
Authors: Raffaele De Caterina, Francesco Cipollone, Francesca Paola Filardo, Marco Zimarino, Walter Bernini, Guido Lazzerini, Tonino Bucciarelli, Angela Falco, Paola Marchesani, Raffaella Muraro, Andrea Mezzetti, Giovanni Ciabattoni
Journal: Circulation (2002)

Background— Both statins and vitamin E, by reducing the rate of lipid peroxidation, may interfere with oxidative stress, but the impact of their combination is unknown. Methods and Results— We randomized 43 hypercholesterolemic patients (21 men, 22 women, age 63±11 years) to either simvastatin, to achieve &gt;20% reduction of total cholesterol, or simvastatin plus 600 mg/d vitamin E for 2 months. Patients were then crossed over to the alternative treatment. Lipid parameters documented patients’ compliance to simvastatin, whereas plasma levels of vitamin E documented compliance and absorption of vitamin E. We assessed urinary excretion of the isoprostane 8-iso-prostaglandin F 2α (8-iso-PGF 2α ) as an in vivo index of oxidative stress at baseline and after each month of therapy. 8-Iso-PGF 2α was significantly reduced by simvastatin, from 361±148 pg/mg creatinine (mean±SD) at baseline to 239±124 pg/mg creatinine after 1 month. The addition of vitamin E did not reduce such levels any further (256±125 after 1 month). Linear regression analysis showed a weak inverse relationship of 8-iso-PGF 2α with vitamin E levels but a much stronger relationship with LDL cholesterol ( R 2 =0.162; P &lt;0.001). Conclusions— In hypercholesterolemic patients, LDL cholesterol is a major correlate of oxidative stress. Concomitant with LDL cholesterol reduction, simvastatin causes a drastic reduction of oxidative stress to a level that is not further reduced by the addition of vitamin E. Results of clinical trials with vitamin E may have been hampered by inadequate knowledge of the background level of lipid peroxidation, which is a major determinant of vitamin E bioactivity.
50 years of asthma: UK trends from 1955 to 2004
Authors: H Ross Anderson, R. Gupta, D. P Strachan, E. S Limb
Journal: Thorax (2006)

Trends in asthma indicators from population surveys (prevalence) and routine statistics (primary care, prescriptions, hospital admissions and mortality) in the UK were reviewed from 1955 to 2004. The prevalence of asthma increased in children by 2 to 3-fold, but may have flattened or even fallen recently. Current trends in adult prevalence are flat. The prevalence of a life-time diagnosis of asthma increased in all age groups. The incidence of new asthma episodes presenting to general practitioners increased in all ages to a plateau in the mid 1990s and has declined since. During the 1990s, the annual prevalence of new cases of asthma and of treated asthma in general practice showed no major change. Hospital admissions increased from the early 1960s, more so in children, until the late 1980s and have fallen since. Asthma mortality showed two waves, a shorter and more intense one in the mid 1960s and a longer and less intense one in the late 1970s and early 1980s. The relative roles of diagnostic transfer, coding changes, medical care and epidemiological factors are discussed.
Creating a Healthier Future Through Early Interventions for Children
Authors: James A. Mercy, Janet Saul
Journal: JAMA (2009)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Modulation of tau phosphorylation by environmental copper
Authors: Kellen Voss, Christopher Harris, Martina Ralle, Megan Duffy, Charles Murchison, Joseph F Quinn
Journal: Translational Neurodegeneration (2014)

The transition metal copper enhances amyloid β aggregation and neurotoxicity, and in models of concomitant amyloid and tau pathology, copper also promotes tau aggregation. Since it is not clear if the effects of environmental copper upon tau pathology are dependent on the presence of pathological amyloid β, we tested the effects of copper overload and complexing in disease models which lack pathological amyloid β. We used cell culture and transgenic murine models to test the effects of environmental copper on tau phosphorylation. We used oral zinc acetate as a copper lowering agent in mice and examined changes in blood and brain metals through inductively coupled plasma mass spectroscopy. Behavioral effects of copper lowering were assessed with Morris water maze and novel object recognition tasks. Changes in tau phosphorylation were examined by phosphorylation specific antibodies on Western blots. In human neuroblastoma cells, excess copper promoted tau phosphorylation and a copper complexing agent, tetrathiomolybdate, attenuated tau phosphorylation. In a transgenic mouse model expressing wild type human tau, copper-lowering by oral zinc suppressed plasma and brain levels of copper, and resulted in a marked attenuation of tau phosphorylation. No significant changes in behavior were observed with copper lowering, but a trend to improved recognition of the novel object was observed in zinc acetate treated mice. We propose that reduction of brain copper by blocking uptake of copper from the diet may be a viable strategy for modulating tau pathology in Alzheimer’s disease. The potential benefits of this approach are tempered by the absence of a behavioral benefit and by the health risks of excessive lowering of copper.
Choosing Appropriate Substitution Models for the Phylogenetic Analysis of Protein-Coding Sequences
Authors: Beth Shapiro, Andrew Rambaut, Alexei J. Drummond
Journal: Molecular Biology and Evolution (2005)

Although phylogenetic inference of protein-coding sequences continues to dominate the literature, few analyses incorporate evolutionary models that consider the genetic code. This problem is exacerbated by the exclusion of codon-based models from commonly employed model selection techniques, presumably due to the computational cost associated with codon models. We investigated an efficient alternative to standard nucleotide substitution models, in which codon position (CP) is incorporated into the model. We determined the most appropriate model for alignments of 177 RNA virus genes and 106 yeast genes, using 11 substitution models including one codon model and four CP models. The majority of analyzed gene alignments are best described by CP substitution models, rather than by standard nucleotide models, and without the computational cost of full codon models. These results have significant implications for phylogenetic inference of coding sequences as they make it clear that substitution models incorporating CPs not only are a computationally realistic alternative to standard models but may also frequently be statistically superior.
Immunotherapy of Malignant Disease with Tumor Antigen–Specific Monoclonal Antibodies
Authors: Michael Campoli, Robert Ferris, Soldano Ferrone, Xinhui Wang
Journal: Clinical Cancer Research (2009)

Abstract A few tumor antigen (TA)–specific monoclonal antibodies (mAb) have been approved by the Food and Drug Administration for the treatment of several major malignant diseases and are commercially available. Once in the clinic, mAbs have an average success rate of ∼30% and are well tolerated. These results have changed the face of cancer therapy, bringing us closer to more specific and more effective biological therapy of cancer. The challenge facing tumor immunologists at present is represented by the identification of the mechanism(s) underlying the patients' differential clinical response to mAb-based immunotherapy. This information is expected to lead to the development of criteria to select patients to be treated with mAb-based immunotherapy. In the past, in vitro and in vivo evidence has shown that TA-specific mAbs can mediate their therapeutic effect by inducing tumor cell apoptosis, inhibiting the targeted antigen function, blocking tumor cell signaling, and/or mediating complement- or cell-dependent lysis of tumor cells. More recent evidence suggests that TA-specific mAb can induce TA-specific cytotoxic T-cell responses by enhancing TA uptake by dendritic cells and cross-priming of T cells. In this review, we briefly summarize the TA-specific mAbs that have received Food and Drug Administration approval. Next, we review the potential mechanisms underlying the therapeutic efficacy of TA-specific mAbs with emphasis on the induction of TA-specific cellular immune responses and their potential to contribute to the clinical efficacy of TA-specific mAb-based immunotherapy. Lastly, we discuss the potential negative effect of immune escape mechanisms on the clinical efficacy of TA-specific mAb-based immunotherapy. Clin Cancer Res; 16(1); 11–20
Nonspecific Cation Current Associated with Native Polycystin-2 in HEK-293 Cells
Authors: Bruna Pelucchi, Gianluca Aguiari, Angela Pignatelli, Elisa Manzati, Ralph Witzgall, Laura del Senno, Ottorino Belluzzi
Journal: Journal of the American Society of Nephrology (2006)

Mutations in either PKD1 or PKD2 gene are associated with autosomal dominant polycystic kidney disease, the most common inherited kidney disorder. Polycystin-2 (PC2), the PKD2 gene product, and the related protein polycystin-L, function as Ca(2+)-permeable, nonselective cation channels in different expression systems. This work describes a nonspecific cation current (I(CC)) that is present in native HEK-293 cells and highly associated with a PC2-channel activity. The current is voltage dependent, activating for potentials that are positive to -50 mV and inactivating in a few milliseconds. It is sensitive to Cd(2+), Gd(3+), La(3+), SKF96365, and amiloride. After silencing of PC2 by RNA interfering, cells show a reduced current that is restored by transfection with normal but not truncated PC2. Consistently, I(CC) is abolished by perfusion with an anti-PC2 antibody. Furthermore, heterologous expression of the PC1 cytoplasmic tail significantly increases I(CC) peak amplitude compared with native cells. This is the first characterization of such a current in HEK-293 cells, a widely used expression system for ion channels. These cells, therefore, could be regarded as a suitable and readily accessible tool to study interactions between native PC2/PC1 complex and other membrane proteins, thus contributing to the understanding of autosomal dominant polycystic kidney disease pathogenesis.