tbuckley/cabot-search huggingface dataset:
Combinatorial drug screening identifies synergistic co-targeting of Bruton’s tyrosine kinase and the proteasome in mantle cell lymphoma
Authors: M Axelrod, Z Ou, L K Brett, L Zhang, E R Lopez, A T Tamayo, V Gordon, R J Ford, M E Williams, L V Pham, M J Weber, M L Wang
Journal: Leukemia (2013)

Combinatorial drug screening identifies synergistic co-targeting of Bruton’s tyrosine kinase and the proteasome in mantle cell lymphoma
P143Targeting the mitochondrial fission proteins, MiD49 and MiD51, as a therapeutic strategy for cardioprotection
Authors: P Samangouei, JM Elder, N Burke, A Hall, DJ Hausenloy
Journal: Cardiovascular Research (2014)

Background: Ischaemic heart disease is the major cause of morbidity and mortality worldwide. Novel therapeutic strategies are essential to protect the heart from acute ischaemia-reperfusion injury (IRI). It has been reported that inhibiting mitochondrial fission, protects the heart against cardiomyocyte death during acute IRI. We investigated the mitochondrial fission proteins, MiD49 and MiD51, as novel targets for cardioprotection,
The chemokine receptor 5 Δ32 mutation is associated with increased renal survival in patients with IgA nephropathy
Authors: U.L.F. Panzer, Andr Schneider, Oliver M. Steinmetz, Ulrich Wenzel, Petra Barth, Rdiger Reinking, Jan U. Becker, Sigrid Harendza, Gunther Zahner, Michael Fischereder, Bernhard H. Kramer, Detlef Schlondorff, Tammo Ostendorf, Jrgen Floege, U.D.O. Helmchen, Rolf A.K. Stahl
Journal: Kidney International (2004)
Reduction of heat-shock protein-70 after prolonged treatment with retinoids: Biological and clinical implications
Authors: Patrizia Tosi, Giuseppe Visani, Emanuela Ottaviani, Davide Gibellini, Annalisa Pellacani, Sante Tura
Journal: American Journal of Hematology (1997)

Heat shock proteins (HSPs) are a group of highly conserved polypeptides involved in cellular response to heat or other physical or chemical stresses. It has been recently reported that HSPs could play a role in cellular differentiation. In this study we have evaluated, by a cytofluorimetric method, the presence of HSP-70 in HL-60 cells during treatment with all-trans retinoic acid (ATRA), 9-cis retinoic acid (9-cis RA), and 13-cis retinoic acid (13-cis RA). After 1 and 3 days of incubation at 10(-7) M, HSP-70 did not show any variation compared to control; prolonging the exposure, together with the appearance of cellular differentiation along the granulocytic pathway and apoptosis, a progressive decrease of HSP-70 was observed that, after 8 days of treatment, was reduced by 40% with ATRA and by 28% with 9-cis RA compared to untreated samples, while only minimal changes were evident by incubating the cells with 13-cis RA. Reduction of HSP-70 was not associated with decreased protein synthesis, as demonstrated by [3H] leucine incorporation. Double labeling with propidium iodide showed a decrease in HSP-70 in all the phases of the cell cycle concomitant with a reduced percentage of cycling cells in ATRA-treated samples. Dot blot and Northern blot analysis demonstrated no change in HSP-70 mRNA after retinoid treatment, thus suggesting a post-transcriptional regulation of the phenomenon. This reduced production of HSP-70 caused by ATRA and by 9-cis RA, though to a lesser extent, could render the cells more sensitive to cytotoxic agents and could provide the rationale for the efficacy of ATRA + chemotherapy combinations.
Drug Delivery: Ultrasound‐Triggered Regulation of Blood Glucose Levels Using Injectable Nano‐Network (Adv. Healthcare Mater. 6/2014)
Authors: Jin Di, Jennifer Price, Xiao Gu, Xiaoning Jiang, Yun Jing, Zhen Gu
Journal: Advanced Healthcare Materials (2014)

On page 811, Y. Jing, Z. Gu and co-workers present the integration of an injectable nano-network with a focused ultrasound system (FUS) which can remotely regulate insulin release both in vitro and in vivo. Serving as a synthetic insulin reservoir, the nano-network consisting of adhesive biodegradable nanoparticles promotes insulin release upon FUS triggers in a pulsatile, remote and non-invasive control manner. Image courtesy of Dwayne Martin.
Intrapericardial Tetracycline for the Management of Cardiac Tamponade Secondary to Malignant Pericardial Effusion
Authors: Stephen Davis, Surendra M. Sharma, Edwin D. Blumberg, Chung S. Kim
Journal: New England Journal of Medicine (1978)

CARDIAC tamponade is an acute, life-threatening complication of malignant pericardial effusions. There have been conflicting views on the management of this clinical situation1; traditionally, the approach has been surgical, with establishment of a pericardial window, or conservative, pericardiocentesis with local instillation of chemotherapeutic agents being used. A recent review of the literature by Smith et al.2 suggests that conservative therapy is safer and associated with a longer symptom-free interval. Mechlorethamine (nitrogen mustard), thiophosphoramide (thiotepa) and quinacrine (Atabrine) are the most commonly used agents for intrapericardial instillation. However, these agents cause severe pain, and the alkylating agents cause bone-marrow toxicity. . . .
Autophagy in Hypothalamic AgRP Neurons Regulates Food Intake and Energy Balance
Authors: Susmita Kaushik, Jose Antonio Rodriguez-Navarro, Esperanza Arias, Roberta Kiffin, Srabani Sahu, Gary J. Schwartz, Ana Maria Cuervo, Rajat Singh
Journal: Cell Metabolism (2011)

SummaryMacroautophagy is a lysosomal degradative pathway that maintains cellular homeostasis by turning over cellular components. Here we demonstrate a role for autophagy in hypothalamic agouti-related peptide (AgRP) neurons in the regulation of food intake and energy balance. We show that starvation-induced hypothalamic autophagy mobilizes neuron-intrinsic lipids to generate endogenous free fatty acids, which in turn regulate AgRP levels. The functional consequences of inhibiting autophagy are the failure to upregulate AgRP in response to starvation, and constitutive increases in hypothalamic levels of pro-opiomelanocortin and its cleavage product α-melanocyte-stimulating hormone that typically contribute to a lean phenotype. We propose a conceptual framework for considering how autophagy-regulated lipid metabolism within hypothalamic neurons may modulate neuropeptide levels to have immediate effects on food intake, as well as long-term effects on energy homeostasis. Regulation of hypothalamic autophagy could become an effective intervention in conditions such as obesity and the metabolic syndrome.Graphical abstractGraphical AbstractHighlights► Starvation induces hypothalamic autophagy ► Autophagy in AgRP neurons regulates food intake and energy balance ► Starvation-induced hypothalamic autophagy mobilizes lipid droplets ► Autophagy-derived free fatty acids increase hypothalamic AgRP levels
Thrombocytopenia Occurring during Heparin Therapy
Authors: William R. Bell
Journal: New England Journal of Medicine (1976)

Thrombocytopenia has recently been observed in a surprising number of patients during treatment with heparin. A report of five cases appears in this issue of the Journal. Discovered in 1915, heparin has been extensively used in clinical medicine since the mid-1930's. Apart from hemorrhagic complications attributable to the induced coagulation defect, untoward reactions have been infrequent. Rarely, patients with a past history of allergic disease have had immediate hypersensitivity reactions manifested by urticaria, rhinitis, asthma, fever, cyanosis, diaphoresis and hypotension. In some cases these reactions could be averted by use of heparin from another animal source. Severe thrombocytopenia occurring . . .
Endotoxin increases parathyroid hormone-related protein mRNA levels in mouse spleen. Mediation by tumor necrosis factor.
Authors: J L Funk, E J Krul, A H Moser, J K Shigenaga, G J Strewler, C Grunfeld, K R Feingold
Journal: Journal of Clinical Investigation (1993)

Parathyroid hormone-related protein (PTHrP) causes hypercalcemia in malignancy. However, the role and regulation of PTHrP in normal physiology is just beginning to be explored. PTHrP is found in the spleen and has several other features common to cytokines. Since endotoxin (LPS) causes many of its effects indirectly by inducing cytokines, studies were undertaken to determine whether LPS might also induce splenic PTHrP expression. LPS (100 ng/mouse) increased splenic PTHrP mRNA levels 3.6-fold in C3H/OuJ mice. This effect was maximal at 2 h and returned to baseline by 4 h. PTHrP peptide levels also increased 3.3-fold in splenic extracts in response to LPS (1 microgram/mouse). Murine TNF-alpha and human IL-1 beta, cytokines that mediate many of the effects of LPS, also increased splenic PTHrP mRNA levels. LPS-resistant C3H/HeJ mice, which produce minimal amounts of TNF and IL-1 in response to LPS, were resistant to LPS induction of splenic PTHrP mRNA, while TNF-alpha and IL-1 beta readily increased PTHrP mRNA levels in C3H/HeJ mice. Anti-TNF antibody blocked LPS induction of splenic PTHrP mRNA in C3H/OuJ mice by 68%, indicating that TNF is a mediator of the LPS induction of PTHrP levels. In contrast, an IL-1 receptor antagonist (IL-1ra) was ineffective. The increase in PTHrP in the spleen during the immune response suggests that PTHrP may play an important role in immune modulation, perhaps by mediating changes in lymphocyte proliferation and/or function.
Visualization of the Left Hepatic Lobe during Radioisotopic Venography/Lung Imaging with Technetium-99m MAA
Authors: KENNETH BARTOLD, MICHAEL FANCHER, REZA ABGHARI
Journal: Clinical Nuclear Medicine (1986)

An unusual case of uptake of radioisotope by the liver during radioisotope venography/lung imaging with Tc-99m MAA is presented. Abnormalities in venous circulation of the lower extremities and abdomen, perfusion of the lung, and structure of the liver were detected, and correlated with other studies performed on a single patient. The mechanisms of uptake of Tc-99m MAA by the liver are discussed, with special attention paid to the mechanism believed to be present in this case.
CASE OF MALIGNANT DISEASE OF OVARIES: SUDDEN DEATH
Authors: G. King
Journal: BMJ (1853)

water was then thrown into the house; but Hillier was not brought up for nearly an hour.on my ar1ia, about half an hour after Knee had been extricated, I found him respiinng feebly, much convulsed, and totally insensible.After ap lying the electro-galvanic current, at intervals, for half man our, he was able to articu- late, but remained insensible to what was going on around him for a long time.At length he recovered.As soon as Hillier was brought up, I inflated the lungs, and applied electro-galvanism for an hour and a half.
THE EFFECT OF AVITAMINOSIS-A ON THE PROSTATE
Authors: Robert A. Moore, Jerome Mark
Journal: The Journal of Experimental Medicine (1936)

1. Vitamin A deficiency alone in the white rat is associated with atrophy of the testis and accessory sexual glands. This would appear to be indicative of some disturbance in the hypophyseal-gonadalprostatic hormonal relationships. All of the known vitamins necessary for the rat, except vitamin A, were present in the diet fed the animals studied. 2. Vitamin A deficiency in the rat is associated with foci of inflammation and epithelial metaplasia in the prostatic acini and vesicular ducts entirely similar to that reported in other organs. 3. Focal metaplasia and inflammation is occasionally encountered in the prostate of patients with extreme inanition associated with stenosis of the esophagus. It seems probable that this lesion is due to vitamin A deficiency.
274 THE CRP LEVEL IS A GOOD PREDICTOR OF MORTALITY INDEPENDENT OF PUGH OR MELD SCORES IN PATIENTS WITH END STAGE LIVER DISEASE (ESLD)
Authors: O. Barbot, J.P. Cervoni, T. Thevenot, C. Richou, C. Vanlemmens, V. Di Martino
Journal: Journal of Hepatology (2008)
Nutrition and Nutritional Diseases: The Evolution of Concepts
Authors: William B. Bean
Journal: JAMA (1982)

The history of ideas is a matter of prime concern to scholars and scientists, but in few areas of medical and scientific history is it more confused and haphazard than in the field of nutrition. Despite this confusion, there have been significant advances in certain vital aspects. Perhaps the major lesson to learn is that each person's requirements for various essential food substances that cannot be manufactured by the body are unique, and we can quantify them only in rather crude ways. The impor<i>Continued on p 527</i>.<i>Continued from p 524</i>. tant concepts of average requirement and average allowances are often misinterpreted by the public. It is not likely that we will have available an analysis of each person's precise requirements of various substances. Small organisms that grow rapidly and can be isolated, such as yeast and bacteria, can have their nutrient medium varied to find which elements are
Circulating Interferon-like Viral Inhibitor in Patients with Meningitis Due to<i>Haemophilus influenzae</i>
Authors: Richard H. Michaels, Miles M. Weinberger, Monto Ho
Journal: New England Journal of Medicine (1965)

IT has been reported that other materials than viruses may induce the formation of interferon.1 , 2 In particular, interferon-like viral inhibitors have been produced by gram-negative bacteria in chickens1 and mice3 and by bacterial endotoxins in mice3 and in rabbits.4 These results in animals suggested to us the possibility that an interferon-like viral inhibitor would also develop in human patients with gram-negative bacteremia or with endotoxemia. The present report describes the demonstration of such an inhibitor in 2 patients with meningitis and bacteremia caused by Haemophilus influenzae. Materials and MethodsGeneralSerial blood samples were obtained by venipuncture, and serums were . . .
Reaffirmation of the Auriculoventricular Conduction System in Man
Authors: JOHN L. READ, ERLING S. HEGRE, SIMON RUSSI
Journal: Circulation (1953)

Gross and microscopic studies of the auriculoventricular conduction system were performed in 60 human hearts. A unique technic is introduced which will produce a photographic record of undistorted serial sections through a block containing the auriculoventricular node, auriculoventricular bundle and branches. By projecting the completed film as a motion picture, the course and changing relationships of component structures can be followed from level to level in uninterrupted sequence. The neurogenic versus the myogenic concept of cardiac conduction is reviewed at length.
Novel CD4+ and CD8+ T-cell determinants within the NS3 protein in subjects with spontaneously resolved HCV infection
Authors: Anne M. Wertheimer, Camette Miner, David M. Lewinsohn, Anna W. Sasaki, Ezra Kaufman, Hugo R. Rosen
Journal: Hepatology (2003)

Spontaneous resolution of hepatitis C virus (HCV) infection is a relatively infrequent event, and these individuals provide a unique opportunity to characterize correlates of protective immunity as an important first step in the development of vaccine candidates. The aim of this study was to directly and comprehensively enumerate HCV–nonstructural protein 3 (NS3) specific CD4 + and CD8 + T cells ex vivo from HLA diverse individuals who had been successful in spontaneously resolving HCV infection. We measured interferon gamma (IFN–γ) production with an ELISPOT assay using magnetic bead–separated CD4 + or CD8 + T cells in response to autologous DCs that had been pulsed with 15mer per peptides overlapping by 11 amino acids and spanning all of the NS3 protein (150 total peptides). All subjects with spontaneously recovered HCV infection demonstrated vigorous and multispecific CD4 + T–cell responses to NS3 peptides, and 6 of 10 subjects demonstrated CD8 + T–cell responses. More importantly, we identified novel, previously unpredicted antigenic regions, which in most cases elicited high frequencies within a given individual. In conclusion, subjects who have spontaneously eradicated HCV infection up to 35 years earlier demonstrate persistent CD4 + and CD8 + T–cell responses specific to NS3. By providing a comprehensive screening of all potential T–cell epitopes contained in the NS3 region, our strategy defines the breadth of the T–cell response and identifies novel, unpredicted specificities.
Aberrant Activation of Notch Signaling in Human Breast Cancer
Authors: Spyros Stylianou, Rob B. Clarke, Keith Brennan
Journal: Cancer Research (2006)

Abstract A role for Notch signaling in human breast cancer has been suggested by both the development of adenocarcinomas in the murine mammary gland following pathway activation and the loss of Numb expression, a negative regulator of the Notch pathway, in a large proportion of breast carcinomas. However, it is not clear currently whether Notch signaling is frequently activated in breast tumors, and how it causes cellular transformation. Here, we show accumulation of the intracellular domain of Notch1 and hence increased Notch signaling in a wide variety of human breast carcinomas. In addition, we show that increased RBP-Jκ–dependent Notch signaling is sufficient to transform normal breast epithelial cells and that the mechanism of transformation is most likely through the suppression of apoptosis. More significantly, we show that attenuation of Notch signaling reverts the transformed phenotype of human breast cancer cell lines, suggesting that inhibition of Notch signaling may be a therapeutic strategy for this disease. (Cancer Res 2006; 66(3): 1517-25)
Aberrant Activation of Fatty Acid Synthesis Suppresses Primary Cilium Formation and Distorts Tissue Development
Authors: Nicolas Willemarck, Evelien Rysman, Koen Brusselmans, Griet Van Imschoot, Frank Vanderhoydonc, Katrien Moerloose, Evelyne Lerut, Guido Verhoeven, Frans van Roy, Kris Vleminckx, Johannes V. Swinnen
Journal: Cancer Research (2010)

Abstract Aberrant activation of fatty acid synthesis is a key feature of many advanced human cancers. Unlike in classical lipogenic tissues, this process has been implicated in membrane production required for rapid cell proliferation. Here, to gain further insight into the consequences of tumor-associated fatty acid synthesis, we have mimicked the lipogenic phenotype of cancer cells in Xenopus embryos by microinjection of RNA encoding the lipogenic transcription factor sterol regulatory element binding protein 1c (SREBP1c). Dramatic morphologic changes were observed that could be linked to alterations in Wnt and Hedgehog signaling, and ultimately to a distortion of the primary cilium. This is a sophisticated microtubular sensory organelle that is expressed on the surface of nearly every cell type and that is lost in many cancers. SREBP1c-induced loss of the primary cilium could be confirmed in mammalian Madin-Darby canine kidney (MDCK) cells and was mediated by changes in the supply of fatty acids. Conversely, inhibition of fatty acid synthesis in highly lipogenic human prostate cancer cells restored the formation of the primary cilium. Lipid-induced ciliary loss was associated with mislocalization of apical proteins, distortion of cell polarization, and aberrant epithelial tissue development as revealed in three-dimensional cultures of MDCK cells and in the developing mouse prostate. These data imply that tumor-associated lipogenesis, in addition to rendering cells more autonomous in terms of lipid supply, disturbs cilium formation and contributes to impaired environmental sensing, aberrant signaling, and distortion of polarized tissue architecture, which are all hallmarks of cancer. Cancer Res; 70(22); 9453–62. ©2010 AACR.
Diffuse Bone Marrow Involvement of Hodgkin Lymphoma Mimics Hematopoietic Cytokine-Mediated FDG uptake on FDG PET Imaging
Authors: Stephen B. Chiang, Alan Rebenstock, Liang Guan, Abass Alavi, Hongming Zhuang
Journal: Clinical Nuclear Medicine (2003)

Whole-body fluorine-18 fluorodeoxyglucose (F-18 FDG) positron emission tomography (PET) has been useful in the management of a variety of malignancies. In patients with chemotherapy followed by bone marrow stimulants such as granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, the bone marrow will have diffuse, increased FDG accumulation. Therefore, diffuse bone marrow FDG uptake is commonly attributable to the effect of hematopoietic cytokines. However, diffuse bone marrow FDG uptake can also be caused by bone marrow involvement by malignancy. The authors report a patient with diffuse bone marrow involvement of Hodgkin disease that appears indistinguishable from hematopoietic cytokine-mediated FDG bone marrow uptake.
From general policy to legal rule: aspirations and limitations of the precautionary principle.
Authors: Gary E Marchant
Journal: Environmental Health Perspectives (2003)

The rapid spread of the precautionary principle (PP) demonstrates the need to explicitly address the role of precaution in environmental decision making. Unfortunately, the PP in its current form is limited by the vagueness of, and variations in, the many formulations of the PP. This ambiguity in the meaning of the PP would not be so serious if the PP were limited to a general aspirational policy, but in every jurisdiction that has adopted the PP it has been transformed rapidly into a binding legal rule. As a legal rule, the ambiguity of the PP results in arbitrary application by regulatory agencies and reviewing courts and limits the capability of reviewing courts to perform their function in overseeing agency actions. To improve the explicit application of precaution, we must go beyond the current form of the PP and attempt to define the factors that weigh in favor of more or less precaution for specific risks.
A computer program based on parallel line assay for analysis of skin tests
Authors: S. Martin, P. Cuesta, P. Rico, C. Cortés
Journal: Allergy (1997)

A computer program for the analysis of differences or changes in skin sensitivity has been developed. It is based on parallel line assay, and its main features are its ability to conduct a validation process which ensures that the data from skin tests conform to the conditions imposed by the analysis which is carried out (regression, parallelism, etc.), the estimation of the difference or change in skin sensitivity, and the determination of the 95% and 99% confidence intervals of this estimation. This program is capable of managing data from independent groups, as well as paired data, and it may be applied to the comparison of allergen extracts, with the aim of determining their biologic activity, as well as to the analysis of changes in skin sensitivity appearing as a consequence of treatment such as immunotherapy.
Mycobacterial diseases developed during anti-tumour necrosis factor-α therapy
Authors: Jung-Wan Yoo, Kyung-Wook Jo, Bo-Hyung Kang, Mi Young Kim, Bin Yoo, Chang-Keun Lee, Yong-Gil Kim, Suk-Kyun Yang, Jeong-Sik Byeon, Kyung-Jo Kim, Byong Duk Ye, Tae Sun Shim
Journal: European Respiratory Journal (2014)

Nontuberculous mycobacterial (NTM) disease and tuberculosis (TB) develop during anti-tumour necrosis factor (TNF)-α therapy. We compared clinical characteristics and outcomes between the two diseases. A total of 1165 patients were screened for TB and treated with TNF-α antagonists from July 2004 to July 2013 for the following conditions: inflammatory bowel disease (n = 422), rheumatoid arthritis (n = 320), and ankylosing spondylitis (n = 389). TB and NTM disease were diagnosed at baseline screening in four and three patients, respectively, and developed during anti-TNF-α therapy in 19 and six patients, respectively. The incidence rate of TB and NTM disease was 747.7 per 100 000 and 238.2 per 100 000 person-years, respectively. Patients with NTM disease were older, with a greater proportion of females. All cases of NTM disease involved the lung, with rheumatoid arthritis (83.3%) being the most frequent underlying disease. The most common radiological feature was consolidation in NTM disease, and honeycombing was present in two rheumatoid arthritis patients with NTM disease. The most common pathogen was Mycobacterium intracellulare (n = 3) followed by Mycobacterium avium (n = 2). Both the NTM and TB group showed favourable outcomes. The clinical characteristics differed between NTM disease and TB that developed on anti-TNF-α agents, but clinical outcomes were favourable in both diseases.