tbuckley/cabot-search huggingface dataset:
The Effect of Insulin on the Alpha-Cell Response to Hyperglycemia in Long-Standing Alloxan Diabetes
Authors: Jan T. Braaten, Gerald R. Faloona, Roger H. Unger
Journal: Journal of Clinical Investigation (1974)

In acute experimental diabetes in animals, alpha-cell unresponsiveness to hyperglycemia can be promptly corrected by insulin, but in human diabetes, even massive doses of insulin have little effect. To determine if this inability of insulin to correct the alpha-cell abnormality in man is merely the consequence of the long duration of the diabetic state (rather than of a difference in mechanism), the effect of insulin was studied in alloxan diabetes of long duration. Alloxan-diabetic dogs were maintained for 7-18 mo and treated daily with insulin. When glucose was infused without insulin, glucagon did not decline but rose paradoxically. However, when insulin was infused at a rate of 9 mU/kg/min together with glucose, a prompt decline in glucagon from a base-line average of 171 pg/ml SEM+/-34 to a nadir of 41 pg/ml SEM+/-9 was observed. This decline indicated that alpha-cell responsiveness to hyperglycemia is completely restored by large quantities of insulin. To determine if small amounts of insulin would similarly restore alpha-cell responsiveness in long-standing experimental diabetes, 1.4 mU/kg/min was infused. By the time the mean insulin level had risen 43 muU/ml, glucagon had declined significantly and ultimately fell to a nadir of 44 pg/ml. It is concluded from these studies that alpha-cell responsiveness to hyperglycemia can be fully restored in long-standing alloxandiabetic dogs as readily as in acutely diabetic dogs. Its ineffectiveness in restoring alpha-cell responsiveness to hyperglycemia in human diabetes may not, therefore, be related to duration of the diabetic state, and may reflect a primary alpha-cell defect.
Intracerebral injection of proinflammatory cytokines or leukocyte chemotaxins induces minimal myelomonocytic cell recruitment to the parenchyma of the central nervous system.
Authors: P B Andersson, V H Perry, S Gordon
Journal: The Journal of Experimental Medicine (1992)

Neither excitotoxic neurodegeneration nor lipopolysaccharide induces an acute myelomonocytic exudate in the murine central nervous system (CNS) parenchyma (Andersson, P.-B., V. H. Perry, and S. Gordon. 1991. Neuroscience, 42:201; Andersson, P.-B., V. H. Perry, and S. Gordon. 1992. Neuroscience 48:169). In this study formyl-methionyl-leucyl-phenylalanine, platelet-activating factor, interleukin 8 (IL-8), IL-1, or tumor necrosis factor alpha were injected into the hippocampus to assess whether these leukocyte chemotaxins and known mediators of recruitment could bypass this block. They induced morphologic activation of microglia and widespread leukocyte margination but little or no cell exudation into the CNS parenchyma. By contrast, there was acute myelomonocytic cell recruitment to the choroid plexus, meninges, and ventricular system, comparable to that in the skin after subcutaneous injection. The normal CNS parenchyma appears to be a tissue unique in its resistance to leukocyte diapedesis, which is shown here to be at a step beyond chemotactic cytokine secretion or induction of leukocyte adhesion to cerebral endothelium.
Sequential Gene Targeting to Make Chimeric Tumor Models with <i>De Novo</i> Chromosomal Abnormalities
Authors: Jennifer S. Chambers, Tomoyuki Tanaka, Tim Brend, Hanif Ali, Nicola J. Geisler, Leah Khazin, Juan C. Cigudosa, T. Neil Dear, Kenneth MacLennan, Terence H. Rabbitts
Journal: Cancer Research (2014)

Abstract The discovery of chromosomal translocations in leukemia/lymphoma and sarcomas presaged a widespread discovery in epithelial tumors. With the advent of new-generation whole-genome sequencing, many consistent chromosomal abnormalities have been described together with putative driver and passenger mutations. The multiple genetic changes required in mouse models to assess the interrelationship of abnormalities and other mutations are severe limitations. Here, we show that sequential gene targeting of embryonic stem cells can be used to yield progenitor cells to generate chimeric offspring carrying all the genetic changes needed for cell-specific cancer. Illustrating the technology, we show that MLL–ENL fusion is sufficient for lethal leukocytosis and proof of genome integrity comes from germline transmission of the sequentially targeted alleles. This accelerated technology leads to a reduction in mouse numbers (contributing significantly to the 3Rs), allows fluorescence tagging of cancer-initiating cells, and provides a flexible platform for interrogating the interaction of chromosomal abnormalities with mutations. Cancer Res; 74(5); 1588–97. ©2014 AACR.
Changes in Amyloid-β and Tau in the Cerebrospinal Fluid of Transgenic Mice Overexpressing Amyloid Precursor Protein
Authors: Luis F. Maia, Stephan A. Kaeser, Julia Reichwald, Michael Hruscha, Peter Martus, Matthias Staufenbiel, Mathias Jucker
Journal: Science Translational Medicine (2013)

Changes in Aβ and Tau in the CSF of APP transgenic mice mirror the temporal sequence and magnitude of changes in these proteins in the CSF of Alzheimer’s disease patients.
Regional Cerebral low in Man Determined by Intral-artrial Injection of Radioactive Inert Gas
Authors: K. Høedt-Rasmussen, Edda Sveinsdottir, Niels A. Lassen
Journal: Circulation Research (1966)

The intra-arterial injection of a radioactive inert gas is described for measurement of regional cerebral blood flow in man from externally recorded clearance curves. The stochastic analysis for calculating the average cerebral blood flow in ml/100 g/min is compared to an analysis of the curve into two compartments with fast and slow clearance rates representing flow in grey and white cerebral matter respectively. An estimate of the relative weight of the grey matter in the cerebral region counted from brain is also obtained. A detailed description is given of the experimental procedure using krypton 85 or xenon 133 as the tracer gas. A brief injection time and short time constant in the recording ratemeter are important for obtaining a correct estimate of the maximal height of the curve. Mono-exponential extrapolation beyond the time of observation (usually 15 minutes) is employed. The practical procedure for calculating the results according to the stochastic and compartmental models are described with particular emphasis on the simple "10 minutes-average-flow-value, " CBF (10) which corresponds directly to the results of the classical Kety-Schmidt inert gas inhalation method for measurement of the average blood flow of the whole brain.
Polyethylene Terephthalate May Yield Endocrine Disruptors
Authors: Leonard Sax
Journal: Environmental Health Perspectives (2009)

BackgroundRecent reports suggest that endocrine disruptors may leach into the contents of bottles made from polyethylene terephthalate (PET). PET is the main ingredient in most clear plastic containers used for beverages and condiments worldwide and has previously been generally assumed not to be a source of endocrine disruptors.ObjectiveI begin by considering evidence that bottles made from PET may leach various phthalates that have been putatively identified as endocrine disruptors. I also consider evidence that leaching of antimony from PET containers may lead to endocrine-disrupting effects.DiscussionThe contents of the PET bottle, and the temperature at which it is stored, both appear to influence the rate and magnitude of leaching. Endocrine disruptors other than phthalates, specifically antimony, may also contribute to the endocrine-disrupting effect of water from PET containers.ConclusionsMore research is needed in order to clarify the mechanisms whereby beverages and condiments in PET containers may be contaminated by endocrine-disrupting chemicals.
The goblet cell: a key player in ischaemia-reperfusion injury
Authors: Malin E V Johansson, Gunnar C Hansson
Journal: Gut (2012)

The high number of bacteria in the intestine poses a constant threat to the host. Under normal homeostatic conditions, there is a bacteria-host balance, where all the bacteria are kept at a distance from direct contact with the host cells.1 The importance of mucus has been realised for a long time, but its organisation has only recently emerged. Importantly, the small and large intestine differ in mucus organisation and how the bacterial contact with the epithelium is minimised. In the colon, the inner and attached mucus layer act as an impenetrable barrier that does not allow bacteria to enter.1 On the contrary, the outer colon mucus layer is non-adherent and penetrable to bacteria, and as such makes up the natural habitat for the commensals. The small intestine has only one mucus layer2 into which bacteria can penetrate, but the bacteria are still kept away from the epithelium by the numerous antimicrobial peptides and proteins secreted, and the forward peristaltic movement of the mucus with its trapped bacteria.3 4

Many possibilities …
Opportunities for sudden death prevention: Directions for new clinical and basic research
Authors: R Myerburg
Journal: Cardiovascular Research (2001)

Sudden cardiac death (SCD) represents an enormous public health problem in all developed countries of the world, yet its magnitude and precise incidence in different populations and disease subgroups remains unclear. There also remain major questions and research challenges in establishing the sensitive and specific markers of SCD risk needed for optimizing therapeutic strategies and allocation of resources, such as implantable defibrillators. In the past, risk factors for coronary artery disease (CAD) have been heavily relied on to identify risk for SCD. However, although a majority of SCD events continue to occur in the context of this disease etiology, risk factors for CAD appear to have relatively limited ability to predict risk in specific individuals and subgroups with enhanced progressive or inherited susceptibility to lethal arrhythmias. This commentary is intended to assess potentials for progress in developing improved approaches to SCD prediction and prevention through new clinical and basic research on the fundamental causes of ventricular arrhythmias, the development of new markers of electrical instability, and better understanding of the role of genetic variability in their origin.
TCT-532 Economic Outcomes of Endovascular Femoropopliteal Intervention using Drug-Coated Balloons vs. Standard PTA: 1-year Results from the IN.PACT SFA II Trial
Authors: Adam C. Salisbury, Haiyan Li, Erin E. Notestein, Katherine A. Vilain, Michael Jaff, Peter Schneider, John R. Laird, David Cohen
Journal: Journal of the American College of Cardiology (2014)
The degree of spinal inflammation is similar in patients with axial spondyloarthritis who report high or low levels of disease activity: a cohort study
Authors: U Kiltz, X Baraliakos, P Karakostas, M Igelmann, L Kalthoff, C Klink, D Krause, E Schmitz-Bortz, M Flörecke, M Bollow, J Braun
Journal: Annals of the Rheumatic Diseases (2012)

The threshold for disease activity required to start antitumour necrosis factor (TNF) therapy has been arbitrarily set in patients with axial spondyloarthritis (axSpA) at Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4. How this relates to spinal inflammation is unknown.To systematically compare the clinical, laboratory and imaging data of patients with axSpA with respect to their BASDAI level.A total of 100 consecutive patients with axSpA who had never been treated with TNF blockers were included. Laboratory parameters, spinal MRI and x-rays were quantified. Data were stratified according to BASDAI ≥ 4.44 patients were diagnosed as non-radiographic axSpA (nraxSpA) and 56 patients as ankylosing spondylitis (AS): median age 40.3 ± 10.4 years; 57% male, mean disease duration since diagnosis 6.4 ± 8.4 years, 88% HLA-B27+, mean modified Stokes Ankylosing Spondylitis Spinal Score 8.3 ± 16.4. 60% of patients had spinal inflammation by MRI. The stratification based on BASDAI ≥ 4 disclosed significant differences in most clinical parameters but not for inflammation: patients with nraxSpA and BASDAI < 4 versus ≥ 4 had 0.9 ± 1.4 and 0.5 ± 0.6 inflammatory lesions/patient, respectively (p=0.6), while patients with AS had 3.6 ± 3.7 and 2.7 ± 3.0 inflammatory lesions/patient, respectively (p=0.4).The burden of inflammation is quite comparable in patients with axSpA-regardless of disease activity. These data clearly challenge the concept of the recommended cut-off point of BASDAI ≥ 4.
Differential expression of angiotensin receptors in human cutaneous wound healing
Authors: U.M. Steckelings, B.M. Henz, S. Wiehstutz, T. Unger, M. Artuc
Journal: British Journal of Dermatology (2005)

Angiotensin AT1 and AT2 receptors are expressed in human skin. Furthermore, AT2 receptors have been reported to be upregulated during tissue repair and remodelling in various noncutaneous human tissues.Detection of alterations in angiotensin II receptor expression during wound healing in human skin.Three models were employed. (i) Primary human keratinocytes were razor scraped in culture flasks and alterations in the expression of angiotensin receptor mRNA determined by semiquantitative reverse transcription-polymerase chain reaction for 1-12 h thereafter. (ii) Early wound healing (48 h after cutting) was studied in punch biopsies from human skin ex vivo by means of immunohistochemical staining using polyclonal antibodies against the AT1 or AT2 receptor. (iii) In vivo wound healing was studied in sections of human cutaneous scars by immunohistochemistry to determine receptor expression early (2 days) and late (2 weeks-3 months) after surgery.In all experimental settings, an upregulation of both receptor subtypes was noticed after wounding. Immunohistochemically stained skin sections showed a stronger expression of AT2 than of AT1 receptors within the area of scarring. Enhanced receptor expression was detectable as early as 24 h after injury and lasted for up to 3 months.From these data, we conclude that angiotensin AT1 and AT2 receptors are upregulated in human cutaneous wounds, giving further support to the concept that angiotensin II plays a role even at an early stage during cutaneous wound healing.
No Improvement of Patient or Graft Survival in Transplant Recipients Treated with Angiotensin-Converting Enzyme Inhibitors or Angiotensin II Type 1 Receptor Blockers
Authors: Gerhard Opelz, Martin Zeier, Gunter Laux, Christian Morath, Bernd Döhler
Journal: Journal of the American Society of Nephrology (2006)

It was reported recently that treatment of kidney transplant recipients with angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type 1 receptor blockers (ARB) is associated with strikingly improved long-term graft and patient survival. This finding has important implications for future posttransplantation therapy recommendations. In an analysis of 17,209 kidney and 1744 heart transplant recipients, an association of treatment with ACEI/ARB with improved transplant outcome could not be confirmed. It is concluded that recommendations for a widespread use of ACEI/ARB treatment in transplant recipients are unwarranted.
The Electrocardiographic Exercise Test in a Population with Reduced Workup Bias: Diagnostic Performance, Computerized Interpretation, and Multivariable Prediction
Authors: V F Froelicher, K G Lehmann, R Thomas, S Goldman, D Morrison, R Edson, P Lavori, J Myers, C Dennis, R Shabetai, D Do, J Froning
Journal: Annals of Internal Medicine (1998)

Empirical scores, computerized ST-segment measurements, and equations have been proposed as tools for improving the diagnostic performance of the exercise test.To compare the diagnostic utility of these scores, measurements, and equations with that of visual ST-segment measurements in patients with reduced workup bias.Prospective analysis.12 university-affiliated Veterans Affairs Medical Centers.814 consecutive patients who presented with angina pectoris and agreed to undergo both exercise testing and coronary angiography.Digital electrocardiographic recorders and angiographic calipers were used for testing at each site, and test results were sent to core laboratories.Although 25% of patients had previously had testing, workup bias was reduced, as shown by comparison with a pilot study group. This reduction resulted in a sensitivity of 45% and a specificity of 85% for visual analysis. Computerized measurements and visual analysis had similar diagnostic power. Equations incorporating nonelectrocardiographic variables and either visual or computerized ST-segment measurement had similar discrimination and were superior to single ST-segment measurements. These equations correctly classified 5 more patients of every 100 tested (areas under the receiver-operating characteristic curve, 0.80 for equations and 0.68 for visual analysis; P < 0.001) in this population with a 50% prevalence of disease.Standard exercise tests had lower sensitivity but higher specificity in this population with reduced work-up bias than in previous studies. Computerized ST-segment measurements were similar to visual ST-segment measurements made by cardiologists. Considering more than ST-segment measurements can enhance the diagnostic power of the exercise test.
A comparison of calcium currents in rat and guinea pig single ventricular cells.
Authors: I R Josephson, J Sanchez-Chapula, A M Brown
Journal: Circulation Research (1984)

The slow inward calcium currents were compared in rat and guinea pig heart using enzymatically dissociated, single ventricular cells. A single electrode voltage clamp was used, in which current and voltage were sampled separately using a time-sharing method. Spatial homogeneity of membrane potential during peak slow inward calcium current was assessed by measuring the potential with two microelectrodes 50 micron apart; the potentials were within 3 mV of each other. Peak current-voltage relations for slow inward calcium currents were similar for the two species, but the individual currents showed a faster time course of inactivation and a slower time course of recovery from inactivation for rat, compared with guinea pig. The potassium current blockers 4-aminopyridine and tetraethylammonium chloride did not produce significant effects on the net membrane currents recorded at the holding potentials (-50 to -40 mV) used in this study. The underlying mechanism for the inactivation of the slow inward calcium currents was explored using a double pulse procedure. In both rat and guinea pig heart cells prepulses to very positive potentials were associated with a partial restoration of the slow inward calcium current in the following test pulse. In addition, internal ethylene glycol-bis N,N,N',N'-tetraacetic acid or substitution of barium for calcium slowed the rate of inactivation of the slow inward calcium current in rat heart cells. Calcium activation of nonspecific currents was thought less likely to have produced these results due to the lack of effect of depolarizing prepulses on hyperpolarizing test pulses. A calcium-dependent component of inactivation may be responsible for the differences observed in both the inactivation and the recovery time courses of the slow inward calcium current in these species.
AN ELECTRON MICROSCOPIC STUDY OF INCOMPLETE VIRUS FORMATION
Authors: W. Robert Adams, Alfred M. Prince
Journal: The Journal of Experimental Medicine (1957)

The morphologic changes occurring in Ehrlich ascites tumor cells infected with chick embryo-adapted Newcastle disease virus were studied with phase microscope, conventional light microscope, and electron microscope. Intracytoplasmic inclusions appeared 2 to 4 hours following infection and progressively increased in size and numbers until cytolysis occurred. No significant alterations in mitochondria or other cell organelles were detected during the initial period of inclusion development. The inclusions were composed of a multilaminated shell, probably derived from the agranular reticulum of the EAT cell, surrounding an inner core packed with dense particles, measuring 3 to 14 mµ in diameter. These particles were tentatively identified as the newly synthesized "incomplete virus" which had been previously demonstrated by fluorescent antibody techniques. The possible role of the inclusions is discussed.
Lymphoid tissue phospholipase A2 group IID resolves contact hypersensitivity by driving antiinflammatory lipid mediators
Authors: Yoshimi Miki, Kei Yamamoto, Yoshitaka Taketomi, Hiroyasu Sato, Kanako Shimo, Tetsuyuki Kobayashi, Yukio Ishikawa, Toshiharu Ishii, Hiroki Nakanishi, Kazutaka Ikeda, Ryo Taguchi, Kenji Kabashima, Makoto Arita, Hiroyuki Arai, Gérard Lambeau, James M. Bollinger, Shuntaro Hara, Michael H. Gelb, Makoto Murakami
Journal: The Journal of Experimental Medicine (2013)

Resolution of inflammation is an active process that is mediated in part by antiinflammatory lipid mediators. Although phospholipase A2 (PLA2) enzymes have been implicated in the promotion of inflammation through mobilizing lipid mediators, the molecular entity of PLA2 subtypes acting upstream of antiinflammatory lipid mediators remains unknown. Herein, we show that secreted PLA2 group IID (PLA2G2D) is preferentially expressed in CD11c+ dendritic cells (DCs) and macrophages and displays a pro-resolving function. In hapten-induced contact dermatitis, resolution, not propagation, of inflammation was compromised in skin and LNs of PLA2G2D-deficient mice (Pla2g2d−/−), in which the immune balance was shifted toward a proinflammatory state over an antiinflammatory state. Bone marrow-derived DCs from Pla2g2d−/− mice were hyperactivated and elicited skin inflammation after intravenous transfer into mice. Lipidomics analysis revealed that PLA2G2D in the LNs contributed to mobilization of a pool of polyunsaturated fatty acids that could serve as precursors for antiinflammatory/pro-resolving lipid mediators such as resolvin D1 and 15-deoxy-Δ12,14-prostaglandin J2, which reduced Th1 cytokine production and surface MHC class II expression in LN cells or DCs. Altogether, our results highlight PLA2G2D as a “resolving sPLA2” that ameliorates inflammation through mobilizing pro-resolving lipid mediators and points to a potential use of this enzyme for treatment of inflammatory disorders.
Effect of radiotherapy and other treatment-related factors on mid-term to long-term cognitive sequelae in low-grade gliomas: a comparative study
Authors: M Klein, JJ Heimans, NK Aaronson, HM van der Ploeg, J Grit, M Muller, TJ Postma, JJ Mooij, RH Boerman, GN Beute, GJ Ossenkoppele, GW van Imhoff, AW Dekker, J Jolles, BJ Slotman, H Struikmans, MJB Taphoorn
Journal: The Lancet (2002)