tbuckley/cabot-search huggingface dataset:
Effects of acute systemic hyperinsulinemia on forearm muscle proteolysis in healthy man.
Authors: P Tessari, S Inchiostro, G Biolo, E Vincenti, L Sabadin
Journal: Journal of Clinical Investigation (1991)

To investigate the mechanism(s) of insulin-induced suppression of plasma amino acid concentration and release, we studied forearm as well as whole-body leucine and phenylalanine uptake and release during a peripheral insulin infusion in postabsorptive normal subjects using isotope-dilution methods. Before insulin, leucine and phenylalanine release exceeded uptake (P less than 0.01 and P less than 0.07, respectively). A net output of alpha-ketoisocaproate (KIC) was also observed. During insulin, arterial plasma leucine, KIC and phenylalanine concentrations decreased (P less than 0.05 or less vs. basal), despite ongoing net output of these substrates by the forearm, that persisted after correction for the mean transit time spent through the extracellular muscular space. By the end of insulin, whole-body leucine and phenylalanine concentrations and rate of appearance were decreased (P less than 0.01 vs. basal). However, release and uptake of both amino acids by the forearm were not significantly decreased vs. the preinsulin values. These data indicate that systemic hyperinsulinemia acutely decreases plasma amino acid concentrations by acting primarily at sites other than skeletal muscle.
Cooperation Not Confrontation: The Imperative of a Nuclear Age
Authors: Bernard Lown
Journal: JAMA (1985)

Reprinted here is the text of a speech to the Fifth Congress of the International Physicians for the Prevention of Nuclear War (IPPNW), delivered in Budapest on 29 June 1985 by the group's co-founders, Dr. Bernard Lown from the United States and Dr. Eugene Chazov from the U.S.S.R. After reminding the delegates that 1985 marked the 40th anniversary of the bombings of Hiroshima and Nagasaki and the founding of the United Nations, the two physicians review the work of the IPPNW in alerting the world to the dangers of nuclear warfare. They warn that the chances of nuclear confrontation have increased, and urge their colleagues to foster cooperation between East and West. Lown and Chazov identify nuclear war as the greatest public health threat of all, and call for a moratorium on all nuclear explosions.
Abstract 2022: P53-dependent thrombocytopenia induced by the histone deacetylase inhibitor S78454
Authors: Ashfaq Ali, Olivier Bluteau, Alberta Palazzo, Siham Boukour, Larissa Lordier, Philippe Rameau, Yann Leceluse, Laurence Kraus-Berthier, Anne Jacquet-Bescond, Hélène Lelièvre, Stéphane Depil, Eric Solary, Hana Raslova, William Vainchenker, Isabelle Plo, Najet DEBILI
Journal: Cancer Research (2012)

Abstract S78454 (also called PCI-24781) is an orally bioavailable, hydroxamate-based pan-HDACi currently being tested in clinical trials in the US and EU. Like many other HDACi, this drug induces a reversible thrombocytopenia. This thrombocytopenia, which was associated with a decrease in either GATA1 transcriptional activity or the expression of proteins of the Rho GTPase family (RhoA, Cdc42 or Rac), remains poorly understood. Given that the S78454 plasma level is above 100nM in treated patients, we performed a dose-response analysis (from 10 to 100 nM) of the drug effects on CFU-MK growth and cell proliferation. CFU-MKs were generated by ex vivo culture of CD34-positive cells and their differentiation was dose-dependently decreased after either a 24-hour treatment or a continuous exposure to S78454. This effect was associated with a dose-dependent decrease in MK proliferation. When added at day 8 of the culture, at a time-point when MK have nearly finished their endomitotic process and are entering in the cytoplasmic maturation step, S78454 induced a dose-dependent decrease (ten- to- two fold at 100nM and 20nM, respectively) in proplatelet formation, even when secondarily removed from the culture medium. The decreased proliferation was associated with an increased apoptosis, as demonstrated by the presence of a sub-G1 peak after propidium iodide staining, Annexin V binding, and caspase-3 proteolysis. We did not observed any blockade in the TPO/MPL/JAK2 signaling since ERK, Stat3 and Stat5 phosphorylation remained unaffected. Interestingly, MK exposed to S78454 displayed an increase in γH2AX foci formation and a decrease in Rad51 expression, a major mediator of homologous recombination, indicating a defective repair of DNA double-strand breaks. Consequently, P53 became phosphorylated in MKs, and the expression of its target genes BAX and P21 was increased. Altogether, these results suggest that S78454-induced thrombocytopenia may be mediated by induction of apoptosis in MK due to DNA-double-strand breaks and p53 activation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2022. doi:1538-7445.AM2012-2022
Peripheral Blood Signature of Vasodilator-Responsive Pulmonary Arterial Hypertension
Authors: Anna R. Hemnes, Aaron W. Trammell, Stephen L. Archer, Stuart Rich, Chang Yu, Hui Nian, Niki Penner, Mitchell Funke, Lisa Wheeler, Ivan M. Robbins, Eric D. Austin, John H. Newman, James West
Journal: Circulation (2014)

Background— Heterogeneity in response to treatment of pulmonary arterial hypertension (PAH) is a major challenge to improving outcome in this disease. Although vasodilator-responsive PAH (VR-PAH) accounts for a minority of cases, VR-PAH has a pronounced response to calcium channel blockers and better survival than vasodilator-nonresponsive PAH (VN-PAH). We hypothesized that VR-PAH has a different molecular cause from VN-PAH that can be detected in the peripheral blood. Methods and Results— Microarrays of cultured lymphocytes from VR-PAH and VN-PAH patients followed at Vanderbilt University were performed with quantitative polymerase chain reaction performed on peripheral blood for the 25 most different genes. We developed a decision tree to identify VR-PAH patients on the basis of the results with validation in a second VR-PAH cohort from the University of Chicago. We found broad differences in gene expression patterns on microarray analysis including cell-cell adhesion factors and cytoskeletal and rho-GTPase genes. Thirteen of 25 genes tested in whole blood were significantly different: EPDR1 , DSG2 , SCD5 , P2RY5 , MGAT5 , RHOQ , UCHL1 , ZNF652 , RALGPS2 , TPD52 , MKNL1 , RAPGEF2 , and PIAS1. Seven decision trees were built with the use of expression levels of 2 genes as the primary genes: DSG2 , a desmosomal cadherin involved in Wnt/β-catenin signaling, and RHOQ , which encodes a cytoskeletal protein involved in insulin-mediated signaling. These trees correctly identified 5 of 5 VR-PAH patients in the validation cohort. Conclusions— VR-PAH and VN-PAH can be differentiated with the use of RNA expression patterns in peripheral blood. These differences may reflect different molecular causes of the 2 PAH phenotypes. This biomarker methodology may identify PAH patients who have a favorable treatment response.
Tuberculosis in London in Wartime
Authors: W. A. Daley, B. Benjamin
Journal: BMJ (1942)

In order to assess the effect of war conditions upon the incidence of tuberculosis in Liondon, a review of the noti- fication rec'ords was undertaken.The results of such an analysis in respect of an urban area in which conditions immediately before the outbreak of hostilities were stable have helped to throw some light on the problem of con- trolling tuberculosis, and are recorded here in the hope that they will be of use to other workers in this field. Pulmonary TuberculosisThe general trend of pulmonary tuberculosis in London is indicated by Table I, which shows the numbers of formal primary notifications and the numbers of deaths since 1913, together with the corresponding rates.TABLE I.-Primary Notifications (a) of and Deaths from Pulmonary Tuber-culosis in the Administrative County of London
Mutated regions of nucleophosmin 1 elicit both CD4+ and CD8+ T-cell responses in patients with acute myeloid leukemia
Authors: Jochen Greiner, Yoko Ono, Susanne Hofmann, Anita Schmitt, Elmar Mehring, Marlies Götz, Philippe Guillaume, Konstanze Döhner, Joannis Mytilineos, Hartmut Döhner, Michael Schmitt
Journal: Blood (2012)
De Subitaneis Mortibus
Authors: THOMAS N. JAMES, DEREK J. L. CARSON, THOMAS K. MARSHALL
Journal: Circulation (1973)

Necropsy studies of sudden death should always include examination of the conduction system of the heart but seldom do. This case is an example of sudden unexpected death in which there was a fibroma compressing the His bundle. Almost by definition it will be necessary to reconstruct probable clinical events retrospectively in such cases and several such considerations are made here. By studying individual examples and appropriate groups of cases in this way, it should be possible to reduce the number of "unexplained" cases, to formulate reasonable hypotheses for prospective examination, and ultimately to devise means of preventing some of these deaths.
The renin-angiotensin system: it’s all in your head
Authors: Kelly K. Parsons, Thomas M. Coffman
Journal: Journal of Clinical Investigation (2007)

Components of the renin-angiotensin system (RAS) are expressed in a number of areas in the brain involved in cardiovascular control. However, it has been difficult to link RAS actions in circumscribed brain regions to specific physiological functions. In a study appearing in this issue of the JCI, Sakai and associates use a combination of sophisticated transgenic techniques and stereotaxic microinjection of recombinant viral vectors to demonstrate a pivotal role in the regulation of thirst and salt appetite of angiotensin II generated in the subfornical organ in the brain (see the related article beginning on page 1088).
Alpha Adrenergic Vasoconstriction and Nitroglycerin Vasodilation of Large Coronary Arteries in the Conscious Dog
Authors: Stephen F. Vatner, Massimo Pagani, W. Thomas Manders, Ares D. Pasipoularides
Journal: Journal of Clinical Investigation (1980)

The effects of methoxamine and nitroglycerin on measurements of large vessel (left circumflex) coronary dimensions were examined in eight conscious dogs using an ultrasonic dimension gauge, and total coronary resistance was calculated from measurements of arterial pressure and coronary blood flow. Methoxamine (50 μg/kg per min), after transiently increasing left circumflex coronary dimensions, induced sustained reductions in left circumflex diameter (9±2%) and external (18±4%) and internal (27±5%) cross-sectional areas, at a time when mean arterial pressure rose by 65±5%, left ventricular dP/dt had decreased only slightly, and heart rate and mean coronary blood flow remained at control levels. Calculated large vessel and total coronary resistances rose similarly, i.e., by 108±29 and 92±14%, respectively. Methoxamine reduced coronary arterial wall stiffness from control at comparable stress levels, although at any common radius, wall stiffness was augmented substantially. Nitroglycerin (25 μg/kg) induced an initial decrease in coronary dimensions along with the fall in arterial pressure. However, left circumflex coronary dimensions then rose, reaching a maximum 5 min later at a time when left circumflex coronary blood flow was reduced and heart rate and left ventricular dP/dt were at control levels. At this time, significantly different effects were observed on large vessel coronary resistance, which fell by 18±2%, and on total coronary resistance, which rose by 11±4%. Thus, in the conscious dog, large coronary vessels not only react passively to changes in aortic pressure but also undergo substantial active changes. Alpha adrenergic stimulation is sufficiently powerful to reduce cross-sectional area, despite the opposing elevation of distending pressure.
Hypersensitivity vasculitis due to ofloxacin.
Authors: D. Huminer, J. D. Cohen, R. Majadla, S. Dux
Journal: BMJ (1989)

Une observation - Malade de 67 ans diabetique, sous insuline depuis 15 ans, atteint d'une brulure du pied infectee. Le traitement par ofloxacine provoque une eruption purpurique prurigineuse, qui s'efface apres cessation du traitement et recidive apres reprise. Il s'agit d'une vasculite d'hypersensibilite, curable par prednisone
Treatment of prolactinomas with megavoltage radiotherapy.
Authors: A Grossman, B L Cohen, M Charlesworth, P N Plowman, L H Rees, J A Wass, A E Jones, G M Besser
Journal: BMJ (1984)

The outcome of treatment of 36 women with prolactinomas using megavoltage radiotherapy combined with interim dopamine agonists (bromocriptine, lysuride, pergolide) was reviewed; 16 of the women showed radiological evidence of a macroadenoma. The most common presenting symptom was secondary amenorrhoea; 26 of the patients had galactorrhoea. In 29 patients who wished to conceive the ovulation rate (as indicated by circulating progesterone concentrations) was 97% and the successful fertility rate 86%. No patient had enlargement of the tumour during pregnancy and there were no complications of radiotherapy. No further tumour enlargement was detected in serial skull radiographs, and an improvement in size of the fossa was noted in 45% of those assessed. When medical treatment was withdrawn a mean of 4.2 years (range 1-11) after radiotherapy in the 27 patients who had completed their families the serum prolactin concentration had fallen appreciably in 26 of them and later became normal in eight. The incidence of growth hormone deficiency rose from 24% of the whole group before radiotherapy to 79% afterwards. Only one patient required thyroxine, and one was receiving gonadotrophin. No patient became deficient in adrenocorticotrophic hormone. A regimen of megavoltage radiotherapy and interim bromocriptine allows women with prolactinomas safely to undergo pregnancy and results in the long term prospect of tumour shrinkage and control of hyperprolactinaemia.
Applications of metabolomics and proteomics to the mdx mouse model of Duchenne muscular dystrophy: lessons from downstream of the transcriptome
Authors: Julian L Griffin, Christine Des Rosiers
Journal: Genome Medicine (2009)

Functional genomic studies are dominated by transcriptomic approaches, in part reflecting the vast amount of information that can be obtained, the ability to amplify mRNA and the availability of commercially standardized functional genomic DNA microarrays and related techniques. This can be contrasted with proteomics, metabolomics and metabolic flux analysis (fluxomics), which have all been much slower in development, despite these techniques each providing a unique viewpoint of what is happening in the overall biological system. Here, we give an overview of developments in these fields 'downstream' of the transcriptome by considering the characterization of one particular, but widely used, mouse model of human disease. The mdx mouse is a model of Duchenne muscular dystrophy (DMD) and has been widely used to understand the progressive skeletal muscle wasting that accompanies DMD, and more recently the associated cardiomyopathy, as well as to unravel the roles of the other isoforms of dystrophin, such as those found in the brain. Studies using proteomics, metabolomics and fluxomics have characterized perturbations in calcium homeostasis in dystrophic skeletal muscle, provided an understanding of the role of dystrophin in skeletal muscle regeneration, and defined the changes in substrate energy metabolism in the working heart. More importantly, they all point to perturbations in proteins, metabolites and metabolic fluxes reflecting mitochondrial energetic alterations, even in the early stage of the dystrophic pathology. Philosophically, these studies also illustrate an important lesson relevant to both functional genomics and the mouse phenotyping in that the knowledge generated has advanced our understanding of cell biology and physiological organization as much as it has advanced our understanding of the disease.
Abstract 2024: Identification of novel oncogenes in a stage I small cell lung cancer through whole-genome sequencing.
Authors: Ji-Youn Han, Yeon Su Lee, Byung Chul Kim, Sung Hoon Lee, Geon Kook Lee, Youn-Sung Cho, Hak-Min Kim, Jin Soo Lee
Journal: Cancer Research (2013)

Abstract Background: Small cell lung cancer (SCLC) is rapidly progressive and most cases are presented with advanced stage. It hampers access to early stage cancer samples, which are essential to understand the early development of this disease. We performed whole-genome sequencing (WGS) of a stage I SCLC to analyze the genomic feature of early tumorigenesis of SCLC. Methods: We obtained normal and tumor genomic DNAs from a patient with stage I SCLC underwent curative resection and analyzed the normal and cancer genomes by WGS using 90 bp paired-end reads and validated the cancer variations by Sanger sequencing and single-nucleotide polymorphism (SNP) genotyping. Results: WGS revealed a lot of SNVs, small insertion/deletions, and chromosomal abnormality. Chromosomes 4p, 5q, 13q, 15q, 17p, and 22q contained many block deletions. Especially, copy loss was observed in tumor suppressor genes RB1 and TP53, and copy gain in oncogene hTERT. Recurrent somatic mutations were found in two genes, TP53 and CREBBP. Novel non-synonymous (ns) single nucleotide variations (SNV) were found in C6ORF103 and SLC5A4 genes. Sequencing of SLC5A4 gene in 23 independent limited disease SCLC samples revealed another ns SNV in SLC5A4 gene, indicating ns SNVs in SLC5A4 gene are recurrent in early -stage SCLC. This cancer genome had mutated genes associated with Notch and WNT signaling pathways. Conclusion: WGS analysis in this study provides the genomic landscape of early-stage SCLC, which may provide new insight into the early development of SCLC. Citation Format: Ji-Youn Han, Yeon Su Lee, Byung Chul Kim, Sung Hoon Lee, Geon Kook Lee, Youn-Sung Cho, Hak-Min Kim, Jin Soo Lee. Identification of novel oncogenes in a stage I small cell lung cancer through whole-genome sequencing. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2024. doi:10.1158/1538-7445.AM2013-2024
169 Angiotensin-converting enzyme I/D gene polymorphism and obesity following liver transplantation
Authors: P. Toniutto, R. Minisini, S. D'Alfonso, E. Fumo, F. Capelli, L. Apollonio, M. Caldato, R. Rapetti, S. Fangazio, M. Bulfone, A. Perin, M. Pirisi
Journal: Journal of Hepatology (2004)
Endoscopic Detection of Proximal Serrated Lesions and Pathologic Identification of Sessile Serrated Adenomas/Polyps Vary on the Basis of Center
Authors: Shannon R. Payne, Timothy R. Church, Michael Wandell, Thomas Rösch, Neal Osborn, Dale Snover, Robert W. Day, David F. Ransohoff, Douglas K. Rex
Journal: Clinical Gastroenterology and Hepatology (2013)
Three-Phase Bone Scanning in Chronic Myelogenous Leukemia
Authors: HAL N. GINSBERG, LAWRENCE C. SWAYNE
Journal: Clinical Nuclear Medicine (1987)

Although triple-phase bone scanning is sensitive in the diagnosis of acute osteomyelitis, several other etiologies (trauma, recent surgery, Paget's disease, primary bone tumors, and metastatic disease) have been reported to demonstrate increased activity in all three phases. An additional cause, leukemia, should be included in the differential diagnosis in the appropriate clinical setting.
Desert Storm Veterans Now May Donate Blood; Others Call for Discussion of Donor Tests
Authors: Phil Gunby
Journal: JAMA (1993)

PERSIAN GULF veterans are no longer banned from donating blood, as of this month. Fear that<i>Leishmania tropica</i>, a parasite transmitted by sand flea (<i>Phlebotomus papatasi</i>) bites, could be spread through transfusions prompted the November 12,1991, ban. Cutaneous leishmaniasis remained a concern during large-scale 1990 and 1991 US military operations in Saudi Arabia, Kuwait, and Iraq (<i>JAMA</i>. 1991;265:435,439-440) and now is listed by the US Army Medical Research and Development Command as a possible health threat to US troops in Somalia. <h3>No Transfusion Transmission</h3> However, "since there has been no documented case of transfusion-transmitted<i>L tropica</i>[during the nearly 14 months of the ban], and after a careful review of current information, American blood banks are being advised to drop the ban on blood donations from those individuals who were in the Persian Gulf during Operation Desert Shield/Storm," says Arthur J. Silvergleid, MD, president, American Association of Blood Banks. The
THE NERVES OF THE CAPILLARIES, WITH REMARKS ON NERVE-ENDINGS IN MUSCLE
Authors: Chr. Sihler
Journal: The Journal of Experimental Medicine (1901)

1. The endings of the motor nerves in striped muscle remain on the outside of the sarcolemma. Aside from the surfaces of contact of muscle and nerve fibre, the end fibres are covered down to their tips with the sheath of Schwann and are provided with nuclei. The precise condition of things at the places of contact of muscle and nerve is an unsolved problem of histology. 2. The ivy-like or festooned arrangement of motor nerves in the frog's muscle has been misinterpreted. Properly interpreted it demonstrates that the nerve fibres that are to influence the muscle fibre are not naked and that they need not be end fibres. It shows that mere contact between muscle fibre and nerve fibre is all that is necessary. 3. The sheath of Henle in the frog and in the smaller muscle fibres of the snake is open, thus permitting escape of the cerebrospinal fluid. 4. In other animals Henle's sheath extends over the end fibres of the motor nerve and the cells lining it envelop the end fibrils. I find that the so-called "Sohlensubstanz" of Kühne is derived from the cells of Henle's sheath. 5. The terminal nerves in smooth muscle form a network entwining the bundles of muscle fibres. I consider it improbable that each plain muscle fibre has a special terminal nerve fibril. 6. In muscular tissue fine non-medullated nerves, probably belonging to the centrifugal, vasomotor system, proceed from the fasciculi of motor nerves. These nerves can be traced directly to a network of nerves surrounding the capillaries. From this network fine, nucleated, nerve fibres pass to the walls of the capillaries, with which they are very closely united. 7. The nerves supplying the capillaries connect also with sensory nerves and with nerves surrounding the larger blood-vessels, both arteries and veins. 8. The branches of the chorda tympani in the submaxillary gland do not pass to the gland cells, but they terminate on the capillaries. 9. In muscular and glandular tissues-and perhaps throughout the body-there is a vast peripheral nervous plexus belonging to the capillary blood-vessels. These nerves of the capillaries, which may perhaps be regarded as nutritive nerves, regulate the production and transudation of lymph, and are concerned in the mechanism of glandular secretion. They may be called into activity both by peripheral influences and by impulses received from the central nervous system and the sympathetic ganglia. They may influence, through their connections with the vasomotor nerves on the arteries and veins, the blood supply to a part.