tbuckley/cabot-search huggingface dataset:
Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy
Authors: Ilona Hauber, Dorian Bevec, Jochen Heukeshoven, Friedrich Krätzer, Florian Horn, Axel Choidas, Thomas Harrer, Joachim Hauber
Journal: Journal of Clinical Investigation (2005)

The introduction of highly active antiretroviral therapy (HAART) has significantly decreased morbidity and mortality among patients infected with HIV-1. However, HIV-1 can acquire resistance against all currently available antiretroviral drugs targeting viral reverse transcriptase, protease, and gp41. Moreover, in a growing number of patients, the development of multidrug-resistant viruses compromises HAART efficacy and limits therapeutic options. Therefore, it is an ongoing task to develop new drugs and to identify new targets for antiretroviral therapy. Here, we identified the guanylhydrazone CNI-1493 as an efficient inhibitor of human deoxyhypusine synthase (DHS). By inhibiting DHS, this compound suppresses hypusine formation and, thereby, activation of eukaryotic initiation factor 5A (eIF-5A), a cellular cofactor of the HIV-1 Rev regulatory protein. We demonstrate that inhibition of DHS by CNI-1493 or RNA interference efficiently suppressed the retroviral replication cycle in cell culture and primary cells. We show that CNI-1493 inhibits replication of macrophage- and T cell-tropic laboratory strains, clinical isolates, and viral strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Moreover, no measurable drug-induced adverse effects on cell cycle transition, apoptosis, and general cytotoxicity were observed. Therefore, human DHS represents a novel and promising drug target for the development of advanced antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses.
Time-Resolved 3-Dimensional Magnetic Resonance Velocity Mapping at 3 T Reveals Drastic Changes in Flow Patterns in a Partially Thrombosed Aortic Arch
Authors: Alex Frydrychowicz, Ernst Weigang, Andreas Harloff, Friedhelm Beyersdorf, Jürgen Hennig, Mathias Langer, Michael Markl
Journal: Circulation (2006)
Radiology and Lumbar Disks
Authors: H. Davies
Journal: BMJ (1954)

<h3>Abstract</h3> Nine xylanolytic bacterial strains were isolated from fen and heath soils in northern Iceland. They were found by 16S rRNA gene sequencing to belong to the genera <i>Paenibacillus</i>, <i>Bacillus</i>, <i>Pseudomonas</i>, and <i>Stenotrophomonas</i>. Using a simple, plate-based semiquantitative assay with azo-crosslinked xylan as the substrate, it was determined that although isolated from cold environments, most of the strains displayed greater xylanolytic activity under mesophilic conditions, with only the paenibacilli displaying markedly cold-active xylanolytic activity. Indeed, for one isolate, <i>Paenibacillus castaneae</i> OV2122, xylanolytic activity was only detected at 15°C and below under the conditions tested. Of the nine strains, <i>Paenibacillus amylolyticus</i> OV2121 displayed the greatest activity at 5°C. Glycohydrolase family-specific PCR indicated that the paenibacilli produced multiple xylanases of families 10 and 11, whereas a family 8 xylanase was detected in <i>Pseudomonas kilonensis</i> AL1515, and a family 11 xylanase in <i>Stenotrophomonas rhizophila</i> AL1610.
Absence of hereditary p53 mutations in 10 familial leukemia pedigrees.
Authors: C A Felix, D D'Amico, T Mitsudomi, M M Nau, F P Li, J F Fraumeni, D E Cole, J McCalla, G H Reaman, J Whang-Peng
Journal: Journal of Clinical Investigation (1992)

Germline p53 mutations have been identified in the Li-Fraumeni syndrome but the role of such mutations in familial leukemia is not established. The p53 gene was examined by single-strand conformation polymorphism analysis of exons 4-8 in 10 families with multiple members affected with leukemia. The diagnoses included acute and chronic leukemias and Hodgkin's disease. Identified in two families were p53 mutations that were nonhereditary. These included a 2-bp deletion in exon 6 found in the lymphoblast DNA of one child whose sibling, cousin, and several adult relatives had acute leukemia. The other nonhereditary p53 mutation was a transition at codon 248 (CGG to CAG, arginine to glutamine) found in the lymphoblasts of a patient with a preleukemic syndrome and acute lymphoblastic leukemia (ALL) whose brother is a long-term survivor of ALL. Thus, p53 mutations were found to occur in two families but both were nonhereditary. Moreover, in the remaining eight families no p53 mutation was identified in the regions of p53 where most mutations have been found in other cancers. Although p53 mutations sometimes may be present, they do not appear to be a primary event responsible for hereditary susceptibility to familial leukemia. This study suggests involvement of other genes or mechanisms.
Assessment of cellular viability in cardiovascular tissue as studied with 3Hproline and 3Hinulin
Authors: J. Hu, L. Gilmer, R. Hopkins, L. Wolfinbarger
Journal: Cardiovascular Research (1990)

Study objective – The aim of the study was to develop a quantifiable assay for the assessment of cellular viability in cardiovascular tissue. Design – Radiolabelled proline and inulin were used to assess metabolic viability of the cellular component of cuspal tissue from porcine heart valves. Experimental materials – Pig hearts were removed within 20 min of death and transported on ice in tissue culture medium. Cuspal tissues were dissected rapidly and held on ice in physiological medium until assayed. Main results – Radiolabelled inulin was shown to be a useful marker for determining the amount of radiolabelled proline present in the extracellular tissue volume, permitting calculation of the amount of radiolabelled proline accumulated by the cellular component. Proline accumulation by the cellular component was affected by concentration of proline, time allowed for proline accumulation, in vitro cold ischaemia, and metabolic poisons. Based on mg tissue protein, proline and inulin accumulations were equivalent for aortic, pulmonary, mitral, and tricuspid valve tissues, suggesting that these valve tissues may be used interchangeably in assessment of metabolic viability of cellular components of cardiovascular tissue. Conclusion – Radiolabelled proline and inulin transport assays allow a quantitative estimate of total cellular viability.
Analysis of the binding surfaces of proteins
Authors: Dagmar Ringe, Carla Mattos
Journal: Medicinal Research Reviews (1999)

We have developed an experimental approach to map the complete binding surface of any crystalline macromolecule that is fast and flexible. Crystals of the target protein are transferred into organic solvents and the crystal structures are determined at high (about 2Å) resolution. The sites where the solvent molecules bind to the protein are thus identified directly. Different solvents serve as probes for different organic functional groups; thus, benzene is a probe for where aromatic groups like to bind, dimethyl formamide is a probe for peptide binding sites, and so forth. A series of about six such experiments suffices to locate the major binding regions on the protein surface unambiguously. These different sites can then be targeted with "Hydra-headed" inhibitors that interact simultaneously with more that one site, thereby providing specificity for the desired target. We have used this method to map the complete binding surface of elastase, and find that three regions, including the active site cleft, are generally "sticky" and can make interactions with almost any functional group. Analyses of these binding sites on elastase and other proteins suggests that what makes a binding site is amphipathicity and the ease with which water can be displaced. © 1999 John Wiley & Sons, Inc. Med Res Rev, 19, No. 4, 321–331, 1999.
ANATOMY OF THE INGUINAL REGION.
Authors: T. CASEY WITHERSPOON
Journal: JAMA (1906)

This paper is limited to the region of the inguinal canal and enters into a description of such portions of the various structures as are directly included in this territory. The observations are based on some fifty dissections. They have been compared with the descriptions in Toldt, Spalteholz, Morris, Gray, Deaver and Zukerkandel and found to be somewhat at variance with them. These textbooks were selected as representative of the anatomies usually referred to. A few monographs on the subject have been consulted with the same results. It would carry the paper to too great lengths to discuss these differences in connection with the findings here presented. This lack of uniformity of description has led to the publication of the present paper, in which are included such original drawings as are necessary to illustrate the text. The old nomenclature has been adhered to, although the terms often convey false ideas
Perioperative Parenteral Nutrition: A Meta-Analysis
Authors: ALLAN S. DETSKY
Journal: Annals of Internal Medicine (1987)

We used a meta-analysis protocol to evaluate the results of 18 controlled trials that measured the effectiveness of perioperative total parenteral nutrition. The pooled results of 11 trials that were randomized or quasi-randomized showed trends suggesting that total parenteral nutrition reduced the risk for complications from major surgery (p = 0.21) and fatalities (p = 0.21). Consideration of these pooled estimates of the effectiveness of this intervention must be offset by the poor quality of the trials' methodologies and the iatrogenic complications (pneumothorax, septicemia) that occurred at a pooled rate of 0.067. Alternately, other design flaws, such as the failure to exclude patients who were not malnourished from the trials, may have limited the ability of these trials to show the effectiveness of total parenteral nutrition. The evidence available up to August 1986 shows that the routine use of perioperative total parenteral nutrition in unselected patients having major surgery is not justified; however, this intervention may be helpful in subgroups of these patients who are at high risk.
Contribution of Vasodilator Prostanoids and Nitric Oxide to Resting Flow, Metabolic Vasodilation, and Flow-Mediated Dilation in Human Coronary Circulation
Authors: Stephen J. Duffy, Sally F. Castle, Richard W. Harper, Ian T. Meredith
Journal: Circulation (1999)

Background —Endothelial dysfunction is associated with atherosclerosis and may contribute to ischemic syndromes. We assessed the contribution of endothelium-derived nitric oxide (NO) and vasodilator prostanoids to resting blood flow, metabolic vasodilation, and flow reserve in the human coronary circulation. Methods and Results —Coronary hemodynamics were assessed before and after inhibition of vasodilator prostanoids and NO with intracoronary aspirin (acetylsalicylic acid [ASA]) and N G -monomethyl- l -arginine (L-NMMA), respectively. Angiographically smooth or mildly irregular vessels, with normal adenosine-induced coronary flow reserve, were studied in 25 patients undergoing clinically indicated procedures. Coronary blood velocity was measured by Doppler flow wire, and coronary blood flow (CBF) was calculated. ASA reduced resting conduit vessel diameter by 11% ( P =0.003) and CBF by 27% ( P =0.008) and increased coronary vascular resistance (CVR) by 24% ( P &lt;0.0001). ASA attenuated pacing-induced hyperemia by 28% (45.0±4.6 versus 32.6±3.4 mL/min, P =0.005) and increased minimum CVR by 39% (2.8±0.3 versus 3.9±0.5 mm Hg · mL −1 · min −1 , P =0.007). L-NMMA reduced resting conduit vessel diameter by 9% ( P =0.05) and CBF by 20% ( P =0.08) and increased CVR by 19% ( P =0.03). L-NMMA attenuated pacing-induced hyperemia by 20% (42.4±5.1 versus 34.1±3.4 mL/min, P =0.04) and increased minimum CVR by 33% (2.9±0.4 versus 3.8±0.5 mm Hg · mL −1 · min −1 , P =0.02). ASA (7.7±2.3% versus −1.6±3.2%, P =0.06) and L-NMMA (12.1±3.9% versus 0.0±2.9%, P =0.02) abolished pacing-induced conduit vessel flow–mediated dilation. Conclusions —Tonic release of vasodilator prostanoids and NO contributes to resting conduit and resistance vessel tone and to peak functional hyperemia and flow-mediated dilation after metabolic stimulation. This underscores the importance of normal endothelial function for metabolic vasodilation and suggests that it may be a key mechanism for preventing myocardial ischemia in coronary artery disease.
Proposed Nomenclature and Classification of the Dye-spraying Techniques in Endoscopy
Authors: K. Kawai, T. Takemoto, S. Suzuki, K. Ida
Journal: Endoscopy (1979)

In this short communication, we propose a new nomenclature and classification of dye-spraying techniques in digestive endoscopy. The procedures with dyestuffs which had been reported in diagnostic endoscopy were divided according to actions of the dyesolutions into three methods; ie. Contrast, Biological Staining and Chemical Reaction methods. Recent application of fluorescent dyes to the diagnostic field were also added to the list as the fourth technique. The term “Contrast method” should be applied to a technique for enhancing the relief on the mucosal surface. Indigo Carmine and Evans Blue were available for this method. The second term, “Biological Staining", concerns an effect of vital staining where a dye applied on the mucosa was absorbed through the cellular membrane and stored in the cytoplasm. Several basic dyestuffs, Janus Green B, Neutral Red and Methylene Blue, are usually called “in vivo” staining dyes. When a dye on the mucosal surface reacted with a constituent of the epithelial cell, or with secretion at an adequate pH level, we use the term “Chemical Reaction” method. In this technique, Lugol's solution was applied to the esophageal epithelium and Congo Red to the gastric mucosa. In the practice of dye-spraying in diagnostic endoscopy, a suitable protocol is recommended for recording the instrumentation, medication, dye effect and complications. Complications have never been reported, but any possible long-term biological effect of the dyes had to be closely watched when the examination was repeated.
A State Plans for Its Future in Medical Education
Authors: John D. Porterfield
Journal: JAMA (1965)

There are so many dimensions to be considered in medical education and in its future form, substance, and balance that it would be difficult merely to enumerate them in the limits of a single presentation. It would also be in great part redundant in the context of the program of the 61st Annual Congress on Medical Education, for older heads and wiser have expounded before and will again on the dynamic character of medical education. Suffice it to say, in preface, that we are not at the crossroads, a favorite cliché of those viewing the contemporary scene. Rather we are, and happily so, in a relatively continuous state of flux as we attempt to remain contemporary in the face of shifting needs, growing volume of knowledge, improvement in teaching methodology, and the everplaguing increase in costs. In this presentation I should like to concentrate for the most part on the
RE-EVALUATION OF ANCILLARY THERAPIES
Authors: L. C. HARTLAGE
Journal: American Journal of Psychiatry (1964)

The majority of the problems enumerated, although typically chronic, are, for the most part, neither too serious nor too inevitable, provided periodic evaluations of the programs are made in terms of what they currently contribute to the total treatment process rather than existing as programs for programs' sake. Most of these were conceived in a spirit of humanity and the Christian ethic, in an attempt to ameliorate the situation of the patient sentenced to custodial incarceration, and were no doubt quite useful in that function. The fact that some of their practices and orientations have become obsolete is not so much an indictment of the proponents of these programs as a tribute to the progress made in the general field of mental health since the early part of the present century. What is needed is not so much a house cleaning as a rearrangement, with proportionate allocations made to those activities contributing most to the ultimate goals of the hospital in keeping with current philosophies.
Sense and Nonsense of Influenza Vaccination in Asthma and Chronic Obstructive Pulmonary Disease
Authors: Philip H. Rothbarth, Brigitte M. Kempen, Marc J. W. Sprenger
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Although influenza is generally seen as an important cause of excess mortality in patients with asthma or chronic obstructive pulmonary disease (COPD), this mortality is nearly exclusively present in patients over the age of 60. Morbidity in patients with asthma or COPD is related to respiratory infections, including influenza. Vaccination against influenza has proven to be effective in nursing home populations, decreasing both mortality and morbidity during epidemics of influenza A. In younger patients with asthma or COPD, however, the effect of vaccination is more ambiguous. Exacerbation of respiratory disease is not due to influenza vaccination (except in allergy to chicken protein), from which we can conclude that influenza vaccination is a safe method to prevent a potentially serious respiratory infection in patients with asthma or COPD.
Research related to surgical treatment of aortic and peripheral vascular disease.
Authors: M E DeBakey
Journal: Circulation (1979)

The history of vascular surgery and the developments that made it possible are briefly traced. Approaches to the treatment of arterial lesions are considered in terms of the characteristic anatomic, pathologic and clinical patterns of arteriosclerosis or atherosclerosis, the basic underlying lesion in most aneurysmal and occlusive diseases of the aorta and major arteries. The importance of appreciating the various patterns and rates of progression of atherosclerosis is emphasized.
PATIENTS ADMITTED WITH ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION AND A NORMAL OR NEAR NORMAL CORONARY ANGIOGRAM HAVE A FAVORABLE PROGNOSIS: ANALYSIS FROM HORIZONS-AMI TRIAL
Authors: Alf-Ing Larsen, Dennis WT Nilsen, Eugenia Nikolsky, Alexandra J. Lansky, Adriano Caixeta, Helen Parise, Martin Fahy, Ecaterina Criatea, Bernhard Witzenbichler, Giulio Guagliumi, Jan Z. Peruga, Bruce R. Brodie, Dariusz Dudek, Roxana Mehran, Gregg W. Stone
Journal: Journal of the American College of Cardiology (2010)
Ga-67 Citrate and Tc-99m Pertechnetate Scintigraphy in Thyroid Lymphoma
Authors: Parul Bhatnagar, Maheshwar Sahu, Mukta Jain, Harish Rawat, Aseem Bhatnagar, Ravi Kashyap
Journal: Clinical Nuclear Medicine (2004)

Primary thyroid lymphoma is an extremely rare malignancy. Only a few case reports of scintigraphy of lymphoma of the thyroid with Ga-67 citrate have been described in the English literature. The authors report a case of non-Hodgkin lymphoma that presented with a solitary nodule in the thyroid and in which Ga-67 scintigraphy was useful in the diagnosis of the thyroid lymphoma.
Association of Cerebral Emboli With Accelerated Cognitive Deterioration in Alzheimer's Disease and Vascular Dementia
Authors: Nitin Purandare, Alistair Burns, Julie Morris, Ewan P. Perry, Joanne Wren, Charles McCollum
Journal: American Journal of Psychiatry (2011)

Transcranial Doppler imaging found middle cerebral artery emboli in nearly half of patients with either vascular or Alzheimer's dementia. Patients with emboli had more rapid progression of dementia over 2 years than those who were emboli free, and their declines in overall functioning and behavior were over two times as great.
Urokinase receptor is a key player in tumour progression
Authors: T TANIGUCHI, N R LEMOINE, A K KAKKAR
Journal: Gut (1998)

See article on page 798 

Cell–cell and cell–extracellular matrix (ECM) interactions are essential for cell migration, tissue remodelling, angiogenesis, and tumorigenesis. Pericellular proteolysis of cell surface molecules and ECM provides crucial information in the local environment. Urokinase (uPA) plays an important role through the activation of plasminogen to plasmin, which regulates degradation of elements within the ECM, such as fibrin, fibronectin and lamin, and proteolytic activation of growth factors including hepatocyte growth factor (HGF), basic fibroblast growth factor (FGF-2) and transforming growth factor β (TGF-β). Plasmin also activates the proenzyme forms of the matrix metalloproteinases (MMPs), such as MT1-MMP,1MMP-2 and MMP-9.2 uPA activation is regulated by its specific cell surface receptor, urokinase receptor (uPAR). Binding of uPA to its receptor (uPAR) accelerates uPA activation from an inactive proenzyme (pro-uPA). The activity of plasminogen activators can be regulated by the specific inhibitors, plasminogen activator inhibitor 1 (PAI-1) and plasminogen activator inhibitor 2 (PAI-2). The urokinase system is implicated in tumour cell invasion on a basis of generally increased uPA activity in metastatic tumours. In particular, uPAR expression on the surface …
NHS pay rises must lead to better services, say MPs
Authors: Jeremy Davies
Journal: BMJ (2004)

The Department of Health must ensure that the extra money it is spending on doctors' and other health professionals' pay is matched by productivity gains, a cross party committee of MPs warned this week.

The House of Commons Public Accounts Committee made its comments in a progress report on the three year, £61bn ($110bn; €88bn) package of increased public spending announced by the chancellor of the exchequer, Gordon Brown, in July 2002. In the report MPs emphasised that the government departments that received the biggest funding increases—the Department of Health, the Department for Education and Skills, and the Department of Transport—must assure themselves that spending on higher …
Salmonella gastroenteritis—another cause of erythema nodosum
Authors: BRIAN B. SCOTT
Journal: British Journal of Dermatology (1980)

Although there are many causes and associations of erythema nodosum, it remains a useful sign often giving a clue to the diagnosis of a puzzling illness. It is therefore important for clinicians to be aware of all the possible causes and associations. The following report is of a patient in whom typical erythema nodosum developed during the course of severe salmonella gastroenteritis.
Neuropathy Associated with Hepatitis in Patients Maintained on Haemodialysis
Authors: A. M. Davison, I. R. Williams, C. Mawdsley, J. S. Robson
Journal: BMJ (1972)

During a study of peripheral nerve function in chronic renal failure, 11 patients who were being treated by chronic intermittent haemodialysis developed serum hepatitis. Before the infection there was a trend towards improvement in nerve conduction velocities. A pronounced deterioration in the conduction velocities in motor fibres of peripheral nerves occurred in association with hepatitis. In the months after recovery from the infection there was again a trend towards improvement in conduction velocities. We suggest that this reflects the occurrence of a peripheral neuropathy which is at least in part demyelinating. The neuropathy is related to the serum hepatitis, but its pathogenesis is indeterminate.
Regulation of hepatic apolipoprotein B RNA editing in the genetically obese Zucker rat
Authors: T.L. Phung, M.P. Sowden, J.D. Sparks, C.E. Sparks, H.C. Smith
Journal: Metabolism (1996)

Hepatic apolipoprotein (apo) B RNA editing was examined in the genetically obese hyperinsulinemic and hypertriglyceridemic Zucker rat.In obese Zucker rats, apo B RNA editing was increased 42% relative to that in lean controls.Correspondingly, the proportion of serum triglyceride-rich lipoprotein containing apo B48 increased 4.7-fold in the obese Zucker rat.Quantification of hepatic total apo B mRNA showed no difference between obese Zucker and lean control rats.In contrast, the hepatic mRNA encoding APOBEC-1, the catalytic subunit of the RNA editing activity, demonstrated an increased abundance of 1.8-fold in obese Zucker rats versus lean controls.