tbuckley/cabot-search huggingface dataset:
Identification and Genomic Analysis of Transcription Factors in Archaeal Genomes Exemplifies Their Functional Architecture and Evolutionary Origin
Authors: E. Perez-Rueda, S. C. Janga
Journal: Molecular Biology and Evolution (2010)

Archaea, which represent a large fraction of the phylogenetic diversity of organisms, are prokaryotes with eukaryote-like basal transcriptional machinery. This organization makes the study of their DNA-binding transcription factors (TFs) and their transcriptional regulatory networks particularly interesting. In addition, there are limited experimental data regarding their TFs. In this work, 3,918 TFs were identified and exhaustively analyzed in 52 archaeal genomes. TFs represented less than 5% of the gene products in all the studied species comparable with the number of TFs identified in parasites or intracellular pathogenic bacteria, suggesting a deficit in this class of proteins. A total of 75 families were identified, of which HTH_3, AsnC, TrmB, and ArsR families were universally and abundantly identified in all the archaeal genomes. We found that archaeal TFs are significantly small compared with other protein-coding genes in archaea as well as bacterial TFs, suggesting that a large fraction of these small-sized TFs could supply the probable deficit of TFs in archaea, by possibly forming different combinations of monomers similar to that observed in eukaryotic transcriptional machinery. Our results show that although the DNA-binding domains of archaeal TFs are similar to bacteria, there is an underrepresentation of ligand-binding domains in smaller TFs, which suggests that protein–protein interactions may act as mediators of regulatory feedback, indicating a chimera of bacterial and eukaryotic TFs' functionality. The analysis presented here contributes to the understanding of the details of transcriptional apparatus in archaea and provides a framework for the analysis of regulatory networks in these organisms.
Prospective study on the effect of smoking and nicotine substitution on leucocyte blood counts and relation between blood leucocytes and lung function
Authors: E. J. Jensen, B. Pedersen, R. Frederiksen, R. Dahl
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The influence of smoking and of nicotine substitution on the counts of total blood leucocytes and leucocyte subsets and the relations between the counts and lung function was investigated. <h3>METHODS</h3> The study was a combined cross sectional and prospective study of 298 smokers and 136 non-smokers. Forced expiratory volume in one second (FEV<sub>1</sub>) was measured in all participants at baseline and six months after quitting smoking in 160 ex-smokers (quitters) and 138 persons with smoking relapse. Blood samples were obtained from all participants at baseline and from 160 quitters and 30 continuing smokers two, six, 12, and 26 weeks after smoking cessation and from 92 quitters one year after the cessation of smoking. <h3>RESULTS</h3> Blood leucocyte counts and leucocyte subsets were all higher in smokers than in non-smokers. In cigarette smokers total leucocyte, neutrophil, and lymphocyte blood counts showed a dose dependent relationship with the daily cigarette consumption and pack years consumption. In smokers the neutrophil blood count was independently associated negatively with FEV<sub>1</sub> residuals. After quitting smoking total leucocyte, neutrophil, and lymphocyte blood counts decreased during the first 26 weeks and after one year lymphocyte blood counts were higher than in non-smokers. In quitters substituted with nicotine chewing gum (2 mg) the accumulated number of pieces of chewing gum used in the 12 weeks had an inverse relationship with the decrease in the total lymphocyte blood count at 12 weeks after smoking cessation. <h3>CONCLUSIONS</h3> Leucocyte blood counts are raised in smokers and decrease after smoking cessation. Neutrophil blood counts had an inverse relationship with lung function and nicotine may increase lymphocyte blood counts in smokers.
Levodopa: long-term impact on Parkinson's disease.
Authors: G O Tippett
Journal: BMJ (1981)

<h3>Abstract</h3> Spliceosomal introns are ubiquitous non-coding RNAs typically destined for rapid debranching and degradation. Here, we describe 34 excised <i>Saccharomyces cerevisiae</i> introns that, although rapidly degraded in log-phase growth, accumulate as linear RNAs under either saturated-growth conditions or other stresses that cause prolonged inhibition of TORC1, a key integrator of growth signaling. Introns that become stabilized remain associated with components of the spliceosome and differ from the other spliceosomal introns in having a short distance between their lariat branch point and 3′ splice site, which is necessary and sufficient for their stabilization. Deletion of these unusual introns is disadvantageous in saturated conditions and causes aberrantly high growth rates of yeast chronically challenged with the TORC1 inhibitor rapamycin. Reintroduction of native or engineered stable introns suppresses this aberrant rapamycin response. Thus, excised introns function within the TOR growth-signaling network of <i>S. cerevisiae</i>, and more generally, excised spliceosomal introns can have biological functions.
Risk factors for new-onset cat sensitization among adults: A population-based international cohort study
Authors: Mario Olivieri, Jan-Paul Zock, Simone Accordini, Joachim Heinrich, Deborah Jarvis, Nino Künzli, Josep M. Antó, Dan Norbäck, Cecilie Svanes, Giuseppe Verlato
Journal: Journal of Allergy and Clinical Immunology (2011)
Managing conjunctivitis in general practice: Research into management strategies for acute infective conjunctivitis
Authors: S. J Robbie
Journal: BMJ (2006)

I just wanted to be a doctorWe need to be more than "just" doctors Editor-Hunt articulates the feelings of many doctors on discovering that the effective practice of modern medicine requires a range of skills beyond the provision of direct clinical care. 1 Her slightly delayed entry into medicine may explain why this issue is troubling her now, rather than later in her career: certainly these are sentiments I hear more commonly from consultant colleagues than juniors.However, to imagine that good medical practice is confined to the delivery of care to one patient at a time is to overlook the role of doctors in organising healthcare systems and delivery in the wider context.It is disappointing that Hunt's appraiser chose to frame the process in terms of her trust's participation in the clinical negligence scheme, since most junior doctors value well conducted appraisals.Nevertheless, cheaper insurance premiums for hospitals mean more money to spend on health care, and also indicate that organisations that carry out effective appraisal make fewer clinical errors: presumably these are both outcomes that Hunt would approve of.Furthermore, research and audit without the active participation of doctors will soon become clinically irrelevant or ineffective.We have a wider responsibility for patient care that is served by informed participation in these and many other activities, such as teaching and continuous quality improvement (which also seem to get irritatingly in the way of a narrowly focused approach to patient care).However, all is not lost.Hunt appears well placed to fall into the "Modernising Medical Careers" vacuum that currently threatens to swallow those junior doctors who are too old for a foundation programme yet too young to have secured a specialist registrar post.If this does indeed curtail all opportunities for career progression she may end up as "just" a doctor after all.
811 RESPONSE TO TREATMENT FOLLOWING RECENTLY ACQUIRED HEPATITIS C VIRUS INFECTION
Authors: J.S. Doyle, K. Deterding, J. Grebely, H. Wedemeyer, R. Sacks- Davis, G. Matthews, T. Rice, M. Morris, B.H. McGovern, A.Y. Kim, J. Bruneau, A.R. Lloyd, K. Page, M. Manns, M.E. Hellard, G.J. Dore
Journal: Journal of Hepatology (2013)
Metastatic Melanoma Detected by Tc-99m Sestamibi During Routine Cardiac Imaging
Authors: VINCE A. PARTAP, MARC HICKESON, URVI JOSHI
Journal: Clinical Nuclear Medicine (1999)

A 65-year-old man underwent routine stress Tc-99m sestamibi imaging for typical chest pain. Standard treadmill exercise with the Bruce protocol was performed and 30 mCi Tc-99m sestamibi was injected when the target heart rate was attained. Tomographic and planar images of the thorax obtained 1 hour later showed no significant cardiac perfusion abnormality, but multiple areas of increased tracer uptake were apparent in the anterior chest wall. Clinical evaluation revealed palpable masses in the anterior chest wall, and biopsy proved these to be metastatic melanoma.
Evaluation of a Tumor Microenvironment–Based Prognostic Score in Primary Operable Colorectal Cancer
Authors: James H. Park, Donald C. McMillan, Arfon G. Powell, Colin H. Richards, Paul G. Horgan, Joanne Edwards, Campbell S.D. Roxburgh
Journal: Clinical Cancer Research (2014)

Abstract Purpose: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment–based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. Experimental Design: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup–Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I–III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. Results: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36–2.73; P &amp;lt; 0.001), independent of TNM stage and venous invasion (both P &amp;lt; 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P &amp;lt; 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). Conclusions: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer. Clin Cancer Res; 21(4); 882–8. ©2014 AACR.
Estrogen replacement therapy in breast cancer survivors
Authors: R. Vassilopoulou-Sellin
Journal: JAMA (1995)

To the Editor.  —We wholeheartedly applaud the suggestion by Dr Cobleigh and colleagues1that the role of ERT in the care of postmenopausal women with a history of breast cancer should be defined in a thoughtful and broad-minded manner through carefully designed prospective clinical trials. The realization that omission of the ERT option may no longer be appropriate for all women previously treated for breast cancer has led us to initiate such a prospective study, as the authors point out.2During our interactions with postmenopausal women with prior diagnosis of breast cancer, both within our institution3and in the community, we are impressed by their compelling descriptions of the deleterious effects of estrogen deficiency on their sense of well-being. The principle that no one medical intervention is ever appropriate for all individuals appears intuitively obvious but merits repetition. We would like to caution that neither ERT nor
Infection with polyomavirus JC
Authors: M. Lazrek
Journal: BMJ (2011)

Because there is a paucity of information on the perioperative risk of developing complete heart block among patients with bifascicular block (either right bundle branch block and left anterior hemiblock or left bundle branch block) and a long PR interval on the surface electrocardiogram, we undertook an analysis of 76 such patients. Twenty-three patients had right bundle branch block and left axis deviation with a long PR interval and 53 had left bundle branch block with along PR interval. Thirty patients had 37 general anaesthetics, 23 had 32 spinal anaesthetics, and 50 had 64 local anaesthetics or endoscopic procedures. No patient developed complete heart block. Four patients developed sinus bradycardia during general anaesthetics, responsive to atropine or isoproterenol. Similarly, none of the 23 such patients in the literature reviewed had developed complete heart block. Because placement to temporary pacemakers is not without risk, we conclude that prophylactic pacing is not necessary in asymptomatic patients with bifascicular block even in the presence of a long PR interval. Since we did not study patients with recent syncope or myocardial infarction, caution should be exercised in applying these results to such patients.
A Human Case of Skunk Rabies
Authors: Manuel R. Gomez
Journal: JAMA (1965)

A patient acquired rabies from the bite of skunk, despite prophylactic treatment with duck-embryo vaccine. Although rabies virus was not recovered from the patient's saliva and Negri bodies were not found in his brain, rabies developed in infant mice intracranially inoculated with brain homogenate. This is the first case of human rabies in Minnesota since 1917.
THE GROWTH OF LYMPHOSARCOMA IN DOGS.SUMMARY OF RECENT OBSERVATIONS.
Authors: S. P. BEEBE
Journal: JAMA (1907)

During the last two years the Huntington Cancer Research Fund has been, in part, devoted to the study of a tumor which occurs naturally in dogs. This tumor, under the name of "infectious lymphosarcoma," has been the subject of investigation and observation at other laboratories during recent years, and because of its ease of transplantation it affords a splendid opportunity to study experimentally the tumor process in a large animal. Nearly all the opinions in regard to the nature of the growth support the belief that it is a neoplasm, and the term infectious has been applied to it, because the tumor occurs naturally on the genital organs and may be transmitted by coitus. The process has been called by a few pathologists, notably Bashford, an infectious granuloma, comparable in many respects to syphilis. Very early in our study of the growth we realized the necessity of having additional information
HIV in Semen-Reply
Authors: Deborah J. Anderson
Journal: JAMA (1992)

In Reply.  —The letter by Dr Kiessling highlights concerns that we had expressed in our recent report on HIV in semen published in JAMA and also the need for the standardization and optimization of methods for detection of HIV in semen. We attributed the low overall culture rate in our recent study to the increased use of zidovudine and higher percentage of asymptomatic men in this study. Our data suggest that both of those factors (zidovudine therapy, early disease stage) are associated with lower levels of HIV in semen. Indeed, our HIV culture rate was less than 50% for men in advanced disease stage not receiving zidovudine therapy. In a recent workshop, standardized HIV stock was distributed to various laboratories for comparison of the sensitivity of semen culture method (described below). The HIV microculture technique used in our report detected 1 TCID 50 (tissue culture infectious dose) of cell-free and
The Impact of Streptozotocin-induced Diabetes Mellitus on Cyclic Nucleotide Regulation of Skeletal Muscle Amino Acid Metabolism in the Rat
Authors: Alan J. Garber
Journal: Journal of Clinical Investigation (1980)

The impact of diabetes on cyclic nucleotide-associated mechanisms regulating skeletal muscle protein and amino acid metabolism was assessed using epitrochlaris preparations from streptozotocin-induced diabetic rats. 1 nM epinephrine inhibited alanine and glutamine release from control preparations, but no inhibition was observed from diabetic preparations with <0.1 mM. 10 nM epinephrine stimulated lactate production from control muscle but stimulation in diabetic preparations was observed only at 0.1 mM. Serotonin inhibited amino acid release and stimulated lactate production equally in control and diabetic muscle. 0.1 mM epinephrine increased cyclic (c)AMP levels by 360% in control muscles, but these levels were increased only 83% in diabetic muscle. Basal-, fluoride-, and serotonin-stimulated adenylyl cyclase activities were equal in membrane preparations of diabetic and control muscle, but epinephrine-stimulated adenylyl cyclase was reduced by 60% in diabetic muscle. Carbamylcholine stimulation of alanine and glutamine release was blunted in diabetic preparations. Carbamylcholine increased cGMP levels in control but not in diabetic muscle. In diabetic muscle, guanylyl cyclase activity was 65% of control and the stimulation of cyclase activity by sodium azide was less in diabetic than control preparations. Added cGMP stimulated alanine and glutamine release from control, but not from diabetic muscle. These data suggest a loss of adrenergic and cholinergic responsiveness in diabetic muscle. Because amino acid release also showed a decreased responsiveness to added cAMP and cGMP, the presence of other derangements in the mechanism(s) of cyclic nucleotide regulation of muscle amino acid metabolism also seems likely.
In the Valley of the Kings
Authors: Tony Miksanek
Journal: JAMA (2010)

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Is Early Bladder Activity in Radionuclide Cisternography an Indirect Sign of Spontaneous Intracranial Hypotension or Sequence of Lumbar Puncture?
Authors: Metin Halaç, Sait Albayram, Elvan Ceyhan, Harun Ozer, Ismail Doǧan, Sait Sager, Ilhami Uslu
Journal: Clinical Nuclear Medicine (2007)

Spontaneous intracranial hypotension (SIH) is characterized by severe postural headache and low cerebrospinal fluid (CSF) pressure. Radionuclide cisternography (RC) is of some value in diagnosing CSF leakage causing SIH. However, the sensitivity of RC is too low to demonstrate the site of leakage. In these cases, the early appearance of the radioactivity in the urinary bladder has also been used as an indirect finding in the diagnosis of SIH. The aim of this study was to evaluate the diagnostic reliability of early urinary bladder activity as an indirect sign of SIH. We investigated early bladder activity in 21 patients with suspicion of normal pressure hydrocephalus. Of the 21 subjects, 13 (62%) showed early bladder activity. We demonstrated that early bladder activity is observed in patients without CSF leakage such as normal pressure hydrocephalus. Therefore, this indirect finding of RC is not a reliable finding in diagnosing SIH.
Systemic involvement of acute generalized exanthematous pustulosis: a retrospective study on 58 patients
Authors: C. Hotz, L. Valeyrie-Allanore, C. Haddad, S. Bouvresse, N. Ortonne, T.A. Duong, S. Ingen-Housz-Oro, J.C. Roujeau, P. Wolkenstein, O. Chosidow
Journal: British Journal of Dermatology (2013)

Acute generalized exanthematous pustulosis (AGEP) is a severe cutaneous adverse reaction characterized by rash with sterile pustules, high fever and elevated circulating neutrophil counts.To investigate the frequency and clinical features of AGEP systemic involvement.This retrospective study included all patients hospitalized in our department between 2000 and 2010 with a discharge diagnosis of AGEP. Patients had to fulfil the following criteria: (i) a specific EuroSCAR score > 4 and (ii) biological and radiological work-up available.Among the 58 patients enrolled, 10 had at least one systemic involvement: hepatic function test results were abnormal for seven; six had renal insufficiency; two developed acute respiratory distress, with one patient's bronchoalveolar lavage fluid containing many neutrophils but no microorganisms; one was agranulocytotic. Mean peripheral neutrophil counts and mean C-reactive protein levels were elevated significantly in patients with systemic involvement. Amoxicillin rechallenge and hospitalization duration were associated with systemic involvement. AGEP systemic involvement was observed in 17% of cases studied, including liver, kidney, bone-marrow and lung involvement. Outcomes were favourable after drug withdrawal, and symptomatic and topical steroid treatments.The neutrophil count-systemic involvement association may suggest a role for neutrophils in AGEP systemic involvement. Physicians should be aware of the possibility of systemic involvement in AGEP and should actively look for signs of extracutaneous reactions.
Human neutrophils interact with both 6-sulfo LacNAc+ DC and NK cells to amplify NK-derived IFNγ: role of CD18, ICAM-1, and ICAM-3
Authors: Claudio Costantini, Federica Calzetti, Omar Perbellini, Alessandra Micheletti, Claudia Scarponi, Silvia Lonardi, Martin Pelletier, Knut Schakel, Giovanni Pizzolo, Fabio Facchetti, William Vermi, Cristina Albanesi, Marco A. Cassatella
Journal: Blood (2010)
A molecular defect in loricrin, the major component of the cornified cell envelope, underlies Vohwinkel's syndrome
Authors: Elena Maestrini, Anthony P. Monaco, John A. McGrath, Akemi Ishida-Yamamoto, Charles Camisa, Alain Hovnanian, Daniel E. Weeks, Mark Lathrop, Jouni Uitto, Angela M. Christiano
Journal: Nature Genetics (1996)
Functional Asplenia in Sickle-Cell Anemia
Authors: Howard A. Pearson, Richard P. Spencer, Eugene A. Cornelius
Journal: New England Journal of Medicine (1969)

Observation of Howell—Jolly bodies in the blood of children with sickle-cell anemia suggested the paradox of splenic hypofunction despite clinical splenomegaly. Spleen scans were performed with a sulfur colloid tagged with radioactive technetium (99mTc). No splenic uptake of the colloid was seen in 11 of 12 children with sickle-cell anemia, although many had enlarged spleens. Twenty-five controls, including children with sickle-cell trait and Hgb SC and Hgb S-β thalassemia diseases, regularly demonstrated splenic uptake. Functional asplenia in children with sickle-cell anemia may be a pertinent factor in the susceptibility to infections — particularly pneumococcal infections — that is characteristic of this disease.
U2AF1 mutations in primary myelofibrosis are strongly associated with anemia and thrombocytopenia despite clustering with JAK2V617F and normal karyotype
Authors: A Tefferi, C M Finke, T L Lasho, E A Wassie, R Knudson, R P Ketterling, C A Hanson, A Pardanani
Journal: Leukemia (2013)
Proliferative glomerulonephritis with monoclonal IgG deposits: A distinct entity mimicking immune-complex glomerulonephritis
Authors: Samih H. Nasr, Glen S. Markowitz, M. Barry Stokes, Surya V. Seshan, Elsa Valderrama, Gerald B. Appel, Pierre Aucouturier, Vivette D. D'Agati
Journal: Kidney International (2003)