tbuckley/cabot-search huggingface dataset:
If the proper study of mankind is man, the proper study of cholesterol is the liver
Authors: G. S. Tint
Journal: Hepatology (1986)

A two-year-old boy presented with severe failure to thrive, developmental delay, anemia, hepatosplenomegaly, central cataracts, and dysmorphic features. Quantitative analyses of urinary organic acids revealed massive excretion of mevalonic acid, a metabolic precursor of cholesterol and nonsterol isoprenes: 46,000 to 56,200 mmol per mole of creatinine, as compared with 0.2 to 0.3 mmol per mole in normal children. The mevalonic acid concentration in plasma was also greatly increased at 440 μmol per liter (normal, &lt;0.05). The activity of mevalonate kinase, the enzyme that catalyzes the first step in mevalonate metabolism, was severely deficient in the patient's fibroblasts, lymphocytes, and lymphoblasts. In the subsequent pregnancy of the patient's mother, gas chromatography-mass spectrometry demonstrated a marked elevation of mevalonic acid in the mother's urine and a 3000-fold elevation, as compared with control levels in the amniotic fluid, suggesting that the fetus was affected. The diagnosis was confirmed by demonstration of the deficiency of mevalonate kinase in amniocytes and ultimately in liver from the abortus. Intermediate activities of the enzyme in both parents indicated an autosomal recessive mode of inheritance. These observations identify an inherited disorder of cholesterol and nonsterol isoprene biosynthesis in humans.
Role of Sleep Apnea and Continuous Positive Airway Pressure Therapy in the Incidence of Stroke or Coronary Heart Disease in Women
Authors: Francisco Campos-Rodriguez, Miguel A. Martinez-Garcia, Nuria Reyes-Nuñez, Isabel Caballero-Martinez, Pablo Catalan-Serra, Carmen V. Almeida-Gonzalez
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: It is unknown whether obstructive sleep apnea (OSA) may be a risk factor for incident cardiovascular events in women.Objectives: We sought to investigate whether OSA increases the incidence of a composite of stroke or coronary heart disease (CHD) in women, and the role of continuous positive airway pressure (CPAP) treatment on this association.Methods: This was a prospective, observational study conducted in two Spanish teaching hospitals between 1998 and 2007. Consecutive women referred for suspected OSA and free of previous stroke and CHD were analyzed. Women with an apnea–hypopnea index (AHI) less than 10 comprised the control group, and those with an AHI greater than or equal to 10 were diagnosed with OSA and classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/d or not prescribed). The follow-up ended in December 2010.Measurements and Main Results: A total of 967 women were studied (median follow-up, 6.8 yr; interquartile range, 5.2–8.2). The untreated OSA group showed a greater incidence rate of the composite outcome than the control group (2.19 vs. 0.54 per 100 person-years; P < 0.0005). Compared with the control group, the fully adjusted hazard ratios for the composite outcome incidence were 2.76 (95% confidence interval [CI], 1.35–5.62) for the untreated OSA group, and 0.91 (95% CI, 0.43–1.95) for the CPAP-treated group. When the type of cardiovascular event was separately assessed, untreated OSA showed a stronger association with incident stroke (adjusted hazard ratio, 6.44; 95% CI, 1.46–28.3) than with CHD (adjusted hazard ratio, 1.77; 95% CI, 0.76–4.09).Conclusions: In women, untreated OSA is associated with increased incidence of serious cardiovascular outcomes, particularly incident stroke. Adequate CPAP treatment seems to reduce this risk.
Endothelium-derived relaxing factor and protection against contractions induced by histamine and serotonin in the human internal mammary artery and in the saphenous vein.
Authors: Z H Yang, D Diederich, K Schneider, R Siebenmann, P Stulz, L von Segesser, M Turina, F R Bühler, T F Lüscher
Journal: Circulation (1989)

We investigated the release of endothelium-derived relaxing factor (EDRF) in response to serotonin and histamine in the human internal mammary artery and saphenous vein. The arteries and veins were obtained intraoperatively and were suspended in organ chambers to record isometric tension. In mammary arteries, histamine (10(-8) to 3 X 10(-6) M) induced relaxations in rings with (70 +/- 5%, IC50, 6.5 +/- 0.2) but not without endothelium (p less than 0.005 for rings with compared with those without endothelium, n = 7-10). The response was inhibited by methylene blue or hemoglobin, but not meclofenamate, and, therefore, EDRF was delineated as the mediator. Because chlorpheniramine but not cimetidine inhibited the response, EDRF was released by the H1-histaminergic receptor (n = 5-8). In contrast, in saphenous veins, histamine caused only weak or absent endothelium-dependent relaxations, but contractions were enhanced in rings with endothelium (p less than 0.05, n = 6). Serotonin did not induce endothelium-dependent relaxations, but contractions were markedly greater in veins compared with arteries (p less than 0.005, n = 6). The endothelium inhibited the maximal contraction to serotonin in arteries (p less than 0.034) but not in veins. Thus, EDRF protects against contractions induced by histamine and serotonin in the mammary artery but not in the saphenous vein. This may be important for improved graft function and patency of the artery compared with that of the vein.
The lymphocyte transformation test in the diagnosis of drug hypersensitivity
Authors: W. J. Pichler, J. Tilch
Journal: Allergy (2004)

Diagnosis of drug hypersensitivity is difficult, as an enormous amount of different drugs can elicit various immune-mediated diseases with distinct pathomechanism. The lymphocyte transformation test (LTT) measures the proliferation of T cells to a drug in vitro--from which one concludes to a previous in vivo reaction due to a sensitization. This concept of the LTT has been confirmed by the generation of drug-specific T-cell clones and the finding that drugs can directly interact with the T-cell receptor, without previous metabolism or need to bind to proteins. In this review, technical aspects and usefulness of this test for the diagnosis of drug hypersensitivity are discussed. The main advantage of this test is its applicability with many different drugs in different immune reactions, as drug-specific T cell are almost always involved in drug hypersensitivity reactions. Its main disadvantages are that an in vitro proliferation of T cells to a drug is difficult to transfer to the clinical situation and that the test per se is rather cumbersome and technically demanding. In addition, its sensitivity is limited (for beta-lactam allergy it is in the range of 60-70%), - although at least in our hands - it is higher than of other tests for drug hypersensitivity diagnosis. Consequently, drug hypersensitivity diagnosis needs to rely on a combination of history and different tests, as none of the single tests available has per se a sufficiently good sensitivity. Within this setting, the LTT has proven to be a useful test for the diagnosis of drug hypersensitivity reactions and helped to better understand these reactions. Further work on the simplification of this test and systematic evaluation of its sensitivity and specificity in some main groups of drugs are necessary to make this test more widely available.
Expression of the Hypoxia Marker Carbonic Anhydrase 9 Is Associated with Anaplastic Phenotypes in Meningiomas
Authors: Heon Yoo, Gilson S. Baia, Justin S. Smith, Michael W. McDermott, Andrew W. Bollen, Scott R. VandenBerg, Kathleen R. Lamborn, Anita Lal
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Hypoxia in the tumor microenvironment triggers a variety of genetic and adaptive responses that regulate tumor growth. Tumor hypoxia is often associated with more malignant phenotypes, resistance to therapy, and poor survival. The purpose of this study was to evaluate the prevalence of hypoxia in meningiomas using the endogenous hypoxia marker carbonic anhydrase 9 (CA9) and to relate the expression of CA9 to tumor vascularity, histopathologic grade, and clinical variables, such as recurrent tumor status. Experimental Design: Expression of CA9 and CD34, an endothelial cell marker, was examined in serial paraffin-embedded sections by immunohistochemistry in 25 grade 1, 17 grade 2, and 20 grade 3 meningiomas. Areas of immunoreactivity were semiquantitatively scored and correlated to clinical variables using Statistical Analysis System statistical software. Results: Approximately 50% (29 of 62) of all meningiomas contained regions of hypoxia as judged by expression of CA9, and this expression was significantly associated with higher-grade histology (P = 0.001). In contrast, vascularity, as assessed by the percentage of vascular hotspots, was inversely associated with tumor grade (P = 0.023) and was not associated with CA9 expression. Among lower-grade meningiomas, CA9 expression tended to be more common in recurrent tumors. Conclusions: Tumor hypoxia is an endogenous feature of meningiomas, and therapeutic regimens should include strategies to target the subpopulation of hypoxic as well as the normoxic cells within the tumor. Hypoxia in meningiomas is associated with an aggressive phenotype. Further studies to define the contribution of hypoxia to meningioma pathophysiology are warranted.
Vaccination preserves CD4 memory T cells during acute simian immunodeficiency virus challenge
Authors: Joseph J. Mattapallil, Daniel C. Douek, Alicia Buckler-White, David Montefiori, Norman L. Letvin, Gary J. Nabel, Mario Roederer
Journal: The Journal of Experimental Medicine (2006)

Acute simian immunodeficiency virus (SIV)/human immunodeficiency virus infection is accompanied by a massive destruction of CD4 memory T cells across all the tissue compartments. These early events set the course toward disease progression and immunodeficiency. Here, we demonstrate that prior vaccination reduces this destruction during acute SIV Mac251 infection, leading to better survival and long-term outcome. Systemic vaccination with a DNA-prime recombinant adenovirus boost regimen preserved memory CD4 T cells throughout the body. The vaccine regimen induced broad CD4 and CD8 T cell responses in all tissues examined and, importantly, induced antibodies that neutralized the primary isolate of SIV used for challenge. Finally, we demonstrate that the extent of preservation of the CD4 memory compartment during the acute phase provides a strong predictor for subsequent progression to death. Our data provide a mechanism to explain clinical observations that acute-phase viral loads predict long-term disease progression and underscore the need for interventions that protect against early destruction of CD4 memory T cells during acute infection.
Rapid D-dimer testing as an adjunct to clinical findings in excluding pulmonary embolism
Authors: A. F. Lennox, A. N. Nicolaides
Journal: Thorax (1999)

Background.A study was undertaken to assess the usefulness of the SimpliRED D-dimer test, arterial oxygen tension, and respiratory rate measurement for excluding pulmonary embolism (PE) and venous thromboembolism (VTE).Methods.Lung scans were performed in 517 consecutive medical inpatients with suspected acute PE over a one year period.Predetermined end points for objectively diagnosed PE in order of precedence were (1) a post mortem diagnosis, (2) a positive pulmonary angiogram, (3) a high probability ventilation perfusion lung scan when the pretest probability was also high, and (4) the unanimous opinion of an adjudication committee.Deep vein thrombosis (DVT) was diagnosed by standard ultrasound and venography.Results.A total of 40 cases of PE and 37 cases of DVT were objectively diagnosed.The predictive value of a negative SimpliRED test for excluding objectively diagnosed PE was 0.99 (error rate 2/249), that of PaO 2 of ≥80 mm Hg (10.7 kPa) was 0.97 (error rate 5/160), and that of a respiratory rate of ≤20/min was 0.95 (error rate 14/308).The best combination of findings for excluding PE was a negative SimpliRED test and PaO 2 ≥80 mm Hg, which gave a predictive value of 1.0 (error rate 0/93).The predictive value of a negative SimpliRED test for excluding VTE was 0.98 (error rate 5/249).Conclusions.All three of these observations are helpful in excluding PE.When any two parameters were normal, PE was very unlikely.In patients with a negative SimpliRED test and PaO 2 ≥80 mm Hg a lung scan is usually unnecessary.Applications of this approach for triage in the preliminary assessment of suspected PE could lead to a reduced rate of false positive diagnoses and considerable resource savings.(
Efficacy of single-dose SA 14–14–2 vaccine against Japanese encephalitis: a case control study
Authors: Mahendra Bahadur Bista, MK Banerjee, Sun Heang Shin, JB Tandan, Myung Ho Kim, Young Mo Sohn, Hee Choul Ohrr, Jin Ling Tang, Scott B Halstead
Journal: The Lancet (2001)
Muscle and Skin Sympathetic Nerve Traffic During the “White-Coat” Effect
Authors: Guido Grassi, Carlo Turri, Sabrina Vailati, Raffaella Dell’Oro, Giuseppe Mancia
Journal: Circulation (1999)

Background —Sphygmomanometric blood pressure measurements induce an alerting reaction and thus an increase in the patient’s blood pressure and heart rate. Whether and to what extent this “white-coat” effect is accompanied by detectable changes in sympathetic nerve traffic has never been investigated. Methods and Results —In 10 mild untreated essential hypertensives (age 37.9±3.8 years, mean±SEM), we measured arterial blood pressure (by Finapres), heart rate (by ECG), and postganglionic muscle and skin sympathetic nerve activity via microneurography. Measurements were performed with the subject supine during (1) a 15-minute control period, (2) a 10-minute visit by a doctor unfamiliar to the patient who was in charge of measuring his or her blood pressure by sphygmomanometry, and (3) a 15-minute recovery period after the doctor’s departure. The entire procedure was performed twice at a 45-minute interval to obtain, in separate periods, muscle or skin sympathetic nerve traffic recordings, whose sequence was randomized. The doctor’s visit induced a sudden, marked, and prolonged pressor and tachycardic response, accompanied by a significant increase in skin sympathetic nerve traffic (+38.6±6.7%, P &lt;0.01). In contrast, muscle sympathetic nerve traffic was significantly inhibited (−25.5±4.1%, P &lt;0.01). All changes persisted throughout the doctor’s visit and, with the exception of skin sympathetic nerve traffic, showed a slow rate of disappearance after the doctor’s departure. Conclusions —Thus, the pressor and tachycardic responses to the alerting reaction that accompanies sphygmomanometric blood pressure measurement is characterized by a behavior of the adrenergic nervous system that causes muscle sympathoinhibition and skin sympathoexcitation.
Prognostic value of remnant-like lipoprotein particle levels in patients with coronary artery disease and type ii diabetes mellitus
Authors: Hironobu Fukushima, Seigo Sugiyama, Osamu Honda, Shunichi Koide, Shinichi Nakamura, Tomohiro Sakamoto, Michihiro Yoshimura, Hisao Ogawa, Daisuke Fujioka, Kiyotaka Kugiyama
Journal: Journal of the American College of Cardiology (2004)
Risk Factors for Type 2 Diabetes in a Sixth- Grade Multiracial Cohort
Authors: Francine R Kaufman, Kathryn Hirst, Barbara Linder, Tom Baranowski, Dan M Cooper, Gary D Foster, Linn Goldberg, Joanne S Harrell, Marsha D Marcus, Roberto P Treviño
Journal: Diabetes Care (2009)

HEALTHY is a 3-year middle school intervention program designed to reduce risk factors for type 2 diabetes. The prevalence of diabetes risk factors at baseline in a cohort of 6,358 sixth-grade students is reported.
Evolutionary Diversification of DNA Methyltransferases in Eukaryotic Genomes
Authors: Loïc Ponger, Wen-Hsiung Li
Journal: Molecular Biology and Evolution (2005)

In eukaryotes, C5-cytosine methylation is a common mechanism associated with a variety of functions such as gene regulation or control of genomic stability. Different subfamilies of eukaryotic methyltransferases (MTases) have been identified, mainly in metazoa, plants, and fungi. In this paper, we used hidden Markov models to detect MTases in completed or almost completed eukaryotic genomes, including different species of Protozoa. A phylogenetic analysis of MTases enabled us to define six subfamilies of MTases, including two new subfamilies. The dnmt1 subfamily that includes all the known MTases with a maintenance activity seems to be absent in the Protozoa. The dnmt2 subfamily seems to be the most widespread, being present even in the nonmethylated Dictyostelium discoideum. We also found two dnmt2 members in the bacterial genus Geobacter, suggesting that horizontal transfers of MTases occurred between eukaryotes and prokaryotes. Even if the direction of transfer cannot be determined, this relationship might be useful for understanding the function of this enigmatic subfamily of MTases. Globally, our analysis reveals a great diversity of MTases in eukaryotes, suggesting the existence of different methylation systems. Our results also suggest acquisitions and losses of different MTases in every eukaryotic lineage studied and that some eukaryotes appear to be devoid of methylation.
Tumor Necrosis Factor-α Contributes to Ischemia- and Reperfusion-Induced Endothelial Activation in Isolated Hearts
Authors: Christian Kupatt, Helmut Habazettl, Axel Goedecke, Dieter A. Wolf, Stefan Zahler, Peter Boekstegers, Ralph A. Kelly, Bernhard F. Becker
Journal: Circulation Research (1999)

Abstract —During myocardial reperfusion, polymorphonuclear neutrophil (PMN) adhesion involving the intercellular adhesion molecule-1 (ICAM-1) may lead to aggravation and prolongation of reperfusion injury. We studied the role of early tumor necrosis factor-α (TNF-α) cleavage and nuclear factor-κB (NF-κB) activation on ICAM-1 expression and venular adhesion of PMN in isolated hearts after ischemia (15 minutes) and reperfusion (30 to 480 minutes). NF-κB activation (electromobility shift assay) was found after 30 minutes of reperfusion and up to 240 minutes. ICAM-1 mRNA, assessed by Northern blot, increased during the same interval. Functional effect of newly synthesized adhesion molecules was found by quantification (in situ fluorescence microscopy) of PMN, given as bolus after ischemia, which became adherent to small coronary venules (10 to 50 μm in diameter). After 480 minutes of reperfusion, ICAM-1–dependent PMN adhesion increased 2.5-fold compared with PMN adhesion obtained during acute reperfusion. To study the influence of NF-κB on PMN adhesion, we inhibited NF-κB activation by transfection of NF-κB decoy oligonucleotides into isolated hearts using HJV-liposomes. Decoy NF-κB but not control oligonucleotides blocked ICAM-1 upregulation and inhibited the subacute increase in PMN adhesion. Similar effects were obtained using BB 1101 (10 μg), an inhibitor of TNF-α cleavage enzyme. These data suggest that ischemia and reperfusion in isolated hearts cause liberation of TNF-α, activation of NF-κB, and upregulation of ICAM-1, an adhesion molecule involved in inflammatory response after ischemia and reperfusion.
Fiscal Analysis of Establishment of a Double-Balloon Enteroscopy Program and Reimbursement
Authors: Mark E. Benson, Wendy Horton, Jill Gluth, Patrick R. Pfau, Sigurdur Einarsson, Michael R. Lucey, Anurag Soni, Mark Reichelderfer, Deepak V. Gopal
Journal: Clinical Gastroenterology and Hepatology (2012)
THE CONSERVATIVE TREATMENT OF TUBERCULOSIS OF JOINTS
Authors: W. S. Fenwick
Journal: BMJ (1913)

TEN to fifteen years ago it was customary to treat suLrgical tuberculosis of joints almost in the sarme way as cancer.One was advised to operate and remove tissues widelyeven amputate-as soon as the diagnosis was made.In recent years, hlowever, this practice has given way more and more to conservative measures, alnd particularly in sturgical tubercle in childhood, of which I w'islh more especially to speak.There is still no doubt tllat in adults, where tinre is important, and. the procluction of a sSeedy result essential, and 'where growing opiplhyses have not to be reckoned with, tlle more radical measures are permissible, alnd even-advisable, but in cllildren I am becoming more andc more convinced that extensive operative procedures are rarely, if ever, called -for, and when necessity arises for tlhenm.it is due to some gross error in diagnosis or treatment at the outset of the disease.
Managing an extensively drug-resistant tuberculosis outbreak: the public health face of the medal
Authors: Luigi R. Codecasa, Giorgio Ciconali, Ester Mazzola, Maurizio Ferrarese, Daniela Cirillo, Emanuele Borroni, Giovanni P. Gesu, Jean-Pierre Zellweger, Rosella Centis, Marino Faccini
Journal: European Respiratory Journal (2014)

We read with interest the letter by Esposito et al. [1], reporting on the clinical management of a paediatric case of extensively drug-resistant tuberculosis (XDR-TB) in Milan, Italy, who faced a life-threatening condition [2 3] that required access to an electronic Consilium [4]. The article is important as it describes a complex epidemic originated by a really difficult-to-treat case who had an intensive social life in a large city, thus making it necessary to perform a vast tracing of contacts, stratified into circles at different risk of exposure. XDR-TB outbreaks absorb important resources and public health/clinical coordination is essential to minimise effects <http://ow.ly/B5Mqh> The authors would like to acknowledge the following co-investigators: Susanna Esposito and Samantha Bosis (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy); Elia Stupka, Davide Cittaro and Paolo Miotto (IRCCS San Raffaele Scientific Institute, Milan Italy); Stefan Niemann and Thomas Khol (Molecular Mycobacteriology, Borstel, Germany). The authors would also like to thank Maria Gramegna, Alessandra Piatti and Liliana Coppola (General Health Direction, Lombardy Region, Milan, Italy) and all the Public Health Nurses of the Milan 3rd Public Health District and of the TB Reference Centre who participated in the management of the Milan outbreak.