tbuckley/cabot-search huggingface dataset:
Are diagnostic and public health bacteriology ready to become branches of genomic medicine?
Authors: Mark J Pallen, Nicholas J Loman
Journal: Genome Medicine (2011)

: Diagnostic medical bacteriology is a conservative discipline. When busy house officers scribble 'M, C & S' on a form, they are requesting two techniques - microscopy and culture of microorganisms - that date back to the late 17th and late 19th century, respectively. The third technique - antibiotic susceptibility testing - has changed little in a half a century. Relatively few front-line diagnostic bacteriology laboratories have embraced molecular methods; on my own campus, the hospital's medical microbiology department does not even possess a thermal cycler!And yet in the research arena, genome sequencing has transformed almost every corner of the biomedical sciences, including the study of bacterial pathogens Furthermore, over the past 5 years, high-throughput (or 'next-generation') sequencing technologies have delivered a step change in our ability to sequence microbial genomes 1. Since arriving in the market place, these technologies have experienced sustained technical improvement, which, twinned with lively competition between alternative platforms, has placed sequencing in a state of 'permanent revolution'.At last, it seems that genomics has come up with a game-changer, a killer app, a disruptive technology that even those long wedded to the Gram stain and the agar plate can no longer ignore. Does this mean we are on the brink of a revolution in diagnostic and public health microbiology, in which high-throughput sequencing usurps the traditional 'M, C & S', or will the discipline's innate conservatism stand firm for decades to come?
STUDIES ON BACTERIOPHAGE
Authors: Walther F. Goebel
Journal: The Journal of Experimental Medicine (1950)

By serological means it has been shown that E. coli B contains an antigen closely related to the protein-lipocarbohydrate complex of Phase II Sh. sonnei. Lysis of E. coli B by three of the T viruses, T(3), T(4), and T(7), can be inhibited by the Phase II dysentery antigen. It has been suggested that the receptor of E. coli B with which these viruses combine is this newly described antigenic component. Two variants of the virus T(3) have also been described, in stocks which have been treated with the Phase II antigen. One of these variants infects both Phase II Sh. sonnei and E. coli B, and the other infects only the latter microorganism; neither of the two variants is inhibited by concentrations of the Phase II antigen of 1 mg. per cc. The distinctive properties of the variants are not hereditary.
Vemurafenib in patients with BRAFV600 mutated metastatic melanoma: an open-label, multicentre, safety study
Authors: James Larkin, Michele Del Vecchio, Paolo A Ascierto, Ivana Krajsova, Jacob Schachter, Bart Neyns, Enrique Espinosa, Claus Garbe, Vanna Chiarion Sileni, Helen Gogas, Wilson H Miller, Mario Mandalà, Geke A P Hospers, Ana Arance, Paola Queirolo, Axel Hauschild, Michael P Brown, Lada Mitchell, Luisa Veronese, Christian U Blank
Journal: The Lancet Oncology (2014)
Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer
Authors: Yixin Wang, Jan GM Klijn, Yi Zhang, Anieta M Sieuwerts, Maxime P Look, Fei Yang, Dmitri Talantov, Mieke Timmermans, Marion E Meijer-van Gelder, Jack Yu, Tim Jatkoe, Els MJJ Berns, David Atkins, John A Foekens
Journal: The Lancet (2005)
Increased Abundance of Distal Sodium Transporters in Rat Kidney during Vasopressin Escape
Authors: CAROLYN A. ECELBARGER, MARK A. KNEPPER, JOSEPH G. VERBALIS
Journal: Journal of the American Society of Nephrology (2001)

Hyponatremia is associated with inappropriately elevated vasopressin levels. A brisk natriuresis precedes the escape from this antidiuresis. Thus, the hypothesis was that the abundance of one or more of the sodium transporters of the distal tubule (a site for fine tuning of sodium balance) would be altered during vasopressin escape. Semiquantitative immunoblotting was used to examine the regulation of abundance of several sodium transporters/channels of the thick ascending limb through the collecting duct in the rat model. Osmotic minipumps to infuse dDAVP, the V2-selective vasopressin agonist (5 ng/h) for the entire experiment, were implanted in Male Sprague-Dawley rats. After 4 d, rats were divided into a control (dry AIN-76 diet/ad libitum water) or a water-loaded (gelled-agar-AIN-76 diet/ad libitum water) group. Rats were killed after 1, 2, 3, or 7 additional days. The water-loaded rats were hyponatremic (plasma Na+, 98 to 122 mmol/L) and manifested the expected early natriuresis and diuresis of vasopressin escape. Water loading (with dDAVP infusion) resulted in increased whole-kidney abundances of the thiazide-sensitive Na-Cl co-transporter, the alpha-subunit of the epithelial sodium channel (ENaC), and the 70-kD dimer of the gamma-subunit of ENaC. No changes were observed for the ss-subunit of ENaC. Similar protein changes have recently been associated with elevated aldosterone levels in rats. However, plasma aldosterone levels were significantly suppressed in this model. These data suggest that several distal sodium reabsorptive mechanisms are upregulated during vasopressin escape; this may help to attenuate the developing hyponatremia resulting from water loading when vasopressin levels are inappropriately elevated.
Phase II Study of the Flk-1 Tyrosine Kinase Inhibitor SU5416 in Advanced Melanoma
Authors: Amy C. Peterson, Susan Swiger, Walter M. Stadler, Milica Medved, Greg Karczmar, Thomas F. Gajewski
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Vascular endothelial growth factor (VEGF) expression is prognostic in melanoma, and the activity of VEGF is mediated in part through the receptor tyrosine kinase Flk-1. A Phase II study of SU5416, a preferential inhibitor of Flk-1, was carried out in patients with metastatic melanoma to determine clinical response, tolerability, and changes in tumor vascular perfusion. Experimental Design: Patients with documented progressive disease and ≤1 prior therapy were eligible. Central nervous system metastases were allowed if stable off medication. SU5416 (145 mg/m2) was administered via a central catheter twice weekly for 8 weeks. Premedication with dexamethasone, diphenhydramine, and a H2 blocker was required because of the Cremophor vehicle. Tumor vascular perfusion was assessed before treatment and during week 8 by dynamic contrast magnetic resonance imaging, and plasma was analyzed for VEGF. Results: Thirty-one patients were enrolled. Two-thirds had received prior therapy, 21 had visceral metastasis, and 14 had an elevated lactate dehydrogenase. Mean absolute lymphocyte counts were decreased (P = 0.002), and glucose levels were increased (P = 0.001) posttherapy, presumably because of steroid premedication. Four vascular adverse events were observed. Of 26 evaluable patients, 1 experienced a partial response, 1 had stable disease, and 5 had a mixed response. Dynamic contrast magnetic resonance imaging in 5 evaluable patients showed decreased tumor perfusion at week 8 (P = 0.024), and plasma VEGF levels were elevated compared with pretherapy (P = 0.008). Conclusions: SU5146 appears to be relatively well tolerated in this population. Although the modest clinical activity and potential effects on tumor vascularity may support additional exploration of VEGF as a target in melanoma, effects from steroid premedication limit further investigation of this agent.
A phase I study of antisense oligonucleotide GTI-2040 given by continuous intravenous infusion in patients with advanced solid tumors
Authors: A.A. Desai, R.L. Schilsky, A. Young, L. Janisch, W.M. Stadler, N.J. Vogelzang, S. Cadden, J.A. Wright, M.J. Ratain
Journal: Annals of Oncology (2005)
Abnormal Adherence of Sickle Erythrocytes to Cultured Vascular Endothelium
Authors: Robert P. Hebbel, Osamu Yamada, Charles F. Moldow, Harry S. Jacob, James G. White, John W. Eaton
Journal: Journal of Clinical Investigation (1980)

The abnormal shape and poor deformability of the sickled erythrocyte (RBC) have generally been held responsible for the microvascular occlusions of sickle cell disease. However, there is no correlation between the clinical severity of this disease and the presence of sickled RBC. In searching for additional factors that might contribute to the pathophysiology of sickle cell disease, we have investigated the possibility that sickle RBC might be less than normally repulsive of the vascular endothelium. After RBC suspensions are allowed to settle onto plates of cultured human endothelial cells, normal RBC are completely removed by as few as six washes. In contrast, sickle RBC remain adherent despite multiple washes. On subconfluent culture plates, normal RBC are distributed randomly, whereas sickle RBC cluster around endothelial cells. Sickle RBC adherence is not enhanced by deoxygenation but does increase with increasing RBC density. The enzymatic removal of membrane sialic acid greatly diminishes the adherence of sickle RBC to endothelial cells, suggesting that sialic acid participates in this abnormal cell-cell interaction. Although net negative charge appears normal, sickle RBC mainfest an abnormal clumping of negative surface charge as demonstrated by localization of cationized ferritin. These abnormalities are reproduced in normal RBC loaded with nonechinocytogenic amounts of calcium. We conclude that sickle RBC adhere to vascular endothelial cells in vitro, perhaps caused by a calcium-induced aberration of membrane topography. This adherence may be a pathogenetic factor in the microvascular occlusions characteristic of sickle cell disease.
THE EFFECT OF SEA STAR COELOMOCYTE EXTRACT ON CELL-MEDIATED RESISTANCE TO LISTERIA MONOCYTOGENES IN MICE
Authors: David O. Willenborg, Robert A. Prendergast
Journal: The Journal of Experimental Medicine (1974)

Mice treated with sea star factor (SSF), a protein extracted from sea star coelomocytes, became highly susceptible to infection with a normally sublethal dose of Listeria monocytogenes. This was in contrast to the expected result of increased resistance originally postulated because of the macrophage-activating properties of SSF. Enhanced susceptibility was seen when SSF was given from 96 h before to 48 h after infection with Listeria. Mice pretreated with SSF failed to develop immunity to Listeria when given a dose of organisms capable of immunizing nontreated mice. Treatment of immune mice with SSF did not alter their immune status. In addition, incubation of immune lymphocytes with SSF in vitro did not alter their ability to adoptively transfer immunity to normal recipients. Immune lymphocytes treated with SSF and then incubated with anti-SSF and C did, however, lose the ability to transfer immunity. These results suggest that SSF enhances infection by binding to T lymphocytes, inhibiting their replication upon contact with Listeria antigen and thus preventing the generation of a population of sensitized lymphocytes capable of effecting anti-Listeria immunity.
Post-inflammatory colonic afferent sensitisation: different subtypes, different pathways and different time courses
Authors: P A Hughes, S M Brierley, C M Martin, S J H Brookes, D R Linden, L A Blackshaw
Journal: Gut (2009)

<h3>Objective:</h3> Intestinal infection evokes hypersensitivity in a subgroup of patients with irritable bowel syndrome (IBS) long after healing of the initial injury. Trinitrobenzene sulfonic acid (TNBS)-induced colitis in rodents likewise results in delayed maintained hypersensitivity, regarded as a model of some aspects of IBS. The colon and rectum have a complex sensory innervation, comprising five classes of mechanosensitive afferents in the splanchnic and pelvic nerves. Their plasticity may hold the key to underlying mechanisms in IBS. Our aim was therefore to determine the contribution of each afferent class in each pathway towards post-inflammatory visceral hypersensitivity. <h3>Design:</h3> TNBS was administered rectally and mice were studied after 7 (acute) or 28 (recovery) days. In vitro preparations of mouse colorectum with attached pelvic or splanchnic nerves were used to examine the mechanosensitivity of individual colonic afferents. <h3>Results:</h3> Mild inflammation of the colon was evident acutely which was absent at the recovery stage. TNBS treatment did not alter proportions of the five afferent classes between treatment groups. In pelvic afferents little or no difference in response to mechanical stimuli was apparent in any class between control and acute mice. However, major increases in mechanosensitivity were recorded from serosal afferents in mice after recovery, while responses from other subtypes were unchanged. Both serosal and mesenteric splanchnic afferents were hypersensitive at both acute and recovery stages. <h3>Conclusions:</h3> Colonic afferents with high mechanosensory thresholds contribute to inflammatory hypersensitivity, but not those with low thresholds. Pelvic afferents become involved mainly following recovery from inflammation, whereas splanchnic afferents are implicated during both inflammation and recovery.
Endothelial Cell Apoptosis in Obstructive Sleep Apnea
Authors: Ali A El Solh, Morohunfolu E Akinnusi, Fadi H Baddoura, Corey R Mankowski
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: Patients with obstructive sleep apnea (OSA) are at increased risk for cardiovascular diseases. Injury of endothelial cells has been advanced as an initial trigger to atherosclerosis.Objectives: To study the association between circulating apoptotic endothelial cells and vasomotor dysfunction as a function of sleep apnea.Methods: Brachial artery flow-mediated dilation was determined in 14 subjects with documented OSA and 10 healthy control subjects at baseline and 8 weeks after continuous positive airway pressure (CPAP) therapy. Quantification of circulating apoptotic endothelial cells (CD146+ Annexin V+) was performed by flow cytometry.Measurements and Main Results: Compared with healthy subjects, patients with OSA had higher numbers of circulating CD146+ Annexin V+ cells (39.2 ± 13.6 cells/mL and17.8 ± 9.4, respectively; p < 0.001). Increased apoptotic endothelial cells correlated moderately with abnormal vascular function (r = −0.61; p = 0.001). A significant correlation was observed between CD146 Annexin V+ cells and the apnea-hypopnea index (r = 0.56; p = 0.004). After 8 weeks of treatment with CPAP, the numbers of circulating apoptotic endothelial cells were reduced significantly from 39.2 ± 13.6 to 22.3 ± 12.9 apoptotic cells per milliliter (p < 0.001) and correlated with improvement in endothelium-dependent vasodilation (r = 0.49; p = 0.07).Conclusions: In patients with OSA, impairment of endothelial-dependent vasodilation correlated with the degree of endothelial cell apoptosis. CPAP therapy led to significant decline in circulating apoptotic endothelial cells. These findings provide an additional mechanism for the predisposition of patients with OSA to premature vascular disease.
A novel method of inducing and assuring total anoxia during in vitro studies of O2 deprivation injury.
Authors: J K Joseph, D Bunnachak, T J Burke, R W Schrier
Journal: Journal of the American Society of Nephrology (1990)

Oxyrase is an enzyme mixture coveted by microbiologists for its unique ability to remove O2 from media in which anaerobic bacteria are grown. The study reported here examined the potential usefulness of Oxyrase as an adjunct to gassing freshly isolated rat proximal tubules (RPT) with 95% N2-5% CO2 in an attempt to achieve totally O2-free conditions (anoxia) before initiating studies on the mechanism of O2 deprivation injury in vitro. RPT, in 6 ml of Krebs-Henseleit buffer (KHB), were initially gassed with 95% N2-5% CO2 at 1.5 liters/min for 5 min and incubated for 15 to 30 min at 37 degrees C in a shaking water bath, pO2 decreased from approximately 400 to 80 mm Hg. If RPT were present in the KHB, pO2 was even lower, i.e., approximately 50 mm Hg. Addition of increasing concentrations of Oxyrase (300 to 1,500 mU) to KHB alone, that is, without RPT, reduced pO2 from 80 mm Hg to less than 5 mm Hg; increasing the gas rate from 1.5 to 3.0 liter/min of 95% N2-5% CO2, the concentration of Oxyrase to 1,800 mU, and adding RPT reduced pO2 to zero. In this latter condition, pO2 remained unmeasurable during the 20 min of study and neither pH nor pCO2 changed compared with control values. Oxyrase (1,800 mU) had no effect on lactate dehydrogenase release, a sign of membrane injury, in normoxic RPT in KHB. We conclude that anoxia can easily be achieved by the addition of Oxyrase to KHB in which RPT are suspended, if the appropriate concentration of Oxyrase is added and if the RPT are gassed with 95% N2-5% CO2. This concentration of Oxyrase exerts no detrimental effects on RPT gassed with 95% O2-5% CO2.
447 DIFFERENCES IN DEMOGRAPHICS AND TREATMENT OUTCOME OF CHRONIC HEPATITIS C (CHC) PATIENTS OF DIFFERENT EUROPEAN ORIGIN TREATED WITH PEGINTERFERON ALFA-2A (40KDA) AND RIBAVIRIN (PEG/RBV)
Authors: T. Lutz, K. Boeker, G. Moog, A. Baumgarten, C. Eisenbach, W. Schmidt, M. Waizmann, B. Bokemeyer, S. Pape, M. Roessle, A. Stoehr, J. Lohmeyer, T. Witthoeft, B. Möller, H. Loehr, E. Schott, U. Alshuth, D. Hueppe
Journal: Journal of Hepatology (2011)
Generation of recombinant, enzymatically active human thyroid peroxidase and its recognition by antibodies in the sera of patients with Hashimoto's thyroiditis.
Authors: K D Kaufman, B Rapoport, P Seto, G D Chazenbalk, R P Magnusson
Journal: Journal of Clinical Investigation (1989)

A full-length cDNA clone for human thyroid peroxidase (TPO) inserted into the mammalian cell expression vector pECE was stably transfected into Chinese hamster ovary (CHO) cells. Clones were assayed for human TPO mRNA, TPO protein, and TPO enzymatic activity. One subclone, expressing the highest TPO enzymatic activity, was used in further studies. FACS analysis of these cells preincubated in Hashimoto's serum revealed approximately 100-fold greater fluorescence compared with controls, indicating that recombinant TPO is expressed on the cell surface. Particulate antigen was extracted from these cells and studied by Western blot analysis using a panel of Hashimoto's sera of known antimicrosomal antibody (anti-MSA) titer. Under nonreducing conditions a broad, immunoreactive band of approximately 200 kD was observed, as well as a doublet of approximately 110 kD. All of the 36 Hashimoto's sera tested reacted with these bands, most in proportion to their anti-MSA titer. Six normal sera tested against this antigen(s) were nonreactive, as were the Hashimoto's sera tested against nontransfected CHO cells. Western blots under reducing conditions revealed a considerably diminished signal, with some of the sera of lower anti-MSA titer becoming negative, the loss of the 200-kD broad band, and the apparent conversion of the 110-kD doublet into a single band. Preincubation of cells in tunicamycin revealed no decrease in TPO immunoreactivity. In conclusion, we expressed enzymatically active human TPO in nonthyroidal eukaryotic cells. Our data prove that functionally active TPO is a major component of the thyroid microsomal antigen.
Extensively Drug-Resistant Tuberculosis: A New Face to an Old Pathogen
Authors: Sheela Shenoi, Gerald Friedland
Journal: Annual Review of Medicine (2009)

The presence and consequences of resistance to drugs used for the treatment of tuberculosis have long been neglected. The recent detection and recognition of widespread multiple-drug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis have raised interest and concern among clinicians and public health authorities globally. In this article, we describe the current global status of drug-resistant tuberculosis. We discuss the development of resistance, current management, and strategies for control.
Twisting and Ironing: Doxorubicin Cardiotoxicity by Mitochondrial DNA Damage
Authors: Karin C. Nitiss, John L. Nitiss
Journal: Clinical Cancer Research (2014)

Anthracyclines are active clinical agents that have multiple mechanisms of cytotoxicity. Cardiotoxicity by anthracyclines limits the therapeutic potential of these agents, but mechanisms leading to cardiotoxicity remain controversial. Transgenic mice that lack mitochondrial topoisomerase I are hypersensitive to doxorubicin cardiotoxicity, providing support for cardiotoxicity arising from damage of mitochondrial DNA.
Bile acid glycine and taurine conjugates in serum of patients with primary biliary cirrhosis: effect of ursodeoxycholic treatment.
Authors: Y Chretien, R Poupon, M F Gherardt, O Chazouilleres, D Labbe, A Myara, F Trivin
Journal: Gut (1989)

We have applied a specific and accurate high pressure liquid chromatographic technique to determine fasting serum glycine and taurine conjugates of individual bile acids in patients with primary biliary cirrhosis before and during ursodeoxycholic acid therapy. The study was carried out in nine patients in whom the diagnosis of primary biliary cirrhosis was established according to accepted criteria. After one year of UDCA therapy liver function tests significantly improved. Total serum bile acid concentration did not change significantly (29.2 (31.5) v 28.3 (26.4) microM). Total UDCA (1.7 (2.2) v 13.3 (14.5) microM) and glyco UDCA (0.8 (1.6) v 10.9 (11.4 microM) but not tauro UDCA levels increased significantly (p less than 0.01); UDCA (7.7 (12.6) v 40.2 (12.7)%) became the major species of the circulating bile acids. Primary bile acids (23 (28.3) v 11.2 (10.5) and their glycoconjugates fell significantly (p less than 0.01). There were no significant changes in the concentrations of conjugates of the secondary bile acids (4.5 (3.8) v 3.9 (3.0]. Our study shows that oral administration of UDCA to patients with primary biliary cirrhosis induced marked changes in the circulating pool of endogenous bile acids together with improvement in liver function test values. The data also suggest that the beneficial effect of longterm administration of UDCA in these patients might be mediated through changes in the circulating primary bile acids and UDCA rather than through changes in the circulating secondary bile acids, deoxycholate and lithocholate.
B cell growth factors and B cell differentiation factor from human T hybridomas. Two distinct kinds of B cell growth factor and their synergism in B cell proliferation.
Authors: M Okada, N Sakaguchi, N Yoshimura, H Hara, K Shimizu, N Yoshida, K Yoshizaki, S Kishimoto, Y Yamamura, T Kishimoto
Journal: The Journal of Experimental Medicine (1983)

Human T hybridomas secreting B cell growth factors (BCGF) and B cell differentiation factor (BCDF) have been established. Hybrid clones 77-A, 94-C, and 98-F secreted BCGF that induced proliferation of anti-IgM-stimulated normal B cells. The culture supernatant from 77-A cells could also maintain continuous proliferation of colony-forming B cells, but the factor from 94-C could not. The addition of the supernatant from 94-C cells to that from 77-A cells, however, synergistically augmented the proliferation of colony-forming B cells, demonstrating the existence of two distinct kinds of BCGF and the synergism between them. These supernatants, however, showed no interleukin 2 (IL-2) or BCDF activity. A hybrid clone, 90-E, secreted BCDF. The culture supernatant induced Ig production in Cowan I-stimulated normal B cells or in a transformed B cell line, CESS. However, the supernatant had no BCGF or IL-2 activity. Anti-Ig-stimulated B cells, but not IL-2-dependent T cells, absorbed BCGF activity and CESS cells absorbed BCDF activity but not BCGF activity in the culture supernatants from T hybridomas. Taken collectively, the results demonstrated that IL-2, BCGF, and BCDF were different molecules and acceptors specific for the each molecule are present on the each target cell.