tbuckley/cabot-search huggingface dataset:
STUDIES ON THE MECHANISM OF RECOVERY IN PNEUMOCOCCAL PNEUMONIA
Authors: W. Barry Wood, Charlotte McLeod, Edwin N. Irons
Journal: The Journal of Experimental Medicine (1946)

The phagocytosis which occurs in the lungs of rats receiving sulfonamide is due neither to an opsonizing action of the sulfonamides nor to type-specific antibody. The evidence presented indicates that the destruction of the pneumococci is brought about by a phagocytic mechanism independent of both opsonization and capsular injury.
Demonstration of elastin gene expression in human skin fibroblast cultures and reduced tropoelastin production by cells from a patient with atrophoderma.
Authors: M G Giro, A I Oikarinen, H Oikarinen, G Sephel, J Uitto, J M Davidson
Journal: Journal of Clinical Investigation (1985)

Atrophoderma is a rare dermal disorder characterized by a patchy distribution of areas apparently devoid of elastic fibers. Skin fibroblast cultures were established from the normal and affected dermis of a patient with this disorder. Human tropoelastin was identified in culture medium by use of electroblotting and anti-elastin antisera. An enzyme-linked immunosorbent assay was used to establish that significantly less elastin accumulated in the media of cultured cells from lesional fibroblasts over a 3-d period. Since elastin biosynthesis in most tissues is under pretranslational control, molecular hybridization to a nick-translated genomic elastin probe was performed; however, elastin messenger RNA levels were equivalent in both cell strains. Both strains produced less elastin than did normal skin fibroblasts. Extracellular proteolysis of elastin was evaluated as a possible mechanism. Elastase activity was increased and porcine tropoelastin was degraded four times faster, on a per-cell basis, in lesional fibroblast cultures than in cells derived from an unaffected site. The two cell strains exhibited no significant differences in collagen production or collagenase activity. These results are the first demonstration of elastin production by cultured human skin fibroblasts, and they suggest that the primary defect in atrophoderma may be a result of enhanced degradation of newly synthesized elastin precursors.
Recommendations for clinical use of data on neutralising antibodies to interferon-beta therapy in multiple sclerosis
Authors: Chris H Polman, Antonio Bertolotto, Florian Deisenhammer, Gavin Giovannoni, Hans-Peter Hartung, Bernhard Hemmer, Joep Killestein, Henry F McFarland, Joel Oger, Andrew R Pachner, John Petkau, Anthony T Reder, Stephen C Reingold, Huub Schellekens, Per Soelberg Sørensen
Journal: The Lancet Neurology (2010)
Pharmacological protection of mitochondrial function in hypoxic heart muscle: Effect of verapamil, propranolol, and methylprednisolone
Authors: W. G. NAYLER, E. FASSOLD, C. YEPEZ
Journal: Cardiovascular Research (1978)

Experiments were undertaken to determine if drugs (verapamil, propranolol, and methylprednisolone sodium saccinate) that protect the fine ultrastructure of heart muscle against damage caused by hypoxia, protect mitochondrial function. Mitochondrial function was assessed in terms of oxidative phosphorylating and Ca2 +-accumulating activities. Isolated rabbit hearts were used, and hypoxic conditions induced by reducing the perfusate PO2 from 80.8 to 0.80 kPa (600 to 6 mmHg). The drugs were either added at the start of the hypoxic perfusion or (verapamil and propranolol) the rabbits were pretreated with them. Verapamil, propranolol and, to a lesser extent, methylprednisolone sodium succinate, provided protection evidenced by the maintainance of near normal mitochondrial oxidative phosphorylating and Ca2 +-accumulating activities after 60 min hypoxic perfusion. When added directly to mitochondria isolated from hypoxic-perfused muscle, the drugs had no effect.
Autosomal dominant polycystic kidney disease
Authors: A K Saggar-Malik, S Jeffery, M A Patton
Journal: BMJ (1994)

When the BMJ last published an editorial on adult autosomal dominant polycystic kidney disease1 there was no chromosomal assignment for the disorder. Two have since been recognised. The first, designated PKD-1,2 has been localised to a narrow region of about half a million base pairs on the short arm of chromosome 16, but the specific gene has not yet been discovered. A second locus was postulated in 1988,3 and in the past few months two groups have independently confirmed that a second locus exists on chromosome 4q13-q23.4,5 What proportion of cases that this new locus accounts for and whether other loci exist are unknown.

The discovery of this second locus will improve the accuracy of presymptomatic …
Mutations in SLC20A2 link familial idiopathic basal ganglia calcification with phosphate homeostasis
Authors: Cheng Wang, Yulei Li, Lei Shi, Jie Ren, Monica Patti, Tao Wang, João R M de Oliveira, María-Jesús Sobrido, Beatriz Quintáns, Miguel Baquero, Xiaoniu Cui, Xiang-Yang Zhang, Lianqing Wang, Haibo Xu, Junhan Wang, Jing Yao, Xiaohua Dai, Juan Liu, Lu Zhang, Hongying Ma, Yong Gao, Xixiang Ma, Shenglei Feng, Mugen Liu, Qing K Wang, Ian C Forster, Xue Zhang, Jing-Yu Liu
Journal: Nature Genetics (2012)
Atacicept in multiple sclerosis (ATAMS): a randomised, placebo-controlled, double-blind, phase 2 trial
Authors: Ludwig Kappos, Hans-Peter Hartung, Mark S Freedman, Alexey Boyko, Ernst Wilhelm Radü, Daniel D Mikol, Marc Lamarine, Yann Hyvert, Ulrich Freudensprung, Thomas Plitz, Johan van Beek
Journal: The Lancet Neurology (2014)
Trabectedin plus pegylated liposomal doxorubicin in the treatment of patients with partially platinum-sensitive ovarian cancer: current evidence and future perspectives
Authors: J. Sehouli, V. Alfaro, A. González-Martín
Journal: Annals of Oncology (2011)

The effectiveness of platinum re-treatment in relapsed ovarian cancer depends on relapse-free/treatment-free intervals. Platinum agents can be effectively readministered to platinum-sensitive patients (relapsing >12 months after platinum), but efficacy is lower in partially platinum-sensitive (PPS) disease (relapsing 6-12 months after platinum). There is no clear standard treatment challenging PPS patients. Survival data in this subset with chemotherapy combinations such as pegylated liposomal doxorubicin (PLD) plus carboplatin or gemcitabine plus PLD are available from phase II trials ranging from 16 to 21 months. Recent results from OVA-301 phase III randomized trial evaluating trabectedin plus PLD showed the longest median overall survival ever reported in PPS patients (23 months). Subsequent chemotherapy (including platinum-based regimens) was administered later and survival in patients receiving third-line platinum was longer in patients treated with trabectedin plus PLD compared with those treated with PLD alone. These results suggest that prolonging platinum-free interval (PFI) with an effective non-platinum regimen improves outcome with subsequent third-line platinum treatment. An ongoing phase III trial (INOVATYON) aims to demonstrate if the results observed with trabectedin plus PLD in PPS patients are due to PFI extension, and if PFI extension with non-platinum combination prolongs response to subsequent platinum and survival in this population.
High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers
Authors: E. Castro, S. Jugurnauth-Little, Q. Karlsson, F. Al-Shahrour, E. Piñeiro-Yañez, F. Van de Poll, D. Leongamornlert, T. Dadaev, K. Govindasami, M. Guy, R. Eeles, Z. Kote-Jarai
Journal: Annals of Oncology (2015)
The use of prolotherapy in the sacroiliac joint
Authors: M Cusi, J Saunders, B Hungerford, T Wisbey-Roth, P Lucas, S Wilson
Journal: British Journal of Sports Medicine (2008)

In this study the effectiveness of prolotherapy in the treatment of deficient load transfer of the sacroiliac joint (SIJ) was determined.A prospective descriptive study.Authors' private practice.25 patients who consented to treatment and attended for at least one follow-up visit and assessment.From April 2004 to July 2007.Three injections of hypertonic dextrose solution into the dorsal interosseous ligament of the affected SIJ, under CT control, 6 weeks apart.Quebec Back Pain Disability Scale, Roland-Morris 24, Roland-Morris 24 Multiform questionnaires and clinical examination by two authors independently.All patients included in this study attended at least one follow-up visit at 3, 12 or 24 months.. The number of patients at follow-up decreased at 12 and 24 months. Functional questionnaires demonstrated significant improvements for those followed-up at 3, 12 and 24 months (p<0.05). Clinical scores showed significant improvement from commencement to 3, 12 and 24 months (p<0.001).This descriptive study of prolotherapy in private practice has shown positive clinical outcomes for the 76% of patients who attended the 3-month follow-up visit (76% at 12 months and 32% at 24 months). Similar results were found in the questionnaires (Quebec Back Pain Disability Scale, Roland-Morris 24 and Roland-Morris 24 Multiform questionnaires) at 3, 12 and 24 months.
A 17-gene Assay to Predict Prostate Cancer Aggressiveness in the Context of Gleason Grade Heterogeneity, Tumor Multifocality, and Biopsy Undersampling
Authors: Eric A. Klein, Matthew R. Cooperberg, Cristina Magi-Galluzzi, Jeffry P. Simko, Sara M. Falzarano, Tara Maddala, June M. Chan, Jianbo Li, Janet E. Cowan, Athanasios C. Tsiatis, Diana B. Cherbavaz, Robert J. Pelham, Imelda Tenggara-Hunter, Frederick L. Baehner, Dejan Knezevic, Phillip G. Febbo, Steven Shak, Michael W. Kattan, Mark Lee, Peter R. Carroll
Journal: European Urology (2014)
Chronopharmacology: New Insights and Therapeutic Implications
Authors: Robert Dallmann, Steven A. Brown, Frédéric Gachon
Journal: The Annual Review of Pharmacology and Toxicology (2013)

Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug absorption or metabolism result in circadian pharmacokinetics, and oscillations in the physiological systems targeted by these drugs result in circadian pharmacodynamics. These clocks are present in most cells of the body, organized in a hierarchical fashion. Interestingly, some aspects of physiology and behavior are controlled directly via a "master clock" in the suprachiasmatic nuclei of the hypothalamus, whereas others are controlled by "slave" oscillators in separate brain regions or body tissues. Recent research shows that these clocks can respond to different cues and thereby show different phase relationships. Therefore, full prediction of chronopharmacology in pathological contexts will likely require a systems biology approach that considers chronointeractions among different clock-regulated systems.
Tuberculosis in AIDS: past or new problems?
Authors: C MAYAUD, J CADRANEL
Journal: Thorax (1999)

Since the emergence of AIDS, tuberculosis and HIV infection have been intimately connected. The immunodepression resulting from HIV infection increases the risk of tuberculosis progression in co-infected individuals and tuberculosis accelerates the course of HIV infection.1 In spite of new and effective anti-retroviral therapy, tuberculosis remains a major problem in HIV infected patients. In developing countries protease inhibitors containing anti-retroviral therapy are seldom used and tuberculosis remains the most common life threatening HIV related infection. A major goal in such a setting is to prevent and cure tuberculosis in HIV infected patients.2In developed countries protease inhibitors containing anti-retroviral therapy decrease the incidence of tuberculosis which, however, reveals HIV infection in some cases.3 In these countries the best strategy for treating tuberculosis and HIV infection together remains to be defined.

This editorial reviews the past, present, and future interactions between HIV infection and tuberculosis, focusing on their respective natural histories and treatments.

### IS TUBERCULOSIS MOST FREQUENT IN HIV INFECTED PATIENTS?

Several studies have clearly shown that the incidence of active tuberculosis is increased in HIV infected patients—for example, in two cohort studies of intravenous drug users4 5 the incidence of tuberculosis disease in patients with tuberculous infection defined by a positive PPD test was much higher in HIV seropositive than in HIV seronegative patients.

There is evidence that this increased incidence of tuberculosis disease in HIV infected patients results from three mechanisms: (1) reactivation of latent tuberculous infection which is suggested by the higher incidence of tuberculosis in HIV infected patients with a positive PPD test4; (2) rapid progression of recently acquired tuberculous infection which has been demonstrated by molecular epidemiology during several nosocomial outbreaks6; and (3) exogenous tuberculous reinfection which has also been shown by molecular analysis in patients with repeatedly positive cultures.7 

The incidence of tuberculosis is …
Is the Message Clear?
Authors: Arthur H. Rosen
Journal: JAMA (1977)

<h3>To the Editor.—</h3> In their letter to the editor, "Syrup of Ipecac: The Poison Retriever" (238:399, 1977), Greensher and Mofenson claim, "Identifying ipecac syrup as 'the poison retriever' in advertising and education campaigns should avoid its confusion with other dangerous products and lead to its greater availability." Though their attempt to educate is laudable, I believe that their solution fails to communicate to the intended audience. Educational research indicates that many Americans do not understand the written materials they come in contact with daily. For this reason, many industries have begun to rewrite their consumer literature so that it will be more readable for the general public. Unfortunately, what specialists in a given field consider more readable language often fails to meet the reading requirements of the general public. The phrase "poison retriever" on a bottle may confuse more people than it educates. A reader may infer that the contents
Complete Arterial Revascularization in Multivessel Coronary Artery Disease With 2 Conduits (Skeletonized Grafts and T Grafts)
Authors: O Wendler, B Hennen, S Demertzis, T Markwirth, D Tscholl, H Lausberg, Q Huang, L F Dübener, F Langer, H J Schäfers
Journal: Circulation (2000)

Complete arterial CABG is a surgical option to improve long-term results in the treatment of coronary artery disease (CAD). Harvesting of multiple arterial grafts is commonly associated with prolonged operating times and increased trauma. By use of new operative techniques (skeletonized grafts and the T-graft approach), CABG in multivessel CAD is now possible with only 2 grafts. We present our experience in the use of these techniques on a routine basis.Between March 1996 and September 1999, 490 patients (aged 61+/-9 years, 20% female) underwent complete arterial CABG. Left ventricular ejection fraction ranged from 15% to 85% (mean 59+/-15%). Triple-vessel disease was present in 88% of the patients. The incidence of diabetes mellitus was 32% (14% insulin dependent). Either both internal thoracic arteries (ITAs) (23%) or the left ITA and radial artery (77%) were used as conduits. In 85% of the patients, a T graft was created. Mean operating time was 198+/-46 minutes; bypass time, 82+/-25 minutes; and ischemic time, 58+/-22 minutes. Two to 7 (mean 4.1+/-0.9) anastomoses were performed per patient. Perioperative intra-aortic balloon pump was necessary in 12 patients (2.4%). The rate of perioperative myocardial infarction was 1.2%. Sternal complications occurred in 1. 0%, and in-hospital mortality was 2.2%. Postoperative coronary angiography in 172 patients (35%) documented excellent patency rates (left ITA 98.3%, right ITA 96.5%, and radial artery 96.6%).Complete arterial revascularization in multivessel CAD is possible with the use of only 2 grafts with good perioperative results. This approach allows for complete arterial CABG on a routine basis.
Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer
Authors: U. Veronesi, L. Mariani, A. Decensi, F. Formelli, T. Camerini, R. Miceli, M.G. Di Mauro, A. Costa, E. Marubini, M.B. Sporn, G. De Palo
Journal: Annals of Oncology (2006)
Inhibition of hepatitis B virus replication by targeted pretreatment of complexed antisense DNAin vitro
Authors: K Nakazono, Y Ito, C H Wu, G Y Wu
Journal: Hepatology (1996)

We have shown that antisense oligonucleotides can be targeted to hepatitis B virus (HBV)–infected cells, resulting in specific inhibition of viral protein synthesis and replication in vitro . The targeting system was based on the internalization of DNA complexes by highly selective receptors for galactose–terminal glycoproteins, asialoglycoproteins, on the surface of hepatocytes. Our objective in this study was to determine whether antisense DNA could be targeted to hepatocytes to prevent subsequent infection by HBV. A 21–mer phosphorothioate–linked oligo DNA complementary to the HBV polyadenylation signal and 5′–upstream sequences was complexed to a targetable DNA carrier consisting of asialoglycoprotein coupled to polylysine. Pretreatment of Huh7, asialoglycoprotein receptor (+) cells, with antisense complexes before lipofection with an HBV–plasmid at a level of 6.5 × 106 copies of plasmid per cell inhibited the amount of newly synthesized, core–associated viral DNA in Huh7 cells to undetectable levels, less than 0.1 pg, as assessed by quantitative polymerase chain reaction (PCR). Hepatitis B viral RNA transcripts were decreased by 60% compared with controls as detected by RNase protection assays, and HBV surface antigen (HBsAg) accumulation was inhibited by 97%. The inhibition lasted for 6 days and was dose dependent. Controls consisting of antisense alone and a random oligo complex showed no significant effect on any of the parameters under identical conditions. We conclude that preexposure of cells to targeted complexed antisense DNA can substantially block viral gene expression and viral replication after transfection of HBV DNA.
Selective accumulation of the X transcript of hepatitis B virus in patients negative for hepatitis B surface antigen with hepatocellular carcinoma
Authors: Patrizia Paterlini, Karine Poussin, Michael Kew, Dominique Franco, Christian Brechot
Journal: Hepatology (1995)

In HBsAg-negative patients with hepatocellular carcinoma (HCC), hepatitis B virus (HBV) genomes are present at a low copy number per cell, and the role of HBV in liver transformation is still unclear. We have mapped by polymerase chain reaction (PCR) the HBV genome in 19 HBsAg-negative tumorous and 9 corresponding nontumorous tissues and evaluated, by RT-PCR, the presence of HBV S, X, and C transcripts in the tumorous and nontumorous tissue of nine HBsAg-negative and, for comparison, six HBsAg-positive patients. Disrupted, presumably integrated, HBV genomes were detected by PCR in 10 of 19 tumorous tissues and in only one of nine nontumorous tissues. Significant accumulation of viral RNAs containing X but not C or S sequences was shown in 7/9 tumors and 7/8 nontumorous tissues from HBsAg-negative patients. In contrast, viral RNAs revealed by X-as well as by S- and C-specific primers were detected in five of six tumors and in six of six nontumorous tissues from HBsAg-positive patients. In conclusion, our results suggest the frequent integration of the HBV genome and the accumulation of X-related RNAs in HCCs developing in HBsAg-negative patients. This finding is consistent with a role, in these cases, for the potentially transforming X protein.
Cardiotrophin-1 Stimulation of Cardiac Fibroblast Growth
Authors: Toshihiro Tsuruda, Michihisa Jougasaki, Guido Boerrigter, Brenda K. Huntley, Horng H. Chen, Antonino B. D’Assoro, Shang C. Lee, Amy M. Larsen, Alessandro Cataliotti, John C. Burnett
Journal: Circulation Research (2002)

Cardiotrophin-1 (CT-1), a member of the interleukin-6 superfamily, and endothelin-1 (ET-1) are potent hypertrophic factors in cardiomyocytes. Although CT-1 and ET-1 gene expression in the heart is upregulated in experimental heart failure, their role in the activation of the cardiac fibroblast is unknown. This study was designed to identify the presence and action of CT-1 and its receptor complex, glycoprotein130 (gp130) and leukemia inhibitory factor (LIF) receptor, on cardiac fibroblast growth in cultured adult canine cardiac fibroblasts. In addition, we investigated the interaction between CT-1/gp130/LIF receptor and ET-1/endothelin type A (ET A ) receptor axis. Immunohistochemistry was performed using the indirect immunoperoxidase method, while we assessed the cell cycle of cardiac fibroblasts by flow cytometry, DNA synthesis by [ 3 H]thymidine incorporation, and collagen synthesis by [ 3 H]proline incorporation, respectively. CT-1 and gp130/LIF receptor were widely present in the cytoplasm of the cardiac fibroblasts. Exogenous CT-1 markedly stimulated [ 3 H]thymidine and [ 3 H]proline incorporations ( P &lt;0.01), with accumulation of cells in the S phase. Blockade of gp130 or LIF receptor inhibited basal growth as well as CT-1– or ET-1–stimulated cardiac fibroblast growth. The specific ET A receptor antagonist, BQ123, significantly inhibited CT-1–stimulated DNA synthesis. This study demonstrates that CT-1 and its receptors are present in cardiac fibroblasts. In addition, growth of these cells stimulated by endogenous and exogenous CT-1 requires gp130/LIF receptor as well as ET A receptor activation. We conclude that gp130/LIF receptor and ET A receptor activation are essential for cardiac fibroblast growth by CT-1 and that there is synergism with ET-1/ET A receptor axis.
Distribution and Functional Characterization of Equilibrative Nucleoside Transporter-4, a Novel Cardiac Adenosine Transporter Activated at Acidic pH
Authors: Kay Barnes, Halina Dobrzynski, Sophie Foppolo, Paul R. Beal, Fouzia Ismat, Elspeth R. Scullion, Lijie Sun, James Tellez, Mabel W.L. Ritzel, William C. Claycomb, Carol E. Cass, James D. Young, Rudi Billeter-Clark, Mark R. Boyett, Stephen A. Baldwin
Journal: Circulation Research (2006)

Adenosine plays multiple roles in the efficient functioning of the heart by regulating coronary blood flow, cardiac pacemaking, and contractility. Previous studies have implicated the equilibrative nucleoside transporter family member equilibrative nucleoside transporter-1 (ENT1) in the regulation of cardiac adenosine levels. We report here that a second member of this family, ENT4, is also abundant in the heart, in particular in the plasma membranes of ventricular myocytes and vascular endothelial cells but, unlike ENT1, is virtually absent from the sinoatrial and atrioventricular nodes. Originally described as a monoamine/organic cation transporter, we found that both human and mouse ENT4 exhibited a novel, pH-dependent adenosine transport activity optimal at acidic pH (apparent K(m) values 0.78 and 0.13 mmol/L, respectively, at pH 5.5) and absent at pH 7.4. In contrast, serotonin transport by ENT4 was relatively insensitive to pH. ENT4-mediated nucleoside transport was adenosine selective, sodium independent and only weakly inhibited by the classical inhibitors of equilibrative nucleoside transport, dipyridamole, dilazep, and nitrobenzylthioinosine. We hypothesize that ENT4, in addition to playing roles in cardiac serotonin transport, contributes to the regulation of extracellular adenosine concentrations, in particular under the acidotic conditions associated with ischemia.