tbuckley/cabot-search huggingface dataset:
Tuberculosis and its future management
Authors: J. C Moore-Gillon
Journal: Thorax (2007)

Will we do better in the next 25 years?

Twenty-five years ago, most writers on tuberculosis (TB) would, if asked to predict what the position would be by 2007, have anticipated better diagnostics, safer drugs, shorter treatment times, a better vaccine, the near eradication of TB in the developed world and falling rates in the developing world. Some perceptive individuals were sounding the warning bells, but most pundits would have been profoundly wrong. They would have been closest to the mark if they had simply summed up their prediction of the position 25 years later, in 2007, as “Much the same, really—except where it’s much worse.”

Predictions about TB are particularly fraught with difficulty because the impact of factors beyond the control of clinicians, researchers and the pharmaceutical industry is far greater with TB than it is in diseases like asthma, chronic obstructive pulmonary disease and lung cancer. These views on TB and its future management are therefore contingent upon three assumptions—all, some or none of which may come to pass: a modest increase in overall global prosperity, wars and political instability being at least no worse than they are at present, and the development of a reasonably effective AIDS vaccine. We can be completely confident of only one thing: 25 years from now, the December 2032 issue of Thorax (whether on paper or not) will reproduce these December 2007 editorials with a commentary on the extent to which I (and my co-authors) got it wrong.

The Stop TB partnership, coordinated by the World Health Organisation, has set out the actions—and the funds—needed for TB control.1 Targets include the halving, by 2015, of TB prevalence and deaths compared with 1990 levels, and the elimination of TB as a global public health problem by 2050. Progress in vaccines, …
Nitinol Self-Expanding Stents: When Severe Twisting Occurs, Self-Expansion May Ensue After a Waiting Period
Authors: J. P. Chung, H. J. Park, K. S. Lee, J. B. Chung, C. Y. Chon, J. K. Kang, I. S. Park
Journal: Endoscopy (1997)

One of the major disadvantages of nitinol endocoil stents is said to be incomplete deployment leading to twisting and stent dysfunction. We report a patient with irresectable pancreatic head cancer where severe twisting of the nitinol stent occurred which resolved on the day after stent insertion; the stent took its normal shape ten days later, whereafter the patient lived without stent-related problems for one year until his death. This shows that prospective management rather than immediate stent extraction may be warranted in such cases of stent dysfunction.
Domain Tree-Based Analysis of Protein Architecture Evolution
Authors: K. Forslund, A. Henricson, V. Hollich, E. L. L. Sonnhammer
Journal: Molecular Biology and Evolution (2007)

Understanding the dynamics behind domain architecture evolution is of great importance to unravel the functions of proteins. Complex architectures have been created throughout evolution by rearrangement and duplication events. An interesting question is how many times a particular architecture has been created, a form of convergent evolution or domain architecture reinvention. Previous studies have approached this issue by comparing architectures found in different species. We wanted to achieve a finer-grained analysis by reconstructing protein architectures on complete domain trees. The prevalence of domain architecture reinvention in 96 genomes was investigated with a novel domain tree–based method that uses maximum parsimony for inferring ancestral protein architectures. Domain architectures were taken from Pfam. To ensure robustness, we applied the method to bootstrap trees and only considered results with strong statistical support. We detected multiple origins for 12.4% of the scored architectures. In a much smaller data set, the subset of completely domain-assigned proteins, the figure was 5.6%. These results indicate that domain architecture reinvention is a much more common phenomenon than previously thought. We also determined which domains are most frequent in multiply created architectures and assessed whether specific functions could be attributed to them. However, no strong functional bias was found in architectures with multiple origins.
High CD46 Receptor Density Determines Preferential Killing of Tumor Cells by Oncolytic Measles Virus
Authors: Bambi D. Anderson, Takafumi Nakamura, Stephen J. Russell, Kah-Whye Peng
Journal: Cancer Research (2004)

Abstract Live attenuated Edmonston B strain of measles virus (MV-Edm) is a potent and specific oncolytic agent, but the mechanism underlying its tumor selectivity is unknown. The virus causes cytopathic effects (CPEs) of extensive syncytial formation in tumor cells but minimal damage or cell killing in normal cells. The CPE is dependent on expression of viral proteins and the presence of CD46, the major cellular receptor of MV-Edm. Using a virally encoded soluble marker peptide to provide a quantitative readout of the level of viral gene expression, we determined that tumor cells and normal cells expressed comparable levels of viral proteins. CD46 mediates virus attachment, entry, and virus-induced cell-to-cell fusion. Using engineered cells expressing a range of CD46 densities, we determined that whereas virus entry increased progressively with CD46 density, cell fusion was minimal at low receptor densities but increased dramatically above a threshold density of CD46 receptors. It is well established that tumor cells express abundant CD46 receptors on their surfaces compared with their normal counterparts. Thus, at low CD46 densities typical of normal cells, infection occurs, but intercellular fusion is negligible. At higher densities typical of tumor cells, infection leads to extensive cell fusion. Intercellular fusion also results in enhancement of viral gene expression through recruitment of neighboring uninfected cells into the syncytium, further amplifying the CPE. Discrimination between high and low CD46 receptor density provides a compelling basis for the oncolytic specificity of MV-Edm and establishes MV-Edm as a promising CD46-targeted cancer therapeutic agent.
Generalized pustular psoriasis successfully treated with topical tacrolimus
Authors: F. Rodriguez Garcia, E. Fagundo Gonzalez, R. Cabrera-Paz, M. Rodriguez Martin, M. Saez Rodriguez, F. Martin-Neda, M. Garcia Bustinduy, A. Noda Cabrera, R. Sanchez Gonzalez
Journal: British Journal of Dermatology (2005)

Journal Article Generalized pustular psoriasis successfully treated with topical tacrolimus Get access F. Rodríguez García, F. Rodríguez García Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar E. Fagundo González, E. Fagundo González Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R. Cabrera‐Paz, R. Cabrera‐Paz Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M. Rodriguez Martín, M. Rodriguez Martín Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M. Sáez Rodríguez, M. Sáez Rodríguez Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar F. Martín‐Neda, F. Martín‐Neda Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar M. García Bustinduy, M. García Bustinduy Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar A. Noda Cabrera, A. Noda Cabrera Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar R. Sánchez González R. Sánchez González Servicio de Dermatología, Hospital Universitario de Canarias, S/C de Tenerife, Spain E‐mail: fm_derma@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 152, Issue 3, 1 March 2005, Pages 587–588, https://doi.org/10.1111/j.1365-2133.2005.06468.x Published: 01 March 2005
SearCh for humourIstic and Extravagant acroNyms and Thoroughly Inappropriate names For Important Clinical trials (SCIENTIFIC): qualitative and quantitative systematic study
Authors: A. Pottegard, M. B. Haastrup, T. B. Stage, M. R. Hansen, K. S. Larsen, P. M. Meegaard, L. H. V. Meegaard, H. Horneberg, C. Gils, D. Dideriksen, L. Aagaard, A. B. Almarsdottir, J. Hallas, P. Damkier
Journal: BMJ (2014)

<b>Objectives</b> To describe the development of acronym use across five major medical specialties and to evaluate the technical and aesthetic quality of the acronyms. <b>Design</b> Acronyms obtained through a literature search of Pubmed.gov followed by a standardised assessment of acronym quality (BEAUTY and CHEATING criteria). <b>Participants</b> Randomised controlled trials within psychiatry, rheumatology, pulmonary medicine, endocrinology, and cardiology published between 2000 and 2012. <b>Main outcome measures</b> Prevalence proportion of acronyms and composite quality score for acronyms over time. <b>Results</b> 14 965 publications were identified, of which 18.3% (n=2737) contained an acronym in the title. Acronym use was more common among cardiological studies than among the other four medical specialties (40% <i>v</i> 8-15% in 2012, P&lt;0.001). Except for within cardiology, the prevalence of acronyms increased over time, with the average prevalence proportion among the remaining four specialties increasing from 4.0% to 12.4% from 2000 to 2012 (P&lt;0.001). The median combined acronym quality score decreased significantly over the study period (P&lt;0.001), from a median 9.25 in 2000 to 5.50 in 2012. <b>Conclusion</b> From 2000 to 2012 the prevalence of acronyms in trial reports increased, coinciding with a substantial decrease in the technical and aesthetic quality of the acronyms. Strict enforcement of current guidelines on acronym construction by journal editors is necessary to ensure the proper use of acronyms in the future.
Exhaled nitric oxide in cystic fibrosis: relationships with airway and lung vascular impairments
Authors: D. Hubert, F. Aubourg, B. Fauroux, L. Trinquart, I. Sermet, G. Lenoir, A. Clément, A. T. Dinh-Xuan, B. Louis, B. Mahut, C. Delclaux
Journal: European Respiratory Journal (2009)

A reduction of exhaled nitric oxide (NO) fraction and endothelial-mediated dysfunction have been reported in cystic fibrosis (CF). The aims of the present study were to search for relationships between flow-independent NO exchange parameters (bronchial NO flux ( J ′ aw,NO ) and alveolar NO concentration ( C A,NO )) and lung function tests characterising airflow limitation and pulmonary vascular bed (capillary blood volume and physiological dead space/tidal volume ( V D / V T ) ratio on exercise). In total, 34 patients (16 children, 18 adults) with CF, without resting pulmonary hypertension, underwent spirometry, exhaled NO measurement (multiple constant flow analytical method), gas transfer assessment (carbon monoxide and NO, allowing the calculation of capillary volume and membrane conductance) and a graded exercise test with oxygen uptake ( V ′ O 2 ), carbon dioxide production ( V ′ CO 2 ) and arterial blood gas evaluations. Both J ′ aw,NO and C A,NO correlated positively with airflow limitation. C A,NO correlated positively with capillary/alveolar volume. During exercise, criteria of mild pulmonary vascular disease were evidenced in some patients that participated in exercise limitation (negative correlation between physiological V D / V T and peak V ′ O 2 ). C A,NO at rest correlated positively with these parameters of wasted ventilation during exercise (physiological V D / V T , minute ventilation ( V ′ E )/ V ′ CO 2 at ventilatory threshold and V ′ E / V ′ CO 2 slope). Flow-independent exhaled NO parameters are linked to airway and early vascular diseases in patients with CF.
Predisposition to Vasovagal Syncope in Subjects With Blood/Injury Phobia
Authors: Valentina Accurso, Mikolaj Winnicki, Abu S.M. Shamsuzzaman, Amy Wenzel, Alan Kim Johnson, Virend K. Somers
Journal: Circulation (2001)

Background — Most subjects with blood/injury phobia experience syncope or presyncope as part of the phobic response. We tested the hypothesis that these subjects have a constitutional autonomic dysregulation that predisposes them to vasovagal syncope during head-up tilt. Methods and Results — We studied 11 subjects (9 females, 2 males) who had a history of syncope or presyncope only in response to a blood or injury stimulus and 11 healthy matched controls (10 females, 1 male) without a history of syncope. Blood pressure (BP) and heart rate (HR) were measured during a 15-minute baseline period with subjects in the supine position and then during 45 minutes of head-up tilt to 70°. Measurements at rest did not differ between the blood phobic and control subjects. During tilt, 9 (82%) of the 11 blood phobic subjects experienced presyncope or syncope, leading to termination of the study after 22±17 minutes of tilt. Only 1 (9%) of the 11 control subjects experienced presyncope (χ 2 =11.7, P =0.001). Hemodynamic responses to tilt were consistent with a vasovagal mechanism in the blood phobic subjects, with simultaneous decreases in BP and HR during tilt. During tilt, systolic BP fell by 21±15 mm Hg ( P =0.001), and HR fell by 22±25 bpm ( P =0.01). By contrast, BP and HR were very stable in the control group. Conclusions — Subjects with syncope related to blood/injury phobia have an underlying autonomic dysregulation predisposing them to neurally mediated syncope, even in the absence of any blood or injury stimulus. Fainting related to these stimuli may in large part be due to dysfunction in neural circulatory control, which may secondarily lead to the phobia because of repeated syncopal events.
Preclinical Evidence That PD1 Blockade Cooperates with Cancer Vaccine TEGVAX to Elicit Regression of Established Tumors
Authors: Juan Fu, Ian-James Malm, Deepak K. Kadayakkara, Hy Levitsky, Drew Pardoll, Young J. Kim
Journal: Cancer Research (2014)

Biomarker studies have shown that expression of the T-cell coregulatory ligand PDL1 on tumor cells correlates with clinical responsiveness to the PD1 antibody nivolumab. Here, we report the findings of a preclinical cancer vaccine study demonstrating vaccine-dependent PDL1 upregulation in the tumor microenvironment. We formulated an IFNγ-inducing cancer vaccine called TEGVAX that combined GM-CSF and multiple Toll-like receptor agonists to increase the number of activated dendritic cells. Treatment of established tumors with TEGVAX retarded tumor growth in a manner associated with enhanced systemic antitumor immunity. Unexpectedly, TEGVAX also upregulated PDL1 expression in the tumor microenvironment, possibly explaining why tumors were not eliminated completely. In support of this likelihood, PDL1 upregulation in this setting relied upon IFNγ-expressing tumor-infiltrating CD4(+) and CD8(+) T cells and administration of a PD1-blocking antibody with TEGVAX elicited complete regression of established tumors. Taken together, our findings provide a mechanistic rationale to combine IFNγ-inducing cancer vaccines with immune checkpoint blockade.
Induction chemotherapy with capecitabine and oxaliplatin followed by chemoradiotherapy before total mesorectal excision in patients with locally advanced rectal cancer
Authors: J V Schou, F O Larsen, L Rasch, D Linnemann, J Langhoff, E Høgdall, D L Nielsen, K Vistisen, A Fromm, B V Jensen
Journal: Annals of Oncology (2012)
Serum concentrations of soluble P-selectin glycoprotein ligand-1 are increased in patients with systemic sclerosis: association with lower frequency of pulmonary fibrosis
Authors: K Yanaba
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine serum concentrations of soluble P-selectin glycoprotein ligand-1 (sPSGL-1) and its clinical associations in patients with systemic sclerosis. <b>Methods:</b> Serum sPSGL-1 concentrations from 65 patients with systemic sclerosis were examined by enzyme linked immunosorbent assay. In a retrospective longitudinal study, 177 sera from 35 patients with systemic sclerosis were analysed (follow up 0.3 to 6.3 years) <b>Results:</b> Serum sPSGL-1 was raised in patients with limited cutaneous systemic sclerosis (lSSc) (n = 34) and diffuse cutaneous systemic sclerosis (dSSc) (n = 31) compared with healthy controls (n = 22) and patients with systemic lupus erythematosus (n = 20) or dermatomyositis (n = 20). Patients with systemic sclerosis who had raised sPSGL-1 concentrations less often had pulmonary fibrosis and decreased vital capacity (%VC) than those with normal sPSGL-1 levels. sPSGL-1 concentrations were positively correlated with %VC in patients with systemic sclerosis. In the longitudinal study, patients with systemic sclerosis but without pulmonary fibrosis had consistently increased sPSGL-1 concentrations in the early phase, while those with pulmonary fibrosis had decreased sPSGL-1 throughout the follow up period. <b>Conclusions:</b> A raised serum sPSGL-1 is associated with a lower frequency and severity of pulmonary fibrosis in systemic sclerosis. sPSGL-1 could be a protective factor against the development of pulmonary fibrosis in this disease and as such would be a possible therapeutic target.
Enhanced B Cell Expansion, Survival, and Humoral Responses by Targeting Death Receptor 6
Authors: Clint S. Schmidt, Jinqi Liu, Tonghai Zhang, Ho Yeong Song, George Sandusky, Karen Mintze, Robert J. Benschop, Andrew Glasebrook, Derek D. Yang, Songqing Na
Journal: The Journal of Experimental Medicine (2002)

Targeted disruption of death receptor (DR)6 results in enhanced CD4(+) T cell expansion and T helper cell type 2 differentiation after stimulation. Similar to T cells, DR6 is expressed on resting B cells but is down-regulated upon activation. We examined DR6(-/-) B cell responses both in vitro and in vivo. In vitro, DR6(-/-) B cells undergo increased proliferation in response to anti-immunoglobulin M, anti-CD40, and lipopolysaccharide. This hyperproliferative response was due, at least in part, to both increased cell division and reduced cell apoptosis when compared with wild-type B cells. Consistent with these observations, increased nuclear levels and activity of nuclear factor kappaB transcription factor, c-Rel, and elevated Bcl-x(l) expression were observed in DR6(-/-) B cells upon stimulation. In addition, DR6(-/-) B cells exhibited higher surface levels of CD86 upon activation and were more effective as antigen-presenting cells in an allogeneic T cell proliferation response. DR6(-/-) mice exhibited enhanced germinal center formation and increased titers of immunoglobulins to T-dependent as well as T-independent type I and II antigens. This is the first demonstration of a regulatory role of DR6 in the activation and function of B cells.
Effects of fasting and refeeding on somatostatin concentration and binding to cytosol from rabbit gastric mucosa.
Authors: B Roca, R Fernandez-Valencia, E Arilla
Journal: Gut (1988)

Somatostatin like immunoreactivity and the density of somatostatin binding sites were measured in stomach (fundus and antrum) from either fed, 12 to 96 hours fasted, or 96 hours fasted plus 48 hours refed rabbits. The somatostatin concentration increased in fundic and antral mucosa after 24 h and reached its highest value after 96 h of fasting. The number of specific somatostatin binding sites with high and low affinity decreased with the duration of fasting. Refeeding of fasted animals resulted in a normalisation to control values of gastric mucosal somatostatin and somatostatin binding.
Importance of the Vasoactive Intestinal Peptide Receptor in the Stimulation of Cyclic Adenosine 3′,5′-Monophosphate in Gallbladder Epithelial Cells of Man
Authors: Christophe Dupont, Jean-Pierre Broyart, Yvonne Broer, Bernard Chenut, Marc Laburthe, Gabriel Rosselin
Journal: Journal of Clinical Investigation (1981)

An EDTA procedure was used to prepare isolated epithelial cells of human gallbladder devoid of endogenous vasoactive intestinal peptide (VIP) as measured by radioimmunoassay. Specific binding sites for VIP were characterized in these cells. At 37°C, the binding of 125I-labeled VIP reached a peak within 20 min and then declined rapidly. At 15°C, binding was stable between 90 and 180 min of incubation. Binding of the labeled peptide was inhibited by concentrations of native VIP of 30 pM-0.1 μM. Half-maximal inhibition was observed at 2 nM. Scatchard analysis indicated two functionally independent classes of receptor sites: 62,000 high affinity sites/cell with a dissociation constant (Kd) of 1.3 nM, and 510,000 low affinity sites/cell with a Kd of 16.2 nM. Secretin inhibited tracer binding but with a 1,000 times lower potency than native VIP. VIP strongly stimulated adenosine 3′:5′ monophosphate (cyclic AMP) production in human gallbladder epithelial cells. At 37°C, 0.1 nM and 10 nM VIP raised cyclic AMP levels 44 and 100 times above the basal level, respectively. Maximal values remained constant between 60 and 90 min at 15°C. The importance of the VIP-induced cyclic AMP rise was related, at least in part, to a low phosphodiesterase activity in human gallbladder epithelial cells. At equilibrium, during a 60-min incubation at 15°C, cyclic AMP production was noted at concentrations of VIP as low as 3 pM. Maximal and half-maximal stimulations were observed at 10 nM and 0.2 nM VIP, respectively. Secretin also stimulated cyclic AMP production but with a 10,000 lower potency than VIP.
Regulation of mTOR by Phosphatidic Acid?
Authors: David A. Foster
Journal: Cancer Research (2007)

Interest in the regulation of the mammalian target of rapamycin (mTOR) has increased substantially in recent years largely because of an apparent link between mTOR and survival signals in human cancer cells. Much has been learned about the regulation of mTOR in response to survival signals generated by phosphatidylinositol 3-kinase (PI3K). However, another mechanism for regulating mTOR has been proposed involving the generation of phosphatidic acid (PA). PA is the metabolic product of phospholipase D (PLD), whose activity is elevated in a large number of human cancers, and, like PI3K, has been implicated in the survival of human cancer cells. Although the regulation of mTOR by the PI3K signaling pathway is well established, a role for PLD and PA in regulating mTOR has been controversial. In this review, the evidence implicating PLD and PA in the regulation of mTOR is summarized, and the implications of this novel and potentially important mechanism for regulating mTOR are discussed.
MATERNAL AND INFANT ANTIBODY RESPONSE TO MENINGOCOCCAL VACCINATION IN PREGNANCY
Authors: Azarias De Andrade Carvalho, CARMENMARIAS Giampaglia, Harue Kimura, OCTAVIOAUGUSTODEC Pereira, Calil Kairalla Farhat, José Carlos Neves, Renato Prandini, Eduardo Da Silva Carvalho, Antonio Miguel Zarvos
Journal: The Lancet (1977)