tbuckley/cabot-search huggingface dataset:
The use of anti-tumour necrosis factor therapy in HIV-positive individuals with rheumatic disease
Authors: E J Cepeda, F M Williams, M L Ishimori, M H Weisman, J D Reveille
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> The purpose of this study was to examine the safety and efficacy of anti-tumour necrosis factor (TNF) agents (etanercept, infliximab and adalimumab) in HIV-positive patients with rheumatic diseases refractory to standard therapy. <h3>Methods:</h3> Patients were treated with anti-TNF blocker with rheumatic diseases refractory to disease modifying antirheumatic drugs who had a CD4 count of &gt;200 mm3 and an HIV viral load of &lt;60 000 copies/mm3 and no active concurrent infections. Changes in CD4 counts, HIV viral loads, or other adverse effects while on anti-TNF agents and clinical response were monitored for 28.1 (SD 20.9) months (range 2.5–55). <h3>Results:</h3> Eight HIV-positive patients were treated with anti-TNF blockers (two patients with rheumatoid arthritis, three with psoriatic arthritis, one with undifferentiated spondyloarthritis, one with reactive arthritis and one with ankylosing spondylitis). No significant clinical adverse effect was attributed to this treatment in any patient. CD4 counts and HIV viral load levels remained stable in all patients. Three patients on etanercept therapy and two patients on infliximab had sustained clinical improvement in their rheumatic diseases. <h3>Conclusions:</h3> This retrospective series of eight patients suggests that treatment with anti-TNF-α therapy is a viable alternative in HIV patients without advanced disease with associated rheumatic diseases refractory to standard therapy.
QUANTITATIVE RELATIONSHIPS IN THE SYSTEMATIC DESENSITIZATION OF PHOBIAS
Authors: JOSEPH WOLPE
Journal: American Journal of Psychiatry (1963)

Since it had been noted that in the desensitization treatment of phobias the number of presentations of a scene required to bring the anxiety level down to zero is not uniform but tends to increase or decrease on the way up a hierarchy, an attempt was made to establish quantitative relations by a study of those phobias that vary along a physical dimension. It was found that in claustrophobias and phobias in which anxiety rises with increasing proximity to a feared object the number of scene presentations to zero anxiety is low at a distance and increases with proximity, the cumulative curve corresponding to a positively accelerating function. In agoraphobias as in phobias increasing with number of objects the number of presentations needed is initially high and progressively falls as distance grows, the cumulative curve corresponding to a negatively accelerating function. In both cases the number of prestations to advance a segment of given size varies inversely with the distance of that segment from the central "safe zone" (as in agoraphobia) or "danger zone" (as in claustrophobia) in accordance with a simple power function such as has been constantly found to be the functional relation between stimulus magnitude and psychological magnitude.
Baculovirus capsid display: a novel tool for transduction imaging
Authors: Sari P. Kukkonen, Kari J. Airenne, Varpu Marjomäki, Olli H. Laitinen, Pauliina Lehtolainen, Pasi Kankaanpää, Anssi J. Mähönen, Jani K. Räty, Henri R. Nordlund, Christian Oker-Blom, Markku S. Kulomaa, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2003)

Baculoviruses are enveloped insect viruses that can carry large quantities of foreign DNA in their genome. Baculoviruses have proved to be very promising gene therapy vectors but little is known about their transduction mechanisms in mammalian cells. We show in this study that Autographa californica multiple nuclear polyhedrosis virus capsid is compatible with the incorporation of desired proteins in large quantities. Fusions can be made to the N-terminus or C-terminus of the major capsid protein vp39 without compromising the viral titer or functionality. As an example of the baculovirus capsid display we show a tracking of the baculovirus transduction in mammalian cells by an enhanced green fluorescent protein (EGFP)-displaying virus. Our confocal and electron microscopy results suggest that the transduction block in mammalian cells is not in the endosomal escape, as previously proposed, but rather in the cytoplasmic transport or nuclear entry of the virus capsid. Our results also suggest that the EGFP-tagged virus can be used for visualization of the virus biodistribution in vivo. Furthermore, capsid-modified baculoviruses hold great promise for the nuclear and subcellular targeting of transgenes and as a novel peptide display system for a variety of eukaryotic applications.
Population-based cancer survival trends in England and Wales up to 2007: an assessment of the NHS cancer plan for England
Authors: Bernard Rachet, Camille Maringe, Ula Nur, Manuela Quaresma, Anjali Shah, Laura M Woods, Libby Ellis, Sarah Walters, David Forman, John Steward, Michel P Coleman
Journal: The Lancet Oncology (2009)

BackgroundThe National Health Service (NHS) cancer plan for England was published in 2000, with the aim of improving the survival of patients with cancer. By contrast, a formal cancer strategy was not implemented in Wales until late 2006. National data on cancer patient survival in England and Wales up to 2007 thus offer the opportunity for a first formal assessment of the cancer plan in England, by comparing survival trends in England with those in Wales before, during, and after the implementation of the plan.MethodsWe analysed population-based survival in 2·2 million adults diagnosed with one of 21 common cancers in England and Wales during 1996–2006 and followed up to Dec 31, 2007. We defined three calendar periods: 1996–2000 (before the cancer plan), 2001–03 (initialisation), and 2004–06 (implementation). We estimated year-on-year trends in 1-year relative survival for patients diagnosed during each period, and changes in those trends between successive periods in England and separately in Wales. Changes between successive periods in mean survival up to 5 years after diagnosis were analysed by country and by government office region of England. Life tables for single year of age, sex, calendar year, deprivation category, and government office region were used to control for background mortality in all analyses.Findings1-year survival in England and Wales improved for most cancers in men and women diagnosed during 1996–2006 and followed until 2007, although not all trends were significant. Annual trends were generally higher in Wales than in England during 1996–2000 and 2001–03, but higher in England than in Wales during 2004–06. 1-year survival for patients diagnosed in 2006 was over 60% for 12 of 17 cancers in men and 13 of 18 cancers in women. Differences in 3-year survival trends between England and Wales were less marked than the differences in 1-year survival. North–South differences in survival trends for the four most common cancers were not striking, but the North West region and Wales showed the smallest improvements during 2001–03 and 2004–06.InterpretationThe findings indicate slightly faster improvement in 1-year survival in England than in Wales during 2004–06, whereas the opposite was true during 2001–03. This reversal of survival trends in 2001–03 and 2004–06 between England and Wales is much less obvious for 3-year survival. These different patterns of survival suggest some beneficial effect of the NHS cancer plan for England, although the data do not so far provide a definitive assessment of the effectiveness of the plan.FundingOffice for National Statistics (contract NT-04/2355A); Cancer Research UK (programme grant C1336/A5735).
Studies with Radioactive Gold
Authors: J. S. Lawrence
Journal: Annals of the Rheumatic Diseases (1961)

Although steroids, because of their more rapid action and ease of administration, have to some extent replaced gold compounds in the treatment of rheumatoid arthritis, there is evidence that, as regards both resistance to treatment and incidence of serious complications, gold compounds have the advantage (Kammerer and Cecil, 1958).The value of gold therapy has recently been confirmed by a double- blind trial (Empire Rheumatism Council, 1960).Minor complications are, however, frequent in patients treated with gold and may often necessitate interruptions in the course of treatment.It would, therefore, appear advantageous to obtain more information on the pharmacology and mode of action of these compounds and particularly on the mechanism by which patients become either resistant or hypersensitive to them.Except that patients receiving small doses are more likely to be resistant and that the frequency of sensitivity reactions is independent of total dosage, little is known of the factors involved (Ellman, Lawrence, and Thorold, 1940).Although chemical methods for the estimation of gold in blood and urine are available, these are technically difficult, and are of a degree of sensitivity which render the accurate assessment of the minute amounts occurring in the body fluids of patients under treatment with gold a matter of some un- certainty.Radioactive gold, on the other hand, can be estimated in amounts far below those found during therapy, and can, moreover, be detected in the tissues by scanning methods which enable the distribution throughout the body to be determined at frequent intervals after administration. Distribution and Concentration in Body FluidsThe distribution of administered gold in the tissues has been studied both in experimental animals and in man.In guinea-pigs, De Witt (1918) studied the concentration of gold after the administration of four organic gold compounds.The highest con- centration was found in the spleen with three of the * The cost of radioactive gold compounds for this investigation was covered by a grant from the Medical Research Council.four derivatives and in the lymph glands in the last.Lesser amounts were found in the liver, kidneys, and skin, and little elsewhere.In dogs, Eichel- 341
Effects of histamine acid phosphate and pentagastrin on gastric secretion in normal human subjects
Authors: D. A. Aubrey, A. P. M. Forrest
Journal: Gut (1970)

Six normal subjects were tested with various doses of histamine acid phosphate (1, 10, 40, and 80 μg/kg/hr) and pentagastrin (0·15, 1·5, 6·0, and 12·0 μg/kg/hr), the different doses of the stimulants being administered by separate continuous intravenous infusions. In each sample of gastric juice, which was collected at 15-minute intervals, we estimated the concentrations of the H<sup>+</sup>, Na<sup>+</sup>, K<sup>+</sup>, and Cl<sup>−</sup> and the concentration of pepsin. The drugs elicited equal maximal outputs of acid and pepsin. Pentagastrin was more potent than histamine in stimulating acid and pepsin secretion, and the rate of the responses was faster with pentagastrin than with histamine. Apart from this, however, the patterns of secretion of the various constituents of the gastric juice and the interrelationships between the concentrations of the electrolytes were identical with the two drugs. We therefore concluded that the actions of histamine acid phosphate and pentagastrin on human gastric secretion were identical.
Relative risks versus odds ratios
Authors: P. Sedgwick
Journal: BMJ (2014)

Researchers investigated the effectiveness of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use in hospital. A randomised double blind placebo controlled trial study design was used. The intervention consisted of the probiotic drink twice a day during a course of antibiotics and for one week afterwards. The control group received a placebo drink consisting of a longlife sterile milkshake. The primary outcome was the occurrence of antibiotic associated diarrhoea during follow-up.1 Participants were hospital patients aged over 50 years. In total, 135 patients were recruited to the trial and randomised to the intervention (n=69) or placebo (n=66). Twelve patients receiving the intervention and 10 in the placebo group did not complete their treatment protocol or were lost to follow-up. A smaller proportion of the probiotic group developed diarrhoea associated with antibiotic use compared with the placebo group (7 (12%) v 19 (34%); relative risk 0.36, 95% confidence interval 017 to 0.79). When adjusted using logistic regression to control for other factors, the effects of the probiotic drink in reducing antibiotic associated diarrhoea remained (odds ratio 0.25, 95% CI 0.07 to 0.85). The researchers concluded that consumption of the probiotic drink reduced the incidence of antibiotic associated diarrhoea. Which of the following statements, if any, are true?
PRO2000 vaginal gel for prevention of HIV-1 infection (Microbicides Development Programme 301): a phase 3, randomised, double-blind, parallel-group trial
Authors: Sheena McCormack, Gita Ramjee, Anatoli Kamali, Helen Rees, Angela M Crook, Mitzy Gafos, Ute Jentsch, Robert Pool, Maureen Chisembele, Saidi Kapiga, Richard Mutemwa, Andrew Vallely, Thesla Palanee, Yuki Sookrajh, Charles J Lacey, Janet Darbyshire, Heiner Grosskurth, Albert Profy, Andrew Nunn, Richard Hayes, Jonathan Weber
Journal: The Lancet (2010)
Smoking induces transcription of the heat shock protein system in the joints
Authors: Caroline Ospelt, Giovanni G Camici, Anna Engler, Christoph Kolling, Alexander Vogetseder, Renate E Gay, Beat A Michel, Steffen Gay
Journal: Annals of the Rheumatic Diseases (2014)

Smoking increases the risk of developing rheumatoid arthritis (RA) and worsens the course of the disease. In the current study we analysed whether smoking can affect gene expression directly in the joints.Synovial fibroblasts were incubated with 5% cigarette smoke extract and changes in gene expression were detected using whole genome microarrays and verified with real-time PCR. Synovial tissues were obtained from smoking and non-smoking patients with RA undergoing joint replacement surgery and from mice exposed to cigarette smoke or ambient air in a whole body exposure chamber for 3 weeks.Microarray and real-time PCR analysis showed a significant upregulation of the heat shock proteins DnaJA4, DnaJB4, DnaJC6, HspB8 and Hsp70 after stimulation of synovial fibroblasts with 5% cigarette smoke extract. Similarly, in synovial tissues of smokers with RA the expression of DnaJB4, DnaJC6, HspB8 and Hsp70 was significantly higher compared with non-smokers with RA. Upregulation of DnaJB4 and DnaJC6 in joints by smoking was also confirmed in mice exposed to cigarette smoke.Our data clearly show that smoking can change gene expression in the joints, which can lead to the activation of signalling pathways that promote development of autoimmunity and chronic joint inflammation.
Autonomous Maturation of α/β T Lineage Cells in the Absence of Cooh-Terminal Src Kinase (Csk)
Authors: Christian Schmedt, Alexander Tarakhovsky
Journal: The Journal of Experimental Medicine (2001)

The deletion of COOH-terminal Src kinase (Csk), a negative regulator of Src family protein tyrosine kinases (PTKs), in immature thymocytes results in the development of α/β T lineage cells in T cell receptor (TCR) β-deficient or recombination activating gene (rag)-1–deficient mice. The function of Csk as a repressor of Lck and Fyn activity suggests activation of these PTKs is solely responsible for the phenotype observed in csk-deficient T lineage cells. We provide genetic evidence for this notion as α/β T cell development is blocked in lck−/−fyn−/− csk-deficient mice. It remains unclear whether activation of Lck and Fyn in the absence of Csk uncouples α/β T cell development entirely from engagement of surface-expressed receptors. We show that in mice expressing the α/β TCR on csk-deficient thymocytes, positive selection is biased towards the CD4 lineage and does not require the presence of major histocompatibility complex (MHC) class I and II. Furthermore, the introduction of an MHC class I–restricted transgenic TCR into a csk-deficient background results in the development of mainly CD4 T cells carrying the transgenic TCR both in selecting and nonselecting MHC background. Thus, TCR–MHC interactions have no impact on positive selection and commitment to the CD4 lineage in the absence of Csk. However, TCR-mediated negative selection of csk-deficient, TCR transgenic cells is normal. These data suggest a differential involvement of the Csk-mediated regulation of Src family PTKs in positive and negative selection of developing thymocytes.
Association between the IL6-174G/C SNP and maximally attained lung function
Authors: B. van den Borst, N. Y. Souren, M. Gielen, R. J. F. Loos, A. D. C. Paulussen, C. Derom, A. M. W. J. Schols, M. P. A. Zeegers
Journal: Thorax (2010)

Recently, He et al 1 reported that the C allele of the interleukin 6 ( IL6 )-174G/C promoter polymorphism was associated with a rapid decline in forced expiratory volume in 1 s (FEV1) (≥3% predicted/year) and susceptibility to chronic obstructive pulmonary disease (COPD) in middle-aged smokers derived from three different cohorts.1 Alternatively, as also suggested by He et al in their discussion,1 we hypothesised that the IL6 -174G/C single nucleotide polymorphism (SNP) might not only affect the rate of lung function decline but also …
Instant Power Spectrum Analysis of Heart Rate Variability During Orthostatic Tilt Using a Time-/Frequency-Domain Method
Authors: Sylvain Jasson, Claire Médigue, Pierre Maison-Blanche, Nicola Montano, Laurent Meyer, Christophe Vermeiren, Pascale Mansier, Philippe Coumel, Alberto Malliani, Bernard Swynghedauw
Journal: Circulation (1997)

Background Spectral analysis of heart rate (HR) variability (HRV) requires, as a rule, some level of stationarity and, as a result, is inadequate to quantify biological transients. A time-/frequency-domain method (TF) was developed to obtain an instant spectral power (SP) of HRV during tilt. Methods and Results HR was recorded by Holter monitoring in volunteers and analyzed with a TF, the smoothed pseudo–Wigner-Ville transformation (SPWVT), with the table inclination randomly set or continuously increased while the table rotated in head-up position. (1) The SPWVT assesses, beat by beat, the instant center frequency (ICF) of the SP. ICF correlates better with instant HR than the ratio of low- (LF) to high-frequency (HF) oscillations. The transient effect of tilt is better characterized as a shift of SP toward lower frequencies than by changes in amplitudes. (2) The method evidences variations of HR from one second to another. During the passage to head-up position, the vagal withdrawal and the sympathetic activation occur nearly simultaneously, as indicated by the instant changes in both LF and HF amplitudes and ICF. (3) The averaged results of the SPWVT give results similar to those previously obtained with autoregressive algorithms. Conclusions The SPWVT is a new tool to explore HR transitions such as periods before episodes of arrhythmias on a time scale of one beat and allows quantification of an instant frequency index (ICF) that closely reflects the instantaneous relationship between sympathetic and vagal modulations.
Neural reflexes in inflammation and immunity
Authors: Ulf Andersson, Kevin J. Tracey
Journal: The Journal of Experimental Medicine (2012)

The mammalian immune system and the nervous system coevolved under the influence of infection and sterile injury. Knowledge of homeostatic mechanisms by which the nervous system controls organ function was originally applied to the cardiovascular, gastrointestinal, musculoskeletal, and other body systems. Development of advanced neurophysiological and immunological techniques recently enabled the study of reflex neural circuits that maintain immunological homeostasis, and are essential for health in mammals. Such reflexes are evolutionarily ancient, dating back to invertebrate nematode worms that possess primitive immune and nervous systems. Failure of these reflex mechanisms in mammals contributes to nonresolving inflammation and disease. It is also possible to target these neural pathways using electrical nerve stimulators and pharmacological agents to hasten the resolution of inflammation and provide therapeutic benefit.
Pulmonary alveolar proteinosis due to a novel mutation in CSF2RA
Authors: C. Happle, M. Wetzke, A.M. Dittrich, G. Hansen, N. Schwerk
Journal: European Respiratory Journal (2012)

Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by pulmonary accumulation of surfactant protein. Congenital forms can result from mutations in granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, leading to a terminal differentiation block of alveolar macrophages.

We present the case of a 3yr-old girl born to consanguineous parents presenting with progressive dyspnoea, cough and failure to thrive. Her arterial oxygen saturation was 80% while breathing ambient air and dropped to 50% during agitation. Chest radiographs showed bilateral opacities, and high-resolution computed tomography (CT) revealed interlobular densification with typical “crazy paving” pattern. Due to a milky, opaque appearance of bronchioalveolar lavage fluid (BALF) and a strongly PAS-positive staining in histology, the diagnosis of PAP was suspected. After whole lung lavage (WLL), significant clinical improvement occurred. Oxygen saturation increased to >90% and follow-up chest radiographs showed partial clearance.

Currently, the patient is undergoing WLL every 4-6 weeks. After 10 months of treatment, she has gained 9 kg of weight, visits kindergarten, and has a good quality of life.

The patient's serum- and BALF- GM-CSF concentrations were significantly elevated. Functional analyses of neutrophils and monocytes showed significantly reduced GM-CSF responsiveness. Sequencing revealed a novel mutation in exon seven of the GM-CSF receptor alpha chain gene (CSF2RA). Regarding long-term perspectives, hematopoietic stem cell transplantation (HSCT) has to be considered. However, only one case HSCT in paediatric PAP has been described, with fatal outcome due to a transplantation-associated infection.
Beautiful minds (i.e., brains) and the neural basis of intelligence
Authors: Richard J. Haier, Rex E. Jung
Journal: Behavioral and Brain Sciences (2007)

Abstract The commentaries address conceptual issues ranging from our narrow focus on neuroimaging to the various definitions of intelligence. The integration of the P-FIT and data from cognitive neuroscience is particularly important and considerable consistency is found. Overall, the commentaries affirm that advances in neuroscience techniques have caused intelligence research to enter a new phase. The P-FIT is recognized as a reasonable empirical framework to test hypotheses about the relationship of brain structure and function with intelligence and reasoning.