tbuckley/cabot-search huggingface dataset:
An Address on the Surgery of the Tongue
Authors: J. Hutchinson
Journal: BMJ (1891)

T cells from patients with systemic lupus erythematosus exhibit a notable array of defects that probably contribute to the origin and development of the disease. Such abnormalities include an abnormal response to stimulation, aberrant expression of molecules that play key roles in intracellular signalling pathways, altered transcription factor activation and binding, and skewed gene expression. The combination of these alterations leads the cell to the expression of a particular phenotype that intense research has gradually uncovered over the last years. The aim of this article is to review the findings that have allowed us to better understand the behaviour of the lupus T cell and highlight the molecules that represent potential therapeutic targets.
Diagnostic value of the Manning criteria in irritable bowel syndrome.
Authors: N J Talley, S F Phillips, L J Melton, C Mulvihill, C Wiltgen, A R Zinsmeister
Journal: Gut (1990)

Because unexplained 9functional symptoms9 are a major cause of referral to gastroenterologists, the efficiency of the medical history to lead to a positive diagnosis of irritable bowel syndrome, without resorting to the use of expensive tests, remains a key question. Whilst the six criteria of Manning et al are widely used, data on their validity in discriminating irritable bowel syndrome from healthy controls, irritable bowel syndrome from non-ulcer dyspepsia and especially among irritable bowel syndrome subgroups, are not available. To evaluate this, we studied 361 outpatients who completed a bowel disease questionnaire, which objectively measured Manning9s (and other) criteria. The group included 82 patients with irritable bowel syndrome, 33 with non-ulcer dyspepsia, 101 with organic gastrointestinal disease, and 145 healthy controls. Diagnoses were based on a full and independent clinical evaluation, not on responses to the bowel disease questionnaire. Reliability was assessed by a test-retest procedure. All six of the individual Manning criteria were found to be reliable (median kappa = 0.79). Based on a logistic regression analysis of the discriminatory value of Manning9s criteria, as the number of positive criteria increased, so did the predicted probability of irritable bowel syndrome. This predictive value was highest in younger patients and in females. The Manning criteria discriminated irritable bowel syndrome from organic gastrointestinal disease and from all non-irritable bowel syndrome gastrointestinal disease with a sensitivity of 58% and 42%, and a specificity of 74% and 85%, respectively. Stools that were often loose and watery provided an additional independent criterion for distinguishing irritable bowel syndrome from non-irritable bowel syndrome. Thus, symptoms can be used to diagnose irritable bowel syndrome positively, but Manning9s criteria are not highly sensitive.
A systematic review of the clinical effectiveness of first-line chemotherapy for adult patients with locally advanced or metastatic non-small cell lung cancer
Authors: G. Pilkington, A. Boland, T. Brown, J. Oyee, A. Bagust, R. Dickson
Journal: Thorax (2015)

Our aim was to evaluate the clinical effectiveness of chemotherapy treatments currently licensed in Europe and recommended by the National Institute for Health and Care Excellence (NICE) for the first-line treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). A systematic search of MEDLINE, EMBASE and the Cochrane Library for randomised controlled trials (RCTs) published from 2001 to 2010 was carried out. Relative treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using standard meta-analysis and mixed treatment comparison methodology. A total of 23 RCTs were included: 18 trials compared platinum-based chemotherapy, two compared pemetrexed and three compared gefitinib. There are no statistically significant differences in OS between any of the four third-generation chemotherapy regimens. There is statistically significant evidence that pemetrexed+platinum increases OS compared with gemcitabine+platinum. There are no statistically significant differences in OS between gefitinib and docetaxel+platinum or between gefitinib and paclitaxel+platinum. There is a statistically significant improvement in PFS with gefitinib compared with docetaxel+platinum and gefitinib compared with paclitaxel+platinum. Due to reduced generic pricing, third-generation chemotherapy regimens (except vinorelbine) are still competitive options for most patients. This research provides a comprehensive evidence base, which clinicians and decision-makers can use when deciding on the optimal first-line chemotherapy treatment regimen for patients diagnosed with locally advanced or metastatic NSCLC.
[11C]Choline Positron Emission Tomography in Estrogen Receptor–Positive Breast Cancer
Authors: Kaiyumars B. Contractor, Laura M. Kenny, Justin Stebbing, Adil Al-Nahhas, Carlo Palmieri, Dudley Sinnett, Jacqueline S. Lewis, Katy Hogben, Safiye Osman, Sami Shousha, Charles Lowdell, R. Charles Coombes, Eric O. Aboagye
Journal: Clinical Cancer Research (2009)

Abstract Purpose: Novel radiotracers could potentially allow the identification of clinically aggressive tumor phenotypes. As choline metabolism increases during malignant transformation and progression of human mammary epithelial cells, we examined the ability of [11C]choline (CHO) positron emission tomography imaging to detect clinically aggressive phenotype in patients with estrogen receptor (ER)–positive breast cancer in vivo. Experimental Design: CHO positron emission tomography was done in 32 individuals with primary or metastatic ER–positive breast cancer. Semiquantitative (standardized uptake value) and fully quantitative (net irreversible transfer rate constant of CHO, Ki) estimates of CHO uptake in the tumors were calculated and compared with tumor grade, size, involved nodes, and also ER, progesterone receptor, Ki-67, and human epidermal growth factor receptor-2 scores. Results: Breast tumors were well visualized in 30 of 32 patients with good tumor background ratios. A wide range of uptake values were observed in primary and metastatic tumors. CHO uptake variables correlated well with tumor grade. For most imaging variables, a poor association was found with tumor size, ER, progesterone receptor, human epidermal growth factor receptor-2, Ki-67, and nodal status. Conclusions: CHO showed good uptake in most breast cancers and merits further investigation as a breast cancer imaging agent. (Clin Cancer Res 2009;15(17):5503–10)
Effects of Tityus Serrulatus Scorpion Toxin gamma on Voltage-Gated Na sup + Channels
Authors: P. Marcotte, L.-Q. Chen, R.G. Kallen, M. Chahine
Journal: Circulation Research (1997)

The effects of Brazilian scorpion Tityus serrulatus toxin gamma (TiTx gamma) were studied on voltage-gated Na sup + channels from human heart (hH1) and rat skeletal muscle (rSkM1). The Na sup + channels were expressed in Xenopus laevis oocytes, and Na sup + currents were recorded using two-microelectrode voltageclamp techniques. In control experiments, the threshold of activation of hH1 is more negative than that of rSkM1 by [nearly =]20 mV. The toxin induces a shift of the voltage dependence of activation toward more negative potential values and reduces the amplitude of the current when administered to rSkM1. In contrast, TiTx gamma has little discernible effect on the current-voltage curve for hH1 at 100 nmol/L. Chimeric channels formed from these two isoforms were constructed to localize the binding site of TiTx gamma on rSkM1. TiTx gamma shifts the activation of a chimera (SSHH) in which domains 1 (D1) and 2 (D2) derive from rSkM1 and domains 3 (D3) and 4 (D4) derive from hH1. This finding suggests that the toxin acts on the activation of rSkM1 by binding either to D1 and/or D2. TiTx gamma shifted the activation of another chimera with D2-D3-D4 from rSkM1 (HSSS) toward more hyperpolarizing potentials and had no effect on the activation of other chimeras with only D1-D3-D4 from rSkM1 (SHSS) or only D3 from rSkM1 (HHSH). Finally, a chimera in which D2 is from rSkM1 and all others domains are from hH1 (HSHH) provides further compelling support for our hypothesis. TiTx gamma shifts the activation of this chimera toward more negative potential values. Thus, TiTx gamma action on chimeras segregates with the source of D2: when D2 is from rSkM1, the toxin affects activation. We infer that D2 plays an important role in the activation process of voltage-gated Na sup + channels.
Alcohol Consumption and Plasma Concentration of C-Reactive Protein
Authors: Michelle A. Albert, Robert J. Glynn, Paul M Ridker
Journal: Circulation (2003)

Background— Moderate alcohol intake has been associated with lower cardiovascular mortality. However, data evaluating the relationship between C-reactive protein (CRP), a predictor of cardiovascular risk, and alcohol consumption are sparse. Methods and Results— The relationship between alcohol consumption and CRP was evaluated in a cross-sectional survey and over time among 1732 men and 1101 women participating in the Pravastatin Inflammation/CRP Evaluation Study. CRP levels were lower in those with moderate alcohol intake versus light or occasional intake: in 5 categories of alcohol intake (no alcohol or &lt;1 drink monthly, 1 to 3 drinks monthly, 1 to 4 drinks weekly, 5 to 7 drinks weekly, and ≥2 drinks daily), median CRP levels were 2.60 mg/L (interquartile range (IQR), 1.20 to 5.30 mg/L), 2.20 mg/L (IQR, 1.00 to 4.40 mg/L), 1.70 mg/L (IQR, 0.80 to 3.80 mg/L), 1.60 mg/L (IQR, 0.80 to 3.30 mg/L), and 1.80 mg/L (IQR, 0.80 to 2.90 mg/L), respectively. This relationship was present among men, women not taking hormone replacement therapy, nonsmokers, and those individuals with and without a history of cardiovascular disease (all P &lt;0.001). In multivariate analysis, the relationship between alcohol consumption and CRP remained significant after controlling for multiple traditional cardiovascular risk factors. Alcohol consumption did not significantly affect the change in CRP or lipid levels associated with statin use. Conclusion— Moderate alcohol consumption was associated with lower CRP concentrations than no or occasional alcohol intake, an effect that was independent of alcohol-related effects on lipids. Alcohol may attenuate cardiovascular mortality in part through an anti-inflammatory mechanism.
Indwelling pleural catheters versus chest tube and talc pleurodesis in malignant pleural effusion
Authors: E Nuttall
Journal: Thorax (2012)

Indwelling pleural catheters versus chest tube and talc pleurodesis in malignant pleural effusionMalignant pleural effusion causes dyspnoea in more than 1 million people annually and current guidelines recommend chest tube insertion and talc slurry as first-line treatment.This unblinded randomised controlled trial aimed to determine whether indwelling pleural catheters (IPCs) are more effective at relieving dyspnoea in patients with malignant effusions than chest tube and talc pleurodesis.One hundred and six patients were recruited from 7 UK centres between April 2007 and February 2011 and were followed up for a year.The primary outcome was mean daily dyspnoea over the first 42 days as measured by the patients by a 100-mm line visual analogue scale measured by two independent researchers.The study showed that patient reported dyspnoea improved in both groups, but there was no significant difference between the IPC group and the talc group.No significant difference between the groups was shown for chest pain for the duration of the trial, survival time up to a year or quality of life at any time point.Over 12 months the IPC group spent a median of 1 day in hospital compared with 4.5 days for the talc group.The IPC group was associated with an increase in adverse events (21 of 52) compared with talc (7 of 54).Cost analysis was not included but is currently in progress.The authors concluded that there was no significant difference in patient reported dyspnoea between IPCs and talc pleurodesis.They suggested indwelling catheters did reduce hospital stay but were associated with increased adverse events.
Effect of Climate Change on Allergenic Airborne Pollen in Japan
Authors: Reiko Kishikawa, Akemi Saito, Norio Sahashi, Chie Oshikawa, Nobuo Soh, Toshitaka Yokoyama, Tadao Enomoto, Toru Imai, Koji Murayama, Yuma Fukutomi, Kazuo Akiyama, Terufumi Shimoda, Tomoaki Iwanaga
Journal: Journal of Allergy and Clinical Immunology (2015)
Endobronchial ultrasound-guided lymph node biopsy with transbronchial needle forceps: a pilot study
Authors: F. J. F. Herth, H. Schuler, D. Gompelmann, N. Kahn, S. Gasparini, A. Ernst, M. Schuhmann, R. Eberhardt
Journal: European Respiratory Journal (2011)

One limitation of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is the size of the available needles, frequently yielding only cells for cytological examination. The aim of this pilot study was to evaluate the efficacy and safety of newly developed needle forceps to obtain tissue for the histological diagnosis of enlarged mediastinal lymph nodes. Patients with enlarged, positron emission tomography (PET)-positive lymph nodes were included. The transbronchial needle forceps (TBNF), a sampling instrument combining the characteristics of a needle (bevelled tip for penetrating through the bronchial wall) with forceps (two serrated jaws for grasping tissue) was used through the working channel of the EBUS-TBNA scope. Efficacy and safety was assessed. 50 patients (36 males and 14 females; mean age 51 yrs) with enlarged or PET-positive lymph nodes were included in this pilot study. In 48 (96%) patients penetration of the bronchial wall was possible and in 45 patients tissue for histological diagnosis was obtained. In three patients TBNF provided inadequate material. For patients in whom the material was adequate for a histological examination, a specific diagnosis was established in 43 (86%) out of 50 patients (nonsmall cell lung cancer: n=24; small cell lung cancer: n=7; sarcoidosis: n=4; Hodgkin9s lymphoma: n=4; tuberculosis: n=2; and non-Hodgkin’s lymphoma: n=2).No clinically significant procedure-related complications were encountered. This study demonstrated that EBUS-TBNF is a safe procedure and provides diagnostic histological specimens of mediastinal lymph nodes.
Randomised controlled crossover trial of humidified continuous positive airway pressure in mild obstructive sleep apnoea
Authors: N S Marshall
Journal: Thorax (2005)

<b>Background:</b> It is unclear whether continuous positive airway pressure (CPAP), the treatment of choice for severe obstructive sleep apnoea (OSA), is effective at improving outcomes in mild OSA. <b>Methods:</b> To help define the role of humidified CPAP in mild OSA, a randomised crossover study was undertaken of patients with an apnoea hypopnoea index (AHI) of 5–30/hour. Subjective sleepiness, objective wakefulness, mood, reaction time, and quality of life were measured at baseline, after 3 weeks treatment with humidified CPAP and 3 weeks sham CPAP (2 week washout). <b>Results:</b> Twenty nine of 31 enrolled patients (age 25–67 years, seven women, mean (SD) body mass index 31.5 (6) kg/m<sup>2</sup>) completed the protocol. Humidified CPAP improved polysomnographic indices of OSA and Epworth Sleepiness Scale (2.4 points (95% CI 0.6 to 4.2)). Objective wakefulness (modified maintenance of wakefulness test) showed a trend towards improvement (5.2 minutes (95% CI −0.6 to 11)). Mood (Hospital Anxiety and Depression Scale), quality of life (SF 36, Functional Outcomes of Sleep Questionnaire), and reaction times (Psychomotor Vigilance Task) were not improved more than sham CPAP. Compliance with humidified and sham CPAP both averaged 4.9 hours/night. Placebo effects were evident in many outcomes and there was no clear treatment preference. <b>Conclusions:</b> Humidified CPAP improves subjective sleepiness and possibly objective wakefulness but not reaction times, quality of life, or mood. These results do not support the routine use of CPAP in all patients with mild OSA, but offers some support for the trialling of CPAP in those with severe sleepiness.
Isolation of a Natural Inhibitor of Human Malignant Glial Cell Invasion: Inter α-Trypsin Inhibitor Heavy Chain 2
Authors: Tamra E. Werbowetski-Ogilvie, Nathalie Y.R. Agar, Roberta M. Waldkircher de Oliveira, Damien Faury, Jack P. Antel, Nada Jabado, Rolando F. Del Maestro
Journal: Cancer Research (2006)

Abstract Malignant central nervous system (CNS) tumors, such as glioblastoma multiforme, invade the brain and disrupt normal tissue architecture, making complete surgical removal virtually impossible. Here, we have developed and optimized a purification strategy to isolate and identify natural inhibitors of glioma cell invasion in a three-dimensional collagen type I matrix. Inter α-trypsin inhibitor heavy chain 2 (ITI H2) was identified from the most inhibitory fractions and its presence was confirmed both as a single protein and in a bikunin-bound form. Stable overexpression in U251 glioma cells validated ITI H2′s strong inhibition of human glioma cell invasion together with significant inhibition of cell proliferation and promotion of cell-cell adhesion. Analysis of primary human brain tumors showed significantly higher levels of ITI H2 in normal brain and low-grade tumors compared with high-grade gliomas, indicating an inverse correlation with malignancy. The phosphatidylinositol 3-kinase/Akt signaling cascade seemed to be one of the pathways involved in the effect of ITI H2 on U251 cells. These findings suggest that reduction of ITI H2 expression correlates with brain tumor progression and that targeting factors responsible for its loss or restoring the ITI supply exogenously may serve as potential therapeutic strategies for a variety of CNS tumors. (Cancer Res 2006; 66(3): 1464-72)
Suppression of Th2 and Tfh immune reactions by Nr4a receptors in mature T reg cells
Authors: Takashi Sekiya, Taisuke Kondo, Takashi Shichita, Rimpei Morita, Hiroshi Ichinose, Akihiko Yoshimura
Journal: The Journal of Experimental Medicine (2015)

Regulatory T (T reg) cells are central mediators of immune suppression. As such, T reg cells are characterized by a distinct pattern of gene expression, which includes up-regulation of immunosuppressive genes and silencing of inflammatory cytokine genes. Although an increasing number of transcription factors that regulate T reg cells have been identified, the mechanisms by which the T reg cell–specific transcriptional program is maintained and executed remain largely unknown. The Nr4a family of nuclear orphan receptors, which we recently identified as essential for the development of T reg cells, is highly expressed in mature T reg cells as well, suggesting that Nr4a factors play important roles even beyond T reg cell development. Here, we showed that deletion of Nr4a genes specifically in T reg cells caused fatal systemic immunopathology. Nr4a-deficient T reg cells exhibited global alteration of the expression of genes which specify the T reg cell lineage, including reduction of Foxp3 and Ikzf4. Furthermore, Nr4a deficiency abrogated T reg cell suppressive activities and accelerated conversion to cells with Th2 and follicular helper T (Tfh) effector-like characteristics, with heightened expression of Th2 and Tfh cytokine genes. These findings demonstrate that Nr4a factors play crucial roles in mature T reg cells by directly controlling a genetic program indispensable for T reg cell maintenance and function.
A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype
Authors: Anne-Marie Malfait, Albert B Seymour, Feng Gao, Micky D Tortorella, Marie-Pierre Hellio Le Graverand-Gastineau, Linda S Wood, Michael Doherty, Sally Doherty, Weiya Zhang, Nigel K Arden, Frances L Vaughn, Paul E Leaverton, Tim D Spector, Deborah J Hart, Rose A Maciewicz, Kenneth R Muir, Rosalina Das, Robert E Sorge, Susanna G Sotocinal, Ara Schorscher-Petcu, Ana M Valdes, Jeffrey S Mogil
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Purpose:</h3> To identify specific actions and characteristics of health care providers (HCPs) in the United States and Canada that influenced patients with type 2 diabetes who were initially reluctant to begin insulin. <h3>Methods:</h3> Patients from the United States (n = 120) and Canada (n = 74) were recruited via registry, announcements, and physician referrals to complete a 30-minute online survey based on interviews with patients and providers regarding specific HCP actions that contributed to the decision to begin insulin. <h3>Results:</h3> The most helpful HCP actions were patient-centered approaches to improve patients' understanding of the injection process (ie, "My HCP walked me through the whole process of exactly how to take insulin" [helped moderately or a lot, United States: 79%; Canada: 83%]) and alleviate concerns ("My HCP encouraged me to contact his/her office immediately if I ran into any problems or had questions after starting insulin" [United States: 76%; Canada: 82%]). Actions that were the least helpful included referrals to other sources (ie, "HCP referred patient to a class to help learn more about insulin" [United States: 40%; Canada: 58%]). <h3>Conclusions:</h3> The study provides valuable insight that HCPs can use to help patients overcome psychological insulin resistance, which is a critical step in the design of effective intervention protocols.
Association of autoantibodies to filaggrin with an active disease in early rheumatoid arthritis
Authors: L Paimela
Journal: Annals of the Rheumatic Diseases (2001)

To evaluate the clinical significance of antifilaggrin antibodies (AFA) measured by an enzyme linked immunosorbent assay (ELISA) in serial specimens from patients with recent onset rheumatoid arthritis (RA).Filaggrin was purified from human skin and used as an antigen in ELISA. The AFA test was applied to five serial specimens from 78 patients with recent onset RA followed up for three years. Rheumatoid factor (RF) had been measured earlier from the same samples by quantitative immunoturbidimetry.The mean AFA level was highest at entry (54% positive), followed by a statistically significant decline at six months and a slight increase at three years. AFA were persistently positive in 23 patients and persistently negative in 28 patients. Eleven of the latter patients were persistently negative for RF. At study entry AFA levels correlated to some degree with RF levels. In general, raised AFA levels at entry were associated with an active and treatment resistant disease, but they did not predict radiological progression.The test for AFA has potential for an additional immunological test for RA.