tbuckley/cabot-search huggingface dataset:
Rapid and Ultrarapid Opioid Detoxification Techniques
Authors: Patrick G. O'Connor
Journal: JAMA (1998)

Objective.—To review the scientific literature on the effectiveness of rapid opioid detoxification (RD) (opioid withdrawal precipitated by naloxone hydrochloride or naltrexone) and ultrarapid opioid detoxification (URD) (opioid withdrawal precipitated by naloxone or naltrexone under anesthesia or heavy sedation) techniques.Data Sources.—The MEDLINE database was searched from 1966 through 1997 using the indexing terms naloxone, naltrexone, substance dependence, and substance withdrawal syndrome. Additional data sources included bibliographies of papers identified on MEDLINE and bibliographies in textbooks on substance abuse.Study Selection.—Inclusion criteria were studies of RD or URD, pharmacologic protocols specified, and clinical outcomes specified and reported. Exclusion criteria were unpublished data, data not in peer-reviewed journals, abstract-only publications, and review articles.Data Extraction.—The methodologic characteristics of studies were extracted by the authors and summarized according to key components of research design concerning subject characteristics, therapy allocation, and outcomes assessed.Data Synthesis.—A qualitative analysis was performed on the 12 studies of RD and the 9 studies of URD identified in our search. The RD studies enrolled 641 subjects (range for individual studies, 1-162): 7 were inpatient studies, and the protocols varied considerably, as did the outcomes assessed. Three RD studies included a control group, 2 used a randomized design, and 3 reported outcomes beyond 12 days. The URD studies enrolled 424 subjects (range for individual studies, 6-300): all were inpatient studies, the detoxification and anesthesia protocols varied, 3 included a control group, 2 used a randomized design, and 2 reported outcomes for URD beyond 7 days.Conclusions.—The existing literature on RD and URD is limited in terms of the number of subjects evaluated, the variation in protocols studied, lack of randomized design and use of control groups, and the short-term nature of the outcomes reported. Further research is needed using more rigorous research methods, longer-term outcomes, and comparisons with other methods of treatment for opioid dependence.
Impaired Lymphocyte Transformation in Hodgkin's Disease. EVIDENCE FOR DEPLETION OF CIRCULATING T-LYMPHOCYTES
Authors: Kenneth M. Matchett, Andrew T. Huang, William B. Kremer
Journal: Journal of Clinical Investigation (1973)

The kinetics of lymphocyte transformation induced by phytohemagglutinin (PHA) and pokeweed mitogen (PWM) were studied daily, with blood lymphocytes from normal individuals and from untreated patients in all stages of Hodgkin's disease (HD). In addition, spleen lymphocytes and lymph node lymphocytes were studied with similar techniques.Peripheral blood lymphocyte transformation stimulated by PHA was found to be depressed in all patients with HD (including those with localized disease and no symptoms) when small numbers of lymphocytes were cultured and studied during a 7-day period. Most patients with HD had an increased number of cells circulating in their blood which were actively synthesizing DNA. HD lymphocytes which demonstrated the highest initial rate of spontaneous DNA synthesis usually did not respond to PHA stimulation. Blood lymphocytes from normal individuals responded equally well to PHA and PWM in our system. HD blood lymphocytes consistently responded better to PWM than to PHA, with the response to PWM frequently within the normal range. Unless the spleen was extensively infiltrated with HD, spleen lymphocytes from patients with HD responded to PHA, even though the blood lymphocyte response was severely reduced. Lymph node lymphocyte response to PHA from patients with HD was variable, but correlated roughly with the blood lymphocyte response. It is hypothesized from the data presented that in HD, circulating thymus-dependent (T-)lymphocytes are stimulated by the presence of active disease. This stimulation of T-lymphocytes leads to a circulating T-cell depletion and to an increase in the number of cells circulating that are active in DNA synthesis. The degree of impairment of cell-mediated immunity would then depend upon the degree of T-lymphocyte depletion.
Hypoxic Stress Induces Dimethylated Histone H3 Lysine 9 through Histone Methyltransferase G9a in Mammalian Cells
Authors: Haobin Chen, Yan Yan, Todd L. Davidson, Yoichi Shinkai, Max Costa
Journal: Cancer Research (2006)

Abstract Dimethylated histone H3 lysine 9 (H3K9me2) is a critical epigenetic mark for gene repression and silencing and plays an essential role in embryogenesis and carcinogenesis. Here, we investigated the effects of hypoxic stress on H3K9me2 at both global and gene-specific level. We found that hypoxia increased global H3K9me2 in several mammalian cell lines. This hypoxia-induced H3K9me2 was temporally correlated with an increase in histone methyltransferase G9a protein and enzyme activity. The increase in H3K9me2 was significantly mitigated in G9a−/− mouse embryonic stem cells following hypoxia challenge, indicating that G9a was involved in the hypoxia-induced H3K9me2. In addition to the activation of G9a, our results also indicated that hypoxia increased H3K9me2 by inhibiting H3K9 demethylation processes. Hypoxic mimetics, such as deferoxamine and dimethyloxalylglycine, were also found to increase H3K9me2 as well as G9a protein and activity. Finally, hypoxia increased H3K9me2 in the promoter regions of the Mlh1 and Dhfr genes, and these increases temporally correlated with the repression of these genes. Collectively, these results indicate that G9a plays an important role in the hypoxia-induced H3K9me2, which would inhibit the expression of several genes that would likely lead to solid tumor progression. (Cancer Res 2006; 66(18): 9009-16)
1099 MESENCHYMAL STEM CELLS MODIFIED TO EXPRESS INTERFERON-b INHIBIT THE GROWTH OF HEPATOCELLULAR CANCER THROUGH INHIBITING AKT/FOXO3a PATHWAY
Authors: C. Xie, J.-Q. Xie, Q.-S. Zhang, L. Peng, G.-L. Zhang, D.-Y. Xie, Z.-L. Gao
Journal: Journal of Hepatology (2013)
The type I IFN signature as a biomarker of preclinical rheumatoid arthritis
Authors: Joyce Lübbers, Mikael Brink, Lotte A van de Stadt, Saskia Vosslamber, John G Wesseling, Dirkjan van Schaardenburg, Solbritt Rantapää-Dahlqvist, Cornelis L Verweij
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To validate the presence and demonstrate the clinical value of the type I interferon (IFN)-signature during arthritis development. <h3>Method</h3> In 115 seropositive arthralgia patients who were followed for the development of arthritis (Amsterdam Reade cohort), and 25 presymptomatic individuals who developed rheumatoid arthritis (RA) later, and 45 population-based controls (Northern Sweden cohort), the expression levels of 7 type I IFN response genes were determined with multiplex qPCR and an IFN-score was calculated. The diagnostic performance of the IFN-score was evaluated using Cox regression and Receiver Operating Characteristics (ROC)-curve analysis. <h3>Results</h3> In 44 of the 115 at-risk individuals (38%) from the Amsterdam Reade cohort, arthritis developed after a median period of 8 months (IQR 5–13). Stratification of these individuals based on the IFN-score revealed that 15 out of 25 IFN<sup>high</sup> individuals converted to arthritis, compared with 29 out of 90 IFN<sup>low</sup> individuals (p=0.011). In the Northern Sweden cohort, the level of the IFN-score was also significantly increased in presymptomatic individuals who developed RA compared with population-based controls (p=0.002). Cox regression analysis of the Amsterdam Reade cohort showed that the hazard ratio (HR) for development of arthritis was 2.38 (p=0.008) for IFN<sup>high</sup> at-risk individuals after correction for anticitrullinated protein antibodies (ACPA) and rheumatoid factor (RF). The ROC-curve area under the curve (AUC) for the IFN-score combined with ACPA and RF in the prediction of arthritis was 78.5% (p=0.0001, 95% CI 0.70 to 0.87). <h3>Conclusions</h3> The results demonstrated clinical utility for the IFN-signature as a biomarker in the prediction of arthritis development.
Comparative Effectiveness of Oxaliplatin vs Non–Oxaliplatin-containing Adjuvant Chemotherapy for Stage III Colon Cancer
Authors: Hanna K. Sanoff, William R. Carpenter, Christopher F. Martin, Daniel J. Sargent, Jeffrey A. Meyerhardt, Til Stürmer, Jason P. Fine, Jane Weeks, Joyce Niland, Katherine L. Kahn, Maria J. Schymura, Deborah Schrag
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundThe addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.
The first 20 minutes after a single dose of inhaled salmeterol in asthmatic children
Authors: A. Barbato, A. Cracco, F. Tormena, A. Novello
Journal: Allergy (1995)

Very little is known as yet about the effect of salmeterol in pediatric asthma, so a trial was performed on children with mild asthma to compare salmeterol with salbutamol in terms of how quickly they took effect. The double‐blind study involved 11 children (mean age 13.4 years) randomly assigned to inhale salmeterol 50 μg, salbutamol 200 μg, or a placebo three times on alternate days. Peak expiratory flow (PEF), heart rate, and blood pressure were measured before and 5, 10, 15, and 20 min after administering the medication. With salbutamol, PEF was higher at 5 and 10 min, subsequently dropping off at 15 and 20 min; with salmeterol, PEF was better at 10 and 20 min. Forced expiratory volume at 1 s (FEV 1 ) measurements taken at the baseline and after 10 and 20 min revealed an important and consistent rise in values after salmeterol, whereas salbutamol was more effective after 10 min than after 20 min. No significant changes were recorded in heart rate or blood pressure after salbutamol; after salmeterol, there was a significant increase in heart rate after 5 min, but not at subsequent measurements. In conclusion, salmeterol begins to take effect already within 10 min of a single administration in asthmatic children, although the onset of its effect is slower than with salbutamol.
Induction of Retinol Dehydrogenase 9 Expression in Podocytes Attenuates Kidney Injury
Authors: Xuezhu Li, Yan Dai, Peter Y. Chuang, John Cijiang He
Journal: Journal of the American Society of Nephrology (2014)

The intracellular concentration of retinoic acid is determined by two sequential oxidation reactions that convert retinol to retinoic acid. We recently demonstrated that retinoic acid synthesis is significantly impaired in glomeruli of HIV-1 transgenic mice (Tg26), a murine model of HIV-associated nephropathy. This impaired retinoic acid synthesis correlates with reduced renal expression of retinol dehydrogenase 9, which catalyzes the rate-limiting step of retinoic acid synthesis by converting retinol to retinal. Because retinoic acid has renal protective effects and can induce podocyte differentiation, we hypothesized that restoration of retinoic acid synthesis could slow the progression of renal disease. Herein, we demonstrate that overexpression of retinol dehydrogenase 9 in cultured podocytes induces the expression of podocyte differentiation markers. Furthermore, we confirm that podocyte-specific overexpression of retinol dehydrogenase 9 in mice with established kidney disease due to either HIV-associated nephropathy or adriamycin-induced nephropathy decreases proteinuria, attenuates kidney injury, and restores podocyte differentiation markers. Our data suggest that restoration of retinoic acid synthesis could be a new approach to treat kidney disease.
Serum amyloid A as a potential biomarker of sarcoidosis
Authors: Elena Bargagli, Carmela Olivieri, Claudia Landi, Barbara Magi, David Bennett, Nicola Bianchi, Anna Perrone, Antonella Fossi, Paola Rottoli
Journal: European Respiratory Journal (2011)

At the beginning of our studies on proteomics we compared serum protein profiles in interstitial lung diseases and we found increased expression of certain acute phase proteins, such as serum amyloid A (SAA), in sarcoidosis serum samples.  An increased expression of SAA1 was detected by a proteomic approach (two-dimensional electrophoresis) in serum of sarcoidosis patients, therefore we decided to validate this finding evaluating its concentrations by a quantitative assay (ELISA) and to further investigate SAA patterns in patients with sarcoidosis.  Our population consisted of 48 patients affected by sarcoidosis and 17 healthy controls. Patients were divided according to phenotype activity score SCAC. Proteomic analysis of SAA in serum revealed that the protein resolved in 2 different spots with isoelectric point/molecular weight of 5.69/11000 KDa and 6.15/11000 Kda. SAA1 spots were never observed in samples of healthy subjects but only in sarcoidosis patients. ELISA assay reported significantly higher concentrations of SAA in patients than controls (p=0.002). Protein concentrations inversely correlated with FEV1 percentages in sarcoidosis patients and were significantly higher in SCAC group 6 than in SCAC group 4 (p  Interestingly the molecular weight of the two isoforms of SAA identified in our study corresponded to two unidentified serum proteins, proposed as sarcoidosis biomarker, in a previous proteomic study performed by Bons et al.  In conclusion SAA could be a useful biomarker of sarcoidosis since its levels are significantly higher in patients than controls, especially in those with lung function impairment and requiring prolonged steroid treatment.
Elevated Blood Lead Concentrations in Essential Tremor: A Case–Control Study in Mersin, Turkey
Authors: Okan Dogu, Elan D. Louis, Lulufer Tamer, Ozgur Unal, Arda Yilmaz, Hakan Kaleagasi
Journal: Environmental Health Perspectives (2007)

BackgroundEssential tremor (ET) is one of the most common neurologic disorders. Aside from underlying susceptibility genes, recent studies have also begun to focus on environmental toxic factors. Yet there remains a paucity of information on such factors, making studies of environmental factors important. A recent study in New York City found blood lead concentrations to be elevated in ET cases compared with matched controls. Chronic exposure to lead produces cerebellar damage, and this could predispose individuals to develop ET.ObjectiveThe aim of this study was to determine whether the elevation in blood lead concentrations observed in a single study in New York was similarly present in ET cases sampled from a completely different geographic region.MethodsBlood lead concentrations were measured in 105 ET cases and 105 controls at Mersin University, Mersin, Turkey.ResultsThe median blood lead concentration was 2.7 μg/dL in ET cases compared with 1.5 μg/dL in controls (p < 0.001). In an unadjusted logistic regression model, blood lead concentration was associated with diagnosis: odds ratio (OR) = 4.01; 95% confidence interval (CI), 2.53–6.37; p < 0.001 (i.e., each 1-μg/dL increase in blood lead concentration was associated with a 4-fold increased odds of ET). This association was more robust when cases were compared with a subsample of controls who did not share the same home environment (OR = 8.13; 95% CI, 3.05–21.65; p < 0.001). In adjusted models, results were similar.ConclusionsThese data replicate those of a previous study in New York and demonstrate an association between the environmental toxicant lead and a common neurologic disorder.
P172 Time Trends in Incidence and Prevalence of Bronchiectasis in the UK: Abstract P169 Table 1
Authors: JK Quint, E Millett, JR Hurst, L Smeeth, J Brown
Journal: Thorax (2012)

<h3>Background</h3> The incidence of bronchiectasis in the UK is unknown. No large study has been performed in the UK since the 1950s<sup>1</sup>and there are few relevant data from non-UK sources. The prevalence is likely to be relatively high as bronchiectasis is a chronic condition, and case ascertainment is increasing with the wider availability of CT scanning. Establishing the healthcare burden is essential for informing allocation of healthcare resources and improving patient experience. <h3>Methods</h3> All individuals in the general practise research database (CPRD-GOLD) between 1st January 2004 and 31stDecember 2011 were included. Currently this includes information from 640General Practises in the UK. From this cohort, patients with a diagnosis of bronchiectasis were identified using specific READ codes. We calculated the absolute incidence rates and prevalence of bronchiectasis by calendar year, age and gender. <h3>Results</h3> Over the 8 year time period 27,258 individuals (0.7%) had a diagnosis of bronchiectasis. The overall incidence increased overtime; 2004 incidence 18/100,000 person years at risk and in 2011 the incidence was 32/100,000 person years at risk. Prevalence also increased year on year, was higher in older age groups (&gt; 60 years of age) and was higher in women than in men. The prevalence in 2011 in men and women by age is provided in Table 1. <h3>Conclusions</h3> Bronchiectasis is a relatively common condition in 2011 in the UK, particularly in individuals over the age of 60. Part of the increase in prevalence over time may be due to increasing numbers of CT scans being performed. How the prevalence relates to individual disease burden and health careutilisation is yet to be established. <h3>References</h3> Guideline for non-CF Bronchiectasis, British Thoracic Society (July 2010).
Acquisition of murine major histocompatibility complex gene products by schistosomula of Schistosoma mansoni.
Authors: A Sher, B F Hall, M A Vadas
Journal: The Journal of Experimental Medicine (1978)

Schistosoma mansoni schistosomula recovered from the lungs of inbred mice were shown to possess serologically detectable alloantigens on their tegumental surfaces. Using appropriate antisera and infected congenic and recombinant mice as worm donors, gene products of the K and I subregions of the major histocompatibility complex were demonstrated among these alloantigens acquired by the parasites. In contrast, other cell surface alloantigens, such as Thy 1, Ly 1, and H-Y and the serum proteins albumin, C3 and Ig, could not be detected on the surface of lung schistosomula by means of comparable techniques. In another series of experiments, schistosomula recovered from the lungs of mice and reinjected into allogeneic recipients were shown to exchange their alloantigens during an 87-h period of examination. Similarly, lung schistosomula cocultured with allogeneic lymphocytes were shown to acquire major histocompatibility complex (MHC) coded antigens from the cells. It is possible that as acquired host molecules, MHC gene products may disguise the surface of schistosome parasites thereby rendering them insusceptible to immune attack.
Activation of Hypoxia-Inducible Factor-1α Is Necessary for Lysophosphatidic Acid–Induced Vascular Endothelial Growth Factor Expression
Authors: Jangsoon Lee, Soon Young Park, Eun Kyung Lee, Chang Gyo Park, Hyun Cheol Chung, Sun Young Rha, Yong Kee Kim, Gyu-Un Bae, Bum Kyeong Kim, Jeung-Whan Han, Hoi Young Lee
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Lysophosphatidic acid (LPA) plays an important role in mediating cell proliferation, survival, and tumor invasion and angiogenesis. This bioactive phospholipid at the concentration in ascitic fluid stimulates the growth of malignant ovarian tumors by increasing the expression of vascular endothelial growth factor (VEGF). In the present study, we investigated whether LPA activates hypoxia inducible factor-1 (HIF-1), a key transcriptional complex in tumor progression and metastasis, thereby increasing the expression of VEGF. Experimental Design: Immunoblotting, reverse transcription-PCR, ELISA, immunofluorescence, and chromatin immunoprecipitation assay were used to examine the expression of VEGF and HIF-1α in various cancer cells. Specific HIF-1α small interfering RNA was transfected to various cancer cells to determine the role of HIF-1α in LPA-induced VEGF expression. Results: LPA induced expressions of VEGF and HIF-1α in OVCAR-3, CAOV-3, PC-3, and SK-Hep1 cells but not in SKOV-3 and Hep-3B cells. In OVCAR-3 and PC-3 cells, the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin/p70S6K and p42/p44 mitogen-activated protein kinase pathways were required for LPA-induced HIF-1α and VEGF expressions, whereas only the phosphoinositide 3-kinase/mammalian target of rapamycin/p70S6K pathway was important in SK-Hep1 cells. Immunofluorescence microscopy assay showed translocation of HIF-1α to nucleus by LPA, and chromatin immunoprecipitation assay revealed the binding of HIF-1α to the promoter of VEGF by LPA. Importantly, we found that small interfering RNA–induced reduction of HIF-1α expression significantly attenuated VEGF expression by LPA. Conclusions: Our results show for the first time that LPA induces VEGF via HIF-1α activation and reveal a critical role of HIF-1α in LPA-induced cancer cell proliferation and angiogenesis.
Influence of ambient air on NMR-based metabolomics of exhaled breath condensates
Authors: Jose L. Izquierdo-García, Germán Peces-Barba, Jesús Ruiz-Cabello
Journal: European Respiratory Journal (2012)

To the Editors:

Nuclear magnetic resonance (NMR)-based metabolomic analysis of exhaled breath condensate (EBC) is a noninvasive approach that has been used to study diseases of the respiratory system [1, 2]. In a previous study, we questioned the accuracy of NMR-based EBC analysis, demonstrating that the cleaning protocols for reusable condenser parts produce a confounding metabolite fingerprint largely unrelated to the endogenous metabolites from the airways and alveolar fractions of exhaled breath [3]. Here we present new data that provide a qualitative assessment of exogenous contaminants in NMR spectroscopy analysis of EBC, some proceeding from room air. Given the presence of these contaminants in the NMR spectrum, classification of these components as biomarkers of lung function should be regarded with extreme caution. Previous studies have reported the presence of room air components in mass spectrometry analysis of volatiles in exhaled human breath [4, 5] and non-volatiles in exhaled human breath condensate [6]. However, although a previous NMR-based metabolomic study of EBC reported the presence of external impurities such as disinfectants or salivary signals [1], the influence of contaminating metabolites in room air was not considered.

In order to analyse the influence of exogenous signals on EBC analysis, room air condensate and EBC from a healthy volunteer were collected with an EcoScreen condenser (Jaeger, Wurzburg, Germany). The samples of room air condensate were acquired with a device that continuously pumps room air into the condenser at a flow rate (15 L·min−1) and tidal volume (500 mL) typical of normal human breathing. The typical time required for sample acquisition was 15 min. Another set of room air samples was collected by locating a trap for air-contained water-soluble organic compounds between the pump and the condenser to study the …