tbuckley/cabot-search huggingface dataset:
Users' Guides to the Medical Literature
Authors: Gordon H. Guyatt
Journal: JAMA (1994)

<h3>CLINICAL SCENARIO</h3> You are a general internist who is asked to see a 65-year-old man with controlled hypertension and a 6-month history of atrial fibrillation resistant to cardioversion. Although he has no evidence for valvular or coronary heart disease, the family physician who referred him to you wants your advice on whether the benefits of long-term anticoagulants (to reduce the risk of embolic stroke) outweigh their risks (of hemorrhage from anticoagulant therapy). The patient shares these concerns and doesn't want to receive a treatment that would do more harm than good. You know that there have been randomized trials of warfarin for nonvalvular atrial fibrillation and decide that you'd better review one of them.
Effects of obstructive sleep apnoea on systemic inflammation and adipose tissue expression of CD40, MKK4 and JNK
Authors: Pavol Joppa, Viera Habalova, Miroslav Brusik, Lucia Klimcakova, Zuzana Sopkova, Ruzena Tkacova
Journal: European Respiratory Journal (2014)

Background : Hypoxia-induced activation of nuclear factor kappa B (NFkappaB) modulates the transcription of multiple target genes. A transmembrane receptor of the tumor necrosis factor (TNF) gene superfamily CD40 orchestrates the process of inflammation through secondary messengers - mitogen activated protein kinase kinase 4 (MKK4) and c-Jun NH2-terminal kinases (JNK).   Objectives : We analyzed the effects of obstructive sleep apnoea (OSA) on serum TNFalpha and its soluble receptors (sTNF-RI, sTNF-RII), and on adipose tissue (AT) NFkappaB, CD40, MKK4 and JNK mRNA expressions.   Methods : 25 male subjects (17 with severe OSA, 8 controls) underwent overnight polysomnography. Samples of subcutaneous AT were analyzed using rtPCR.   Results : Circulatory sTNF-RI and sTNF-RII correlated directly with transcutaneous O 2  saturation l90% (R=0.458, p=0.003; R=0.335, p=0.035); sTNF-RII correlated also with apnoea-hypopnoea and oxygen desaturation indices (R=0.358, p=0.024; R=0.324, p=0.041). Compared to controls, patients with OSA had significantly lower AT expressions of CD40, MKK4 and JNK [1.03±0.3 vs 1.34±0.3 ΔΔCt, p=0.026; 1.06±0.28 vs 1.38±0.17 ΔΔCt, p=0.005; 1.09±0.45 vs 1.48±0.37 ΔΔCt, p=0.037, respectively]. No differences were observed in NFkappaBI, NFkappaBII or TNFalpha AT expressions between the two groups.   Conclusions : In OSA, systemic inflammation reflected by increases in serum sTNF-RII is not related to AT CD40, MKK4 and JNK gene expressions. Further studies are needed to explore the role of intermittent hypoxia in systemic inflammation in patients with OSA.    Funding:  APVV-0134-11, VEGA 1/0111/12, Slovakia.
Increasing the age for the legal purchase of tobacco in England: impacts on socio-economic disparities in youth smoking
Authors: C. Millett, J. T. Lee, D. C. Gibbons, S. A. Glantz
Journal: Thorax (2011)

<h3>Background</h3> The minimum age for the legal purchase of tobacco increased from 16 to 18 years in England, Scotland and Wales on 1 October 2007. The authors examined the impact of this legislation on disparities in smoking behaviour and access to cigarettes among youth in England. <h3>Methods</h3> A multivariate logistic regression analysis was carried out adjusting for secular trends in regular smoking using data from the Smoking, Drinking and Drug Use Survey, a national survey of 11–15 year olds. The primary outcome measure was regular smoking and the predictor variables were the law increasing the minimum age for purchase and eligibility for free school meals (FSM). <h3>Results</h3> Increasing the minimum age for purchase was associated with a significant reduction in regular smoking among youth (adjusted OR 0.67; 95% CI 0.55 to 0.81, p=0.0005). This effect was not significantly different in pupils eligible for FSM compared with those that were not (adjusted OR 1.29; 95% CI 0.95 to 1.76, p=0.10 for interaction term). The percentage of pupils who stated that they found it difficult to buy cigarettes from a shop did not increase in those eligible for FSM (25.2% to 33.3%; p=0.21) but did increase significantly in others (21.2% to 36.9%; p&lt;0.01) between 2006 and 2008. No differences in ease of purchase were found between pupils eligible for FSM and those not before or after the legislation (2006: p=0.34, 2008: p=0.55). <h3>Conclusions</h3> Increasing the age for the legal purchase of tobacco was associated with reduced regular smoking among youth in England and appeared to have a similar impact in different socio-economic groups.
Enhancement of ventricular gap-junction coupling by rotigaptide
Authors: Xianming Lin, Christian Zemlin, James K. Hennan, Jørgen S. Petersen, Richard D. Veenstra
Journal: Cardiovascular Research (2008)

Rotigaptide is proposed to exert its anti-arrhythmic effects by improving myocardial gap-junction communication. To directly investigate the mechanisms of rotigaptide action, we treated cultured neonatal murine ventricular cardiomyocytes with clinical pharmacological doses of rotigaptide and directly determined its effects on gap-junctional currents.
Bronchoalveolar lavage phospholipid abnormalities in HIV-infected patients
Authors: R Escamilla, MC Prevost, C Cariven, C Hermant, M Krempf, H Chap
Journal: European Respiratory Journal (1993)

Our aim was to evaluate the quality of pulmonary surfactant, a nonspecific defence system, during the course of human immunodeficiency virus) infection. Protein and phospholipid composition were determined in 127 bronchoalveolar lavage (BAL) fluids from 89 HIV seropositive patients (54 acquired immune deficiency syndrome (AIDS), 35 non-AIDS) and 11 healthy controls. In all of the HIV BAL samples, biochemical abnormalities were found. In subjects with pulmonary infection or Kaposi's sarcoma, the phospholipid/protein ratio was decreased, mainly because of elevated protein levels (15.8 and 20, respectively, vs 7.2 mg.100 ml-1 for controls, p < 0.05). In subjects without obvious pulmonary involvement, phospholipid was decreased (1.3 +/- 0.2 vs 2.9 +/- 0.3 mg.100 ml-1 for controls, p < 0.001), whereas the protein was not altered. Phospholipid composition was also altered: the phosphatidylcholine percentage was decreased, whilst the other main phospholipids were increased. We conclude that the alveolar lining is altered, whatever the stage of HIV disease. In most patients, it results from an increase of vascular permeability, with an influx of serum proteins. However, changes in phospholipid composition suggest that, in some cases, surfactant is also altered.
Workshop Report: Prevention and Early Treatment of NIDDM
Authors: Robert Wilson, Edward Horton
Journal: Diabetes Care (1993)

RESEARCH OPPORTUNITIES— Critical scientific and practical questions are whether it is possible to prevent NIDDM and whether early treatment of diabetes is effective. There are three potential strategies that may retard the development of prevention of NIDDM and which are also of importance in the early treatment of NIDDM—control of obesity, preservation of insulin action, and preservation of insulin secretion. The panel stressed the impact of exercise both on the control of obesity and the preservation of insulin action. A structured exercise program such as that conducted in the Zuni community can be made available to an entire community. The importance of community involvement in establishing and sustaining such programs, and the importance of using sound principles of effective behavior modification were recognized.
CELL-TO-CELL INTERACTION IN THE IMMUNE RESPONSE
Authors: J. F. A. P. Miller, J. Sprent, A. Basten, N. L. Warner, J. C. S. Breitner, G. Rowland, J. Hamilton, H. Silver, W. J. Martin
Journal: The Journal of Experimental Medicine (1971)

Experiments were designed to test the possibility that thymus-derived (T) cells cooperate with nonthymus derived (B) cells in antibody responses by acting as passive carriers of antigen. Thoracic duct lymphocytes (TDL) from fowl gammaG-tolerant mice were incubated in vitro with fowl anti-mouse lymphocyte globulin (FALG), which was shown not to be immunosuppressive in mice. On transfer into adult thymectomized, irradiated, and marrow protected (TxBM) hosts together with a control antigen, horse RBC, a response to horse RBC but not to fowl gammaG was obtained. By contrast, TxBM recipients of nontolerant, FALG-coated TDL responded to both antigens and the antibody-forming cells were shown to be derived from the host, not from the injected TDL. These findings suggested that, under the conditions of the experiment, triggering of unprimed B cells in the spleens of TxBM hosts was not achieved with antigen-coated tolerant lymphocytes. Another model utilized the ability of B cells to bind antibody-antigen complexes. Spleen cells from TxBM mice, incubated in vitro with anti-fowl gammaG-fowl gammaG.NIP, were injected with or without normal TDL (a source of T cells) into irradiated hosts. Only mice given both cell types could produce an anti-NIP antibody response. In a further experiment, spleen cells from HGG.NIP-primed mice were injected together with NIP-coated B cells (prepared as above) into irradiated hosts. A substantial anti-NIP antibody response occurred. If, however, the T cells in the spleens of HGG.NIP-primed mice were eliminated by treatment with anti-theta serum and complement, the NIP response was abolished. It was concluded that antigen-coated B cells could not substitute for T cells either in the primary or secondary response. Treatment of T cells from unprimed or primed mice with mitomycin C impaired their capacity to collaborate with B cells on transfer into irradiated hosts. Taken together these findings suggest that before collaboration can take place T cells must be activated by antigen to differentiate and in so doing may produce some factor essential for triggering of B cells.
Protective Effect of α-Lipoic Acid in Lipopolysaccharide-Induced Endothelial Fractalkine Expression
Authors: Mi Jeong Sung, Won Kim, So Young Ahn, Chung-Hyun Cho, Gou Young Koh, Sang-Ok Moon, Duk Hoon Kim, Sik Lee, Kyung Pyo Kang, Kyu Yun Jang, Sung Kwang Park
Journal: Circulation Research (2005)

Fractalkine is a unique chemokine that functions as a chemoattractant as well as an adhesion molecule on endothelial cells activated by proinflammatory cytokines. Alpha-lipoic acid (LA), a naturally occurring dithiol compound, is an essential cofactor for mitochondrial bioenergetic enzymes. LA improves glycemic control, reduces diabetic polyneuropathies, and mitigates toxicity associated with heavy metal poisoning. The effects of LA on processes associated with sepsis, however, are unknown. We evaluated the antiinflammatory effect of LA on fractalkine expression in a lipopolysaccharide-induced endotoxemia model. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) significantly induced fractalkine mRNA and protein expression in endothelial cells. LA strongly suppressed TNF-alpha- or IL-1beta-induced fractalkine expression in endothelial cells by suppressing the activities of nuclear factor-kappaB and specificity protein-1. LA also decreased TNF-alpha- or IL-1beta-stimulated monocyte adhesion to human umbilical vein endothelial cells. As shown by immunohistochemistry, fractalkine protein expression was markedly increased by treatment with lipopolysaccharide in arterial endothelial cells, endocardium, and endothelium of intestinal villi. LA suppressed lipopolysaccharide-induced fractalkine protein expression and infiltration of endothelin 1-positive cells into the heart and intestine in vivo. LA protected against lipopolysaccharide-induced myocardial dysfunction and improved survival in lipopolysaccharide-induced endotoxemia. These results suggest that LA could be an effective agent to reduce fractalkine-mediated inflammatory processes in endotoxemia.
Patent ductus arteriosus in infants and children: A review of 936 operations (1946-69)
Authors: Ph. G. Panagopoulos, C. J. Tatooles, E. Aberdeen, D. J. Waterston, R. E. B. Carter
Journal: Thorax (1971)

Nine hundred and thirty-six consecutive cases of closure of a patent ductus arteriosus in infants and children are reported. Among 789 without any other cardiac anomalies there were 11 deaths, seven of these with severe congenital anomalies other than cardiovascular. There was one incomplete closure. The deaths in this series were mostly associated with additional congenital cardiac anomalies. Forty-eight of the 59 who died had additional cardiac anomalies. Forty-seven of the deaths were in infants. For 691 patients over the age of 1 year the hospital mortality rate was less than 0·5%. Ligation of the ductus using two ligatures of thick plaited silk (1·2 mm diameter) was the technique used in 99% of these cases. There were four cases of recanalization or inadequate ligation but all four survived. This technique seems an acceptable one for the closure of a patent ductus arteriosus.
Somatic Mutations of <i>EGFR</i> Gene in Squamous Cell Carcinoma of the Head and Neck
Authors: Jong Woo Lee, Young Hwa Soung, Su Young Kim, Hyo Kyung Nam, Won Sang Park, Suk Woo Nam, Min Sik Kim, Dong Il Sun, Youn Soo Lee, Ja June Jang, Jung Young Lee, Nam Jin Yoo, Sug Hyung Lee
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recently, the kinase domain mutations of epidermal growth factor receptor (EGFR) gene have been identified in non–small-cell lung cancer, and these mutations have been related to the clinical response to the tyrosine kinase inhibitor gefitinib. Gefitinib treatment has also shown clinical benefits in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to explore the possibility that SCCHN harbored the EGFR mutations. Experimental Design: In this study, we analyzed EGFR gene in 41 SCCHN for the detection of the somatic mutations by PCR-single-strand conformational polymorphism analysis. Results: Overall, we detected three EGFR mutations (7.3%), and all of the mutations were the same in-frame deletion mutation in exon 19 (E746_A750del). Conclusion: These data indicated that in addition to non–small-cell lung cancer, SCCHN harbors the EGFR gene mutations, and suggested the rationale for the clinical applicability of gefinitib to SCCHN patients.
Genome-Wide Significant Association Between a Sequence Variant at 15q15.2 and Lung Cancer Risk
Authors: Thorunn Rafnar, Patrick Sulem, Soren Besenbacher, Daniel F. Gudbjartsson, Carlo Zanon, Julius Gudmundsson, Simon N. Stacey, Jelena P. Kostic, Thorgeir E. Thorgeirsson, Gudmar Thorleifsson, Hjordis Bjarnason, Halla Skuladottir, Tomas Gudbjartsson, Helgi J. Isaksson, Dolores Isla, Laura Murillo, Maria D. García-Prats, Angeles Panadero, Katja K.H. Aben, Sita H. Vermeulen, Henricus F.M. van der Heijden, William J. Feser, York E. Miller, Paul A. Bunn, Augustine Kong, Holly J. Wolf, Wilbur A. Franklin, Jose I. Mayordomo, Lambertus A. Kiemeney, Steinn Jonsson, Unnur Thorsteinsdottir, Kari Stefansson
Journal: Cancer Research (2011)

Genome-wide association studies (GWAS) have identified 3 genomic regions, at 15q24-25.1, 5p15.33, and 6p21.33, which associate with the risk of lung cancer. Large meta-analyses of GWA data have failed to find additional associations of genome-wide significance. In this study, we sought to confirm 7 variants with suggestive association to lung cancer (P < 10(-5)) in a recently published meta-analysis. In a GWA dataset of 1,447 lung cancer cases and 36,256 controls in Iceland, 3 correlated variants on 15q15.2 (rs504417, rs11853991, and rs748404) showed a significant association with lung cancer, whereas rs4254535 on 2p14, rs1530057 on 3p24.1, rs6438347 on 3q13.31, and rs1926203 on 10q23.31 did not. The most significant variant, rs748404, was genotyped in an additional 1,299 lung cancer cases and 4,102 controls from the Netherlands, Spain, and the United States and the results combined with published GWAS data. In this analysis, the T allele of rs748404 reached genome-wide significance (OR = 1.15, P = 1.1 × 10(-9)). Another variant at the same locus, rs12050604, showed association with lung cancer (OR = 1.09, 3.6 × 10(-6)) and remained significant after adjustment for rs748404 and vice versa. rs748404 is located 140 kb centromeric of the TP53BP1 gene that has been implicated in lung cancer risk. Two fully correlated, nonsynonymous coding variants in TP53BP1, rs2602141 (Q1136K) and rs560191 (E353D) showed association with lung cancer in our sample set; however, this association did not remain significant after adjustment for rs748404. Our data show that 1 or more lung cancer risk variants of genome-wide significance and distinct from the coding variants in TP53BP1 are located at 15q15.2.
Standard Chemotherapy Compared With High-Dose Chemoradiotherapy for Multiple Myeloma: Final Results of Phase III US Intergroup Trial S9321
Authors: Bart Barlogie, Robert A. Kyle, Kenneth C. Anderson, Philip R. Greipp, Hillard M. Lazarus, David D. Hurd, Jason McCoy, Dennis F. Moore, Shaker R. Dakhil, Keith S. Lanier, Robert A. Chapman, Jeana N. Cromer, Sydney E. Salmon, Brian Durie, John C. Crowley
Journal: Journal of Clinical Oncology (2006)

Results of a prospective randomized trial conducted by the Intergroupe Francais du Myélome (IFM 90) indicated that autologous hematopoietic cell-supported high-dose therapy (HDT) effected higher complete response rates and extended progression-free survival (PFS) and overall survival (OS) compared with standard-dose therapies (SDT) for patients with multiple myeloma (MM).In 1993, three North American cooperative groups launched a prospective randomized trial (S9321) comparing HDT (melphalan [MEL] 140 mg/m2 plus total-body irradiation 12 Gy) with SDT using the vincristine, carmustine, MEL, cyclophosphamide, and prednisone regimen. Responders on both arms (> or = 75%) were randomly assigned to interferon (IFN) or no maintenance treatment.With a median follow-up time of 76 months, no differences were observed in response rates between the two study arms (HDT, n = 261 patients; SDT, n = 255 patients). Similarly, PFS and OS durations did not differ between the HDT and SDT arms, with 7-year estimates of PFS of 17% and 16%, respectively, and OS of 37% and 42%, respectively. Of 242 patients achieving at least 75% tumor reduction, no difference was observed in PFS or OS among the 121 patients randomly assigned to IFN and the 121 patients randomly assigned to no maintenance therapy. Among 157 patients relapsing on SDT, 87 received a salvage autotransplantation; their median survival time of 30 months was only slightly better than the survival time of the remaining patients who were managed with further SDT (23 months; P = .13).The HDT and SDT regimens used in S9321 yielded comparable response rates and PFS and OS durations. IFN maintenance therapy did not benefit patients who achieved > or = 75% tumor reduction on either arm.
Persistent Organic Pollutants and Inflammatory Markers in a Cross-Sectional Study of Elderly Swedish People: The PIVUS Cohort
Authors: Jitender Kumar, P. Monica Lind, Samira Salihovic, Bert van Bavel, Erik Ingelsson, Lars Lind
Journal: Environmental Health Perspectives (2014)

Background: Persistent organic pollutants (POPs) are compounds that are generated through various industrial activities and released in the surrounding environment. Different animal studies have shown effects of different POPs on various inflammatory markers.Objective: Because very few studies have been conducted in humans, we assessed the associations between different POPs and inflammatory markers in a large population-based sample of elderly men and women (all 70 years of age) from Sweden.Methods: This cross-sectional study investigated the concentrations of several polychlorinated biphenyls (PCBs), organochlorine pesticides, polychlorinated dibenzo-p-dioxin, and brominated diphenyl ether congeners and their association with a number of inflammatory markers [vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E-selectin, C-reactive protein (CRP), total leucocyte count, tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and interleukin 6 (IL-6)] in 992 individuals. These individuals were recruited from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. We used a total toxic equivalency (TEQ) value that measures toxicological effects with the relative potencies of various POPs.Results: Following adjustment for potential confounders, the TEQ value (driven mainly by PCB-126) was significantly associated with levels of ICAM-1 (p < 10–5). A similar trend was also observed between sum of PCBs and VCAM-1 (p < 0.001). No significant associations were observed between levels of POPs and other inflammatory markers.Conclusions: TEQ values were associated with levels of ICAM-1, to a lesser degree also with VCAM-1, but not with CRP and several other inflammatory markers. These findings suggest an activation of vascular adhesion molecules by POPs, and particularly by PCB-126.Citation: Kumar J, Lind PM, Salihovic S, van Bavel B, Ingelsson E, Lind L. 2014. Persistent organic pollutants and inflammatory markers in a cross-sectional study of elderly Swedish people: The PIVUS cohort. Environ Health Perspect 122:977–983; http://dx.doi.org/10.1289/ehp.1307613
The cytoplasmic domains of immunoglobulin (Ig) alpha and Ig beta can independently induce the precursor B cell transition and allelic exclusion.
Authors: F Papavasiliou, M Jankovic, H Suh, M C Nussenzweig
Journal: The Journal of Experimental Medicine (1995)

In mature B cells, signals transduced through membrane immunoglobulin (Ig) produce cellular activation, yet the same receptor can also mediate deletion and silencing of autoreactive B cells. In addition, Ig expression during the antigen-independent phase of B cell development regulates the precursor B (pre-B) cell transition and allelic exclusion. To account for the diverse regulatory functions induced by membrane Ig, it has been proposed that individual receptor components have independent physiologic activities. Here we establish a role for Ig alpha in the pre-B cell transition and allelic exclusion. We find that the cytoplasmic domain of Ig alpha contains sufficient information to trigger both of these antigen-independent events. Direct comparisons of the cytoplasmic domains of Ig alpha and Ig beta show that the two are indistinguishable in the induction of the pre-B cell transition and allelic exclusion. Our experiments suggest that, despite the reported differences in certain biochemical assays, Ig alpha and Ig beta have redundant functions in the developing B cell.