tbuckley/cabot-search huggingface dataset:
Transforming Growth Factor-β <sub>1</sub> Modulates Oxidatively Modified LDL–Induced Expression of Adhesion Molecules
Authors: Hongjiang Chen, Dayuan Li, Tom Saldeen, Jawahar L. Mehta
Journal: Circulation Research (2001)

Oxidatively modified LDL (ox-LDL) activates a lectin-like receptor, LOX-1, which results in the expression of adhesion molecules on endothelial surface. We investigated the regulation of the expression of transforming growth factor-β 1 (TGF-β 1 ) and its receptors by ox-LDL and the functional significance of this interaction with regard to adhesion molecule expression in human coronary artery endothelial cells (HCAECs). Ox-LDL, in a time- and concentration-dependent manner, upregulated the expression of all 3 subtypes (1, 2, and 3 [including endoglin]) of TGF-β 1 receptors and decreased active TGF-β 1 synthesis (all P &lt;0.05 versus control and native-LDL–treated cells). Treatment of HCAECs with a monoclonal antibody to LOX-1 attenuated ox-LDL–mediated upregulation of TGF-β 1 receptors and decrease in TGF-β 1 synthesis ( P &lt;0.05 versus ox-LDL alone). Ox-LDL also enhanced the expression of P-selectin and ICAM-1 as well as monocyte adhesion to HCAECs ( P &lt;0.05 versus control untreated cells). Pretreatment with recombinant TGF-β 1 attenuated the enhanced expression of adhesion molecules and monocyte adhesion to HCAECs ( P &lt;0.05 versus ox-LDL alone). Effects of recombinant TGF-β 1 were blocked by antibody to TGF-β 1 receptor type 2, but not by antibody to endoglin. Thus ox-LDL, via activation of LOX-1, increases the expression of TGF-β 1 receptors and decreases TGF-β 1 synthesis in HCAECs. Recombinant TGF-β 1 , by binding to TGF-β 1 type 2 receptors, modulates ox-LDL–mediated expression of adhesion molecules and monocyte adhesion to HCAECs.
Genetic Evolution of T-cell Resistance in the Course of Melanoma Progression
Authors: Antje Sucker, Fang Zhao, Birgit Real, Christina Heeke, Nicola Bielefeld, Stefan Maβen, Susanne Horn, Iris Moll, Raffaela Maltaner, Peter A. Horn, Bastian Schilling, Francesco Sabbatino, Volker Lennerz, Matthias Kloor, Soldano Ferrone, Dirk Schadendorf, Christine S. Falk, Klaus Griewank, Annette Paschen
Journal: Clinical Cancer Research (2014)

CD8(+) T lymphocytes can kill autologous melanoma cells, but their activity is impaired when poorly immunogenic tumor phenotypes evolve in the course of disease progression. Here, we analyzed three consecutive melanoma lesions obtained within one year of developing stage IV disease for their recognition by autologous T cells.One skin (Ma-Mel-48a) and two lymph node (Ma-Mel-48b, Ma-Mel-48c) metastases were analyzed for T-cell infiltration. Melanoma cell lines established from the respective lesions were characterized, determining the T-cell-stimulatory capacity, expression of surface molecules involved in T-cell activation, and specific genetic alterations affecting the tumor-T-cell interaction.Metastases Ma-Mel-48a and Ma-Mel-48b, in contrast with Ma-Mel-48c, were infiltrated by T cells. The T-cell-stimulatory capacity was found to be strong for Ma-Mel-48a, lower for Ma-Mel-48b, and completely abrogated for Ma-Mel-48c cells. The latter proved to be HLA class I-negative due to an inactivating mutation in one allele of the beta-2-microglobulin (B2M) gene and concomitant loss of the other allele by a deletion on chromosome 15q. The same deletion was already present in Ma-Mel-48a and Ma-Mel-48b cells, pointing to an early acquired genetic event predisposing to development of β2m deficiency. Notably, the same chronology of genetic alterations was also observed in a second β2m-deficient melanoma model.Our study reveals a progressive loss in melanoma immunogenicity during the course of metastatic disease. The genetic evolvement of T-cell resistance suggests screening tumors for genetic alterations affecting immunogenicity could be clinically relevant in terms of predicting patient responses to T-cell-based immunotherapy.
Serum from patients with SLE instructs monocytes to promote IgG and IgA plasmablast differentiation
Authors: HyeMee Joo, Christine Coquery, Yaming Xue, Ingrid Gayet, Stacey R. Dillon, Marilynn Punaro, Gerard Zurawski, Jacques Banchereau, Virginia Pascual, SangKon Oh
Journal: The Journal of Experimental Medicine (2012)

The development of autoantibodies is a hallmark of systemic lupus erythematosus (SLE). SLE serum can induce monocyte differentiation into dendritic cells (DCs) in a type I IFN–dependent manner. Such SLE-DCs activate T cells, but whether they promote B cell responses is not known. In this study, we demonstrate that SLE-DCs can efficiently stimulate naive and memory B cells to differentiate into IgG- and IgA-plasmablasts (PBs) resembling those found in the blood of SLE patients. SLE-DC–mediated IgG-PB differentiation is dependent on B cell–activating factor (BAFF) and IL-10, whereas IgA-PB differentiation is dependent on a proliferation-inducing ligand (APRIL). Importantly, SLE-DCs express CD138 and trans-present CD138-bound APRIL to B cells, leading to the induction of IgA switching and PB differentiation in an IFN-α–independent manner. We further found that this mechanism of providing B cell help is relevant in vivo, as CD138-bound APRIL is expressed on blood monocytes from active SLE patients. Collectively, our study suggests that a direct myeloid DC–B cell interplay might contribute to the pathogenesis of SLE.
A unique natural human IgG antibody with anti-alpha-galactosyl specificity.
Authors: U Galili, E A Rachmilewitz, A Peleg, I Flechner
Journal: The Journal of Experimental Medicine (1984)

A new natural anti-alpha-galactosyl IgG antibody (anti-Gal) was found to be present in high titer in the serum of every normal individual studied. The antibody was isolated by affinity chromatography on a melibiose-Sepharose column. The reactivity of the antibody was assessed by its interaction with alpha-galactosyl residues on rabbit erythrocytes (RabRBC). The specificity was determined by inhibition experiments with various carbohydrates. The anti-Gal interacts with alpha-galactosyl residues, possibly on glycolipids of human RBC (HuRBC), after removal of membrane proteins by treatment with pronase. In addition, the anti-Gal bind specifically to normal and pathologically senescent HuRBC, suggesting a physiological role for this natural antibody in the aging of RBC. The ubiquitous presence of anti-Gal in high titers throughout life implies a constant antigenic stimulation. In addition to the theoretical interest in the antibody, the study of the anti-Gal reactivity seems to bear immunodiagnostic significance. Decrease in the antibody titer was found to reflect humoral immunodeficiency disorders.
Intestinal failure defined by measurements of intestinal energy and wet weight absorption
Authors: P B Jeppesen
Journal: Gut (2000)

Intestinal failure defined by the minimal energy and wet weight absorption required to avoid home parenteral nutrition (HPN) is not well described. Thus the aim of this study was to identify the minimal level of gut function necessary to avoid parenteral support using objective measurements of intestinal function.Energy (bomb calorimetry) and wet weight absorption were measured during 48 hour balance studies in 45 HPN patients with intestinal failure and in 44 non-HPN borderline patients with a short bowel or malabsorption exceeding 2 MJ/day.In the non-HPN patients, the lower 5% confidence interval of the absorption of energy was 84% of the basal metabolic rate (BMR, the Harris-Benedict equations), equivalent to 4.9 MJ/day. Wet weight absorption was 1.4 kg/day. The HPN patients absorbed less of either or both. The non-HPN patients absorbed 24-86% (range) of the energy and 23-95% of the wet weight. Absorption in the HPN patients ranged from below 0% (net secretion) in patients with very short bowels to 100% absorption of an insufficient oral intake in patients with pseudo-obstruction. Non-HPN patients who absorbed less than half of their intake avoided HPN by hyperphagia (200-400% of BMR equivalent to 10-24 MJ/day, and 3-7 kg/day of wet weight).Intestinal failure was accurately measured as absorption below 1.4 kg/day of wet weight and 84% of the calculated BMR (depending on weight, sex and age), which is equal to 4.9 MJ/day. Intestinal absorption, expressed as a percentage of intake, did not discriminate between patients with and without intestinal failure, except for patients who absorbed less than 25% of their intake.
The FANTOM web resource: from mammalian transcriptional landscape to its dynamic regulation
Authors: Hideya Kawaji, Jessica Severin, Marina Lizio, Andrew Waterhouse, Shintaro Katayama, Katharine M Irvine, David A Hume, Alistair RR Forrest, Harukazu Suzuki, Piero Carninci, Yoshihide Hayashizaki, Carsten O Daub
Journal: Genome biology (2009)

In FANTOM4, an international collaborative research project, we collected a wide range of genome-scale data, including 24 million mRNA 5'-reads (CAGE tags) and microarray expression profiles along a differentiation time course of the human THP-1 cell line and under 52 systematic siRNA perturbations. In addition, data regarding chromatin status derived from ChIP-chip to elucidate the transcriptional regulatory interactions are included. Here we present these data to the research community as an integrated web resource.
Estimating Gene Gain and Loss Rates in the Presence of Error in Genome Assembly and Annotation Using CAFE 3
Authors: Mira V. Han, Gregg W.C. Thomas, Jose Lugo-Martinez, Matthew W. Hahn
Journal: Molecular Biology and Evolution (2013)

Current sequencing methods produce large amounts of data, but genome assemblies constructed from these data are often fragmented and incomplete. Incomplete and error-filled assemblies result in many annotation errors, especially in the number of genes present in a genome. This means that methods attempting to estimate rates of gene duplication and loss often will be misled by such errors and that rates of gene family evolution will be consistently overestimated. Here, we present a method that takes these errors into account, allowing one to accurately infer rates of gene gain and loss among genomes even with low assembly and annotation quality. The method is implemented in the newest version of the software package CAFE, along with several other novel features. We demonstrate the accuracy of the method with extensive simulations and reanalyze several previously published data sets. Our results show that errors in genome annotation do lead to higher inferred rates of gene gain and loss but that CAFE 3 sufficiently accounts for these errors to provide accurate estimates of important evolutionary parameters.
Whole-body FDG-PET versus Tc-99m MDP bone scintigraphy for detection of bone metastases in patients with lung cancer
Authors: M. Tian, H. Zhang, K. Endo
Journal: Journal of Clinical Oncology (2005)

2023 Background: Lung caner is the most common cancer in the world accounts for 12.3% of all new cancer cases with millions of deaths per year. For the prognosis and the therapy strategies, the evaluation of tumor spread is important. Recently, 18F-2-fluro-deoxy-D-glucose (FDG) positron emission tomography (PET) is used to detect local and distant metastases. The aim of this study was to evaluate the effect of adding whole body FDG PET to conventional bone scintigraphy for staging and detection bone metastasis in patients with lung cancer. Methods: We evaluated and compared the results of both FDG PET and bone scintigraphy in 132 lung cancer patients who had suspected local or distance metastases before treatment. Bone scintigraphy and FDG PET was performed blinded to the findings of history and physical examination. The combined results of magnetic resonance imaging (MRI), computed tomography (CT) and the subsequent clinical course served as the gold standard for the identification of bone metastases. Results: Bone scintigraphy showed a sensitivity of 87% and FDG PET was 96% in detection of bone metastases. Without the findings of bone scintigraphy and the gold standard methods, 14–22% of patients would have undergone unnecessary surgery or neoadjuvant therapy. The addition of a PET scan to a bone scintigraphy allowed for more precise localization of the lesions in some patients. Conclusion: The addition of FDG PET to the standard bone scan is useful to detect the unexpected distant bone metastases, and give more information to the local and distant metastases. Abnormal PET findings should be confirmed to prevent patients from being denied appropriate treatment. No significant financial relationships to disclose.
Beta lactam plus macrolide antibiotic combination therapy reduces the mortality of community-acquired pneumococcal pneumonia more than beta lactam antibiotics alone
Authors: Akihiro Ito, Tadashi Ishida, Hiromasa Tachibana, Akihiro Nishiyama, Kenjiro Furuta, Maki Tanaka, Fumiaki Tokioka, Hiroshige Yoshioka, Machiko Arita, Toru Hashimoto
Journal: European Respiratory Journal (2014)

Background  Some papers have reported that combination therapy with beta lactam and macrolide antibiotics (combination therapy) reduces the mortality of severe community-acquired pneumococcal pneumonia with bacteremia or that requiring mechanical ventilation more than therapy with beta lactam antibiotics alone (monotherapy). However, in Japan, the effect of macrolide antibiotics in pneumococcal pneumonia remains unclear.   Objective  To determine whether combination therapy is able to reduce mortality in patients with community-acquired pneumococcal pneumonia.   Materials and methods  The data of community-acquired pneumococcal pneumonia patients hospitalized in Kurashiki Central Hospital between February 2001 and November 2013 were analyzed. Patients9 charts were retrospectively analyzed to determine whether combination therapy reduced mortality in patients with community-acquired pneumococcal pneumonia more than monotherapy. The patients were divided into severe and non-severe pneumonia groups according to the ATS/IDSA criteria for severe pneumonia.   Results  A total of 539 patients (360 males, 179 females; mean age, 71.1 years) were studied. The mortality rates were 5.1% (23/455) with monotherapy and 2.4% (2/84) with combination therapy. In patients with severe pneumonia, the mortality rates were lower with combination therapy (8.7%, 2/23) than with monotherapy (19.6%, 21/107).   Conclusion  Severe pneumococcal pneumonia should be treated with beta lactam plus macrolide antibiotic combination therapy to achieve a better prognosis than with beta lactam monotherapy.
Health information systems in Africa: descriptive analysis of data sources, information products and health statistics
Authors: Peter Ebongue Mbondji, Derege Kebede, Edoh William Soumbey-Alley, Chris Zielinski, Wenceslas Kouvividila, Paul-Samson Lusamba-Dikassa
Journal: Journal of the Royal Society of Medicine (2014)

To identify key data sources of health information and describe their availability in countries of the World Health Organization (WHO) African Region.An analytical review on the availability and quality of health information data sources in countries; from experience, observations, literature and contributions from countries.Forty-six Member States of the WHO African Region.No participants.The state of data sources, including censuses, surveys, vital registration and health care facility-based sources.In almost all countries of the Region, there is a heavy reliance on household surveys for most indicators, with more than 121 household surveys having been conducted in the Region since 2000. Few countries have civil registration systems that permit adequate and regular tracking of mortality and causes of death. Demographic surveillance sites function in several countries, but the data generated are not integrated into the national health information system because of concerns about representativeness. Health management information systems generate considerable data, but the information is rarely used because of concerns about bias, quality and timeliness. To date, 43 countries in the Region have initiated Integrated Disease Surveillance and Response.A multitude of data sources are used to track progress towards health-related goals in the Region, with heavy reliance on household surveys for most indicators. Countries need to develop comprehensive national plans for health information that address the full range of data needs and data sources and that include provision for building national capacities for data generation, analysis, dissemination and use.
Delayed Nausea and Vomiting Continue to Reduce Patients' Quality of Life After Highly and Moderately Emetogenic Chemotherapy Despite Antiemetic Treatment
Authors: Brigitte Bloechl-Daum, Robert R. Deuson, Panagiotis Mavros, Mogens Hansen, Jørn Herrstedt
Journal: Journal of Clinical Oncology (2006)

Purpose Chemotherapy-induced nausea and vomiting (CINV) are major adverse effects of cancer chemotherapy. We compared the impact of acute (during the first 24 hours postchemotherapy) and delayed (days 2 through 5 postchemotherapy) CINV on patients' quality of life (QoL) after highly or moderately emetogenic chemotherapy (HEC and MEC, respectively). Patients and Methods This prospective, multicenter, multinational study was conducted in 14 medical practices on cancer patients undergoing either HEC or MEC treatment. Patients recorded episodes of nausea and vomiting in a diary. Patients completed the Functional Living Index-Emesis (FLIE) questionnaire at baseline and on day 6. Results A total of 298 patients were assessable (67 HEC patients, 231 MEC patients). Emesis was reported by 36.4% of patients (13.2% acute, 32.5% delayed) and nausea by 59.7% (36.2% acute, 54.3% delayed). HEC patients reported significantly lower mean FLIE total score than MEC patients (95.5 v 107.8 respectively; P = .0049). Among all patients, the nausea score was significantly lower than the vomiting score (50.0 and 55.3, respectively; P = .0097). Of the 173 patients who experienced neither vomiting nor nausea during the first 24 hours postchemotherapy, 22.9% reported an impact of CINV on daily life caused by delayed CINV. Conclusion CINV continues to adversely affect patients' QoL despite antiemetic therapy even after treatment with only moderately emetogenic chemotherapy regimens, and even in the subgroup of patients who do not experience nausea and vomiting during the first 24 hours. On the basis of the FLIE results in this study, nausea had a stronger negative impact on patients' daily lives than vomiting.
Diet and Risk of Colorectal Adenomas: Macronutrients, Cholesterol, and Fiber
Authors: R. S. Sandler, C. M. Lyles, L. A. Peipins, C. A. McAuliffe, J. T. Woosley, L. L. Kupper
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Diet and Risk of Colorectal Adenomas: Macronutrients, Cholesterol, and Fiber Get access Robert S. Sandler, Robert S. Sandler Division of Digestive Diseases and Nutrition, Department of Medicine, and the Center for Gastrointestinal Biology and DiseaseChapel Hill Correspondence to : Rober S. Sandler, M.D., Division of Digestive Diseases and Nutrition, CB #7080, 423A Burnett-Womack Bldg., University of North Carolina, Chapel Hill, NC 27599-7080. Search for other works by this author on: Oxford Academic PubMed Google Scholar Cynthia M. Lyles, Cynthia M. Lyles Department of BiostatisticsChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar Lucy A. Peipins, Lucy A. Peipins Department of EpidemiologyChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar Colleen A. McAuliffe, Colleen A. McAuliffe Division of Digestive Diseases and Nutrition, Department of MedicineChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar John T. Woosley, John T. Woosley Department of Pathology, University of North CarolinaChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar Lawrence L. Kupper Lawrence L. Kupper Department of BiostatisticsChapel Hill Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 11, 2 June 1993, Pages 884–891, https://doi.org/10.1093/jnci/85.11.884 Published: 02 June 1993 Article history Received: 07 August 1992 Accepted: 03 February 1993 Published: 02 June 1993
Salivary contribution to exhaled nitric oxide
Authors: W. Zetterquist, C Pedroletti, J.O.n. Lundberg, K. Alving
Journal: European Respiratory Journal (1999)

Dietary and metabolic nitrate is distributed from the blood to the saliva by active uptake in the salivary glands, and is reduced to nitrite in the oral cavity by the action of certain bacteria. Since it has been reported that nitric oxide may be formed nonenzymatically from nitrite this study aimed to determine whether salivary nitrite could influence measurements of exhaled NO. Ten healthy subjects fasted overnight and ingested 400 mg potassium nitrate, equivalent to approximately 200 g spinach. Exhaled NO and nasal NO were regularly measured with a chemiluminescence technique up to 3 h after the ingestion. Measurements of exhaled NO were performed with a single-breath procedure, standardized to a 20-s exhalation, at a flow of 0.15 L x s(-1), and oral pressure of 8-10 cmH2O. Values of NO were registered as NO release rate (pmol x s(-1)) during the plateau of exhalation. Exhaled NO increased steadily over time after nitrate load and a maximum was seen at 120 min (77.0+/-15.2 versus 31.2+/-3.0 pmol x s(-1), p&lt;0.01), whereas no increase was detected in nasal NO levels. Salivary nitrite concentrations increased in parallel; at 120 min there was a four-fold increase compared with baseline (1.56+/-0.44 versus 0.37+/-0.09 mM, p&lt;0.05). The nitrite-reducing conditions in the oral cavity were also manipulated by the use of different mouthwash procedures. The antibacterial agent chlorhexidine acetate (0.2%) decreased NO release by almost 50% (p&lt;0.01) 90 min after nitrate loading and reduced the preload control levels by close to 30% (p&lt;0.05). Sodium bicarbonate (10%) also reduced exhaled NO levels, but to a somewhat lesser extent than chlorhexidine acetate. In conclusion, salivary nitric oxide formation contributes to nitric oxide in exhaled air and a large intake of nitrate-rich foods before the investigation might be misinterpreted as an elevated inflammatory activity in the airways. This potential source of error and the means for avoiding it should be considered in the development of a future standardized method for measurements of exhaled nitric oxide.