tbuckley/cabot-search huggingface dataset:
Abstract 5192: Mutational analysis of primary central nervous system lymphoma
Authors: Aurélie Bruno, Blandine Boisselier, Karim Labreche, Yannick Marie, Marc Polivka, Anne Jouvet, Clovis Adam, Dominique Figarella-Branger, Catherine Miquel, Anne Vital, Caroline Houillier, Carole Soussain, Karima Mokhtari, Romain Daveau, Khê Hoang-Xuan
Journal: Cancer Research (2014)

Abstract Background: Primary central nervous system lymphoma (PCNSL) is a rare extranodal diffuse large B-cell lymphoma (DLBCL). Little is known about the genomic basis of tumorigenesis in PCNSL partly explained by the rarity of biological material available for research studies. PCNSL patients display poor outcomes compared to systemic DLBCL and it is still unclear whether this is linked to the organ-specific microenvironment or reflects a specific, aggressive, intrinsic biological behavior. To our knowledge, the mutational landscape of PCNSL has never been investigated Experimental design: We analyzed 9 paired tumor and germline DNA samples from PCNSL patients by high throughput exome sequencing. Then, we performed focused sequencing in 28 additional PCNSL tumors to validate somatic genomic alterations and better estimate their incidence. Mutational data were correlated with copy number variations (CNV) identified by SNP and CGH arrays and clinical data. Results: We identified recurrent somatic mutations in genes involved in key signalling pathways such as NFκB (i.e. MYD88, CD79B, TBL1XR1), B cell differentiation (i.e. ETV6, EBF1, IRF4) and cell cycle control (i.e. BTG1, PIM1). We found somatic mutations on MYD88 (38%), CD79B (30%), TBL1XR1 (22%) or ETV6 (16%) genes and described bi-allelic inactivation of TBL1XR1 and ETV6 genes. Interestingly, the correlation with the outcome showed a significant negative impact of TBL1XR1 mutation on survival in a multivariate analysis. Conclusions: The present study showed that PCNSLs have high genetic heterogeneity and that their mutational patterns display similarities with extracerebral DLBCL, particularly of the ABC subtype, suggesting shared underlying biological mechanisms. These results provide new insights into the mutational landscape of PCNSL and potential targets for therapeutic strategies. This work benefited from the LOC study group network (réseau national de centres experts des lymphomes primitifs du SNC, INCa). Citation Format: Aurélie Bruno, Blandine Boisselier, Karim Labreche, Yannick Marie, Marc Polivka, Anne Jouvet, Clovis Adam, Dominique Figarella-Branger, Catherine Miquel, Anne Vital, Caroline Houillier, Carole Soussain, Karima Mokhtari, Romain Daveau, Khê Hoang-Xuan. Mutational analysis of primary central nervous system lymphoma. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5192. doi:10.1158/1538-7445.AM2014-5192
Acute safety and effects on mucociliary clearance of aerosolized uridine 5'-triphosphate +/- amiloride in normal human adults.
Authors: K N Olivier, W D Bennett, K W Hohneker, K L Zeman, L J Edwards, R C Boucher, M R Knowles
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

Impaired mucociliary clearance contributes to the pathophysiology of several airways diseases including cystic fibrosis, asthma, and chronic bronchitis. Extracellular triphosphate nucleotides (adenosine 5'-triphosphate [ATP], uridine 5'-triphosphate [UTP]) activate several components of the mucociliary escalator, suggesting they may have potential as therapeutic agents for airways diseases. We conducted initial (Phase I) studies of acute safety and efficacy of aerosolized UTP alone and in combination with aerosolized amiloride, the sodium channel blocker, in normal human volunteers. Safety was assessed by measurement of pulmonary function. Neither UTP alone nor in combination with amiloride caused any clinically significant adverse effects on airway mechanics, (subdivisions of) lung volumes, or gas exchange. Acute efficacy of UTP and amiloride alone and in combination, was assessed by measuring changes in the clearance of inhaled radiolabeled particles. A 2.5-fold increase in mucociliary clearance was seen in response to UTP alone and in combination with amiloride. We conclude that aerosolized UTP +/- amiloride clearly enhances mucociliary clearance without acute adverse effects in normal adults, and may have therapeutic potential to enhance airways clearance in diseases characterized by retained airways secretions.
Gastroscopic Morphology of Benign Gastric Ulcer: Results of a follow-up study by cinegastroscopy
Authors: G. Clémençon
Journal: Endoscopy (1970)

This is a report on cinegastroscopic investigations on 73 patients suffering from gastric ulcer. A circular capillary system around the ulcer is described and its possible significance for benignity and healing of ulcer is discussed. In ten out of 24 patients deformity of the gastric cavity still was recognizable five months later. Edema of the ulcer margin was often impressive. Ten patients suffered from or had signs of a healed duodenal ulcer. Eighteen patients had atrophy of the mucosa in the lower portion of the stomach. In 17 cases the pyloric channel was deformed and regurgitation of duodenal contents was observed in eight by gastroscopy. These observations are discussed in connection with newer pathogenetic concepts in the etiology of gastric ulcer. Some of the described results do not seem to have been subject of previous reports. The value of cinegastroscopy is emphasized.
Sorafenib Blocks the RAF/MEK/ERK Pathway, Inhibits Tumor Angiogenesis, and Induces Tumor Cell Apoptosis in Hepatocellular Carcinoma Model PLC/PRF/5
Authors: Li Liu, Yichen Cao, Charles Chen, Xiaomei Zhang, Angela McNabola, Dean Wilkie, Scott Wilhelm, Mark Lynch, Christopher Carter
Journal: Cancer Research (2006)

Angiogenesis and signaling through the RAF/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK cascade have been reported to play important roles in the development of hepatocellular carcinomas (HCC). Sorafenib (BAY 43-9006, Nexavar) is a multikinase inhibitor with activity against Raf kinase and several receptor tyrosine kinases, including vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor (PDGFR), FLT3, Ret, and c-Kit. In this study, we investigated the in vitro effects of sorafenib on PLC/PRF/5 and HepG2 HCC cells and the in vivo antitumor efficacy and mechanism of action on PLC/PRF/5 human tumor xenografts in severe combined immunodeficient mice. Sorafenib inhibited the phosphorylation of MEK and ERK and down-regulated cyclin D1 levels in these two cell lines. Sorafenib also reduced the phosphorylation level of eIF4E and down-regulated the antiapoptotic protein Mcl-1 in a MEK/ERK-independent manner. Consistent with the effects on both MEK/ERK-dependent and MEK/ERK-independent signaling pathways, sorafenib inhibited proliferation and induced apoptosis in both HCC cell lines. In the PLC/PRF/5 xenograft model, sorafenib tosylate dosed at 10 mg/kg inhibited tumor growth by 49%. At 30 mg/kg, sorafenib tosylate produced complete tumor growth inhibition. A dose of 100 mg/kg produced partial tumor regressions in 50% of the mice. In mechanism of action studies, sorafenib inhibited the phosphorylation of both ERK and eIF4E, reduced the microvessel area (assessed by CD34 immunohistochemistry), and induced tumor cell apoptosis (assessed by terminal deoxynucleotidyl transferase-mediated nick end labeling) in PLC/PRF/5 tumor xenografts. These results suggest that the antitumor activity of sorafenib in HCC models may be attributed to inhibition of tumor angiogenesis (VEGFR and PDGFR) and direct effects on tumor cell proliferation/survival (Raf kinase signaling-dependent and signaling-independent mechanisms).
Stumbling into rationing
Authors: R. Smith
Journal: BMJ (1999)

Muddling through is the British way. While some countries may tackle a problem like the rationing of health care head on—admitting the problem at the highest level, analysing it, declaring their values, and beginning work on a just, transparent solution—the British deny the problem and nibble at its edges. Surely we can do better. This government, like the last, avoids the word rationing, but it knows that not everything can be done for everybody. So it has constructed machinery with Orwellian names—health improvement plans and the National Centre for …
A prospective cohort study of the incidence of injuries among junior Australian football players: evidence for an effect of playing-age level
Authors: M Romiti, C F Finch, B Gabbe
Journal: British Journal of Sports Medicine (2007)

Objective: To determine the rate of injury in junior Australian football, and to describe the patterns and severity of these injuries across nine levels of play (U9 to U18). Design: Prospective cohort study. Setting: Junior Australian football games and training sessions were observed for 54 teams from New South Wales and Victoria over the 2004 playing season. Participants: Six teams from each level of play were invited to participate in the study. Overall, data were collected for 51 teams over 40 208 hours of player exposure. Independent variables: Participation and injury data were collected prospectively. Main outcome measures: Injury was defined as “any trauma that causes some disability or pain”. Injury severity was identified by the action of players immediately after the injury event. Results: The overall injury rate was 18.0 (95% CI 16.6 to 19.3) injuries per 1000 player hours. The main cause of injury was body contact (67.3%). There was an increased frequency of sprains and strains, and injury severity with increasing level of play. The rates of injury for players who stayed off the field (6.4 injuries per 1000 hours, 95% CI 5.6 to 7.2) or were advised to seek off-field medical advice (5.0 injuries per 1000 hours, 95% CI 4.3 to 5.7) were low. Conclusion: Compared with the adult game, junior Australian football is relatively safe. However, injury rates increase as children progress across age-determined levels of play towards the more adult form of the game.
Effect of amiodarone on mortality after myocardial infarction: A double-blind, placebo-controlled, pilot study
Authors: Leszek Ceremuzynski, Elzbieta Kleczar, Maria Krzeminska-Pakula, Jerzy Kuch, Edmund Nartowicz, Jadwiga Smielak-Korombel, Andrzej Dyduszynski, Jerzy Maciejewicz, Teresa Zaleska, Elzbieta Lazarczyk-Kedzia, Janina Motyka, Barbara Paczkowska, Olga Sczaniecka, Salim Yusuf
Journal: Journal of the American College of Cardiology (1992)
Relationships among Polycyclic Aromatic Hydrocarbon–DNA Adducts, Proximity to the World Trade Center, and Effects on Fetal Growth
Authors: Frederica P. Perera, Deliang Tang, Virginia Rauh, Kristin Lester, Wei Yann Tsai, Yi Hsuan Tu, Lisa Weiss, Lori Hoepner, Jeffrey King, Giuseppe Del Priore, Sally Ann Lederman
Journal: Environmental Health Perspectives (2005)

Polycyclic aromatic hydrocarbons (PAHs) are toxic pollutants released by the World Trade Center (WTC) fires and various urban combustion sources. Benzo[a]pyrene (BaP) is a representative member of the class of PAHs. PAH-DNA adducts, or BaP-DNA adducts as their proxy, provide a measure of chemical-specific genetic damage that has been associated with increased risk of adverse birth outcomes and cancer. To learn whether PAHs from the WTC disaster increased levels of genetic damage in pregnant women and their newborns, we analyzed BaP-DNA adducts in maternal (n = 170) and umbilical cord blood (n = 203) obtained at delivery from nonsmoking women who were pregnant on 11 September 2001 and were enrolled at delivery at three downtown Manhattan hospitals. The mean adduct levels in cord and maternal blood were highest among newborns and mothers who resided within 1 mi of the WTC site during the month after 11 September, intermediate among those who worked but did not live within this area, and lowest in those who neither worked nor lived within 1 mi (reference group). Among newborns of mothers living within 1 mi of the WTC site during this period, levels of cord blood adducts were inversely correlated with linear distance from the WTC site (p = 0.02). To learn whether PAHs from the WTC disaster may have affected birth outcomes, we analyzed the relationship between these outcomes and DNA adducts in umbilical cord blood, excluding preterm births to reduce variability. There were no independent fetal growth effects of either PAH-DNA adducts or environmental tobacco smoke (ETS), but adducts in combination with in utero exposure to ETS were associated with decreased fetal growth. Specifically, a doubling of adducts among ETS-exposed subjects corresponded to an estimated average 276-g (8%) reduction in birth weight (p = 0.03) and a 1.3-cm (3%) reduction in head circumference (p = 0.04). The findings suggest that exposure to elevated levels of PAHs, indicated by PAH-DNA adducts in cord blood, may have contributed to reduced fetal growth in women exposed to the WTC event.
Diagnosis, Microbial Epidemiology, and Antibiotic Treatment of Acute Otitis Media in Children
Authors: Tumaini R. Coker, Linda S. Chan, Sydne J. Newberry, Mary Ann Limbos, Marika J. Suttorp, Paul G. Shekelle, Glenn S. Takata
Journal: JAMA (2010)

Acute otitis media (AOM) is the most common condition for which antibiotics are prescribed for US children; however, wide variation exists in diagnosis and treatment.To perform a systematic review on AOM diagnosis, treatment, and the association of heptavalent pneumococcal conjugate vaccine (PCV7) use with AOM microbiology.PubMed, Cochrane Databases, and Web of Science, searched to identify articles published from January 1999 through July 2010.Diagnostic studies with a criterion standard, observational studies and randomized controlled trials comparing AOM microbiology with and without PCV7, and randomized controlled trials assessing antibiotic treatment.Independent article review and study quality assessment by 2 investigators with consensus resolution of discrepancies.Of 8945 citations screened, 135 were included. Meta-analysis was performed for comparisons with 3 or more trials. Few studies examined diagnosis; otoscopic findings of tympanic membrane bulging (positive likelihood ratio, 51 [95% confidence interval {CI}, 36-73]) and redness (positive likelihood ratio, 8.4 [95% CI, 7-11]) were associated with accurate diagnosis. In the few available studies, prevalence of Streptococcus pneumoniae decreased (eg, 33%-48% vs 23%-31% of AOM isolates), while that of Haemophilus influenzae increased (41%-43% vs 56%-57%) pre- vs post-PCV7. Short-term clinical success was higher for immediate use of ampicillin or amoxicillin vs placebo (73% vs 60%; pooled rate difference, 12% [95% CI, 5%-18%]; number needed to treat, 9 [95% CI, 6-20]), while increasing the rate of rash or diarrhea by 3% to 5%. Two of 4 studies showed greater clinical success for immediate vs delayed antibiotics (95% vs 80%; rate difference, 15% [95% CI, 6%-24%] and 86% vs 70%; rate difference, 16% [95% CI, 6%-26%]). Data are absent on long-term effects on antimicrobial resistance. Meta-analyses in general showed no significant differences in antibiotic comparative effectiveness.Otoscopic findings are critical to accurate AOM diagnosis. AOM microbiology has changed with use of PCV7. Antibiotics are modestly more effective than no treatment but cause adverse effects in 4% to 10% of children. Most antibiotics have comparable clinical success.
Infectious Diseases of the Fetus and Newborn Infant
Authors: Leslie L. Barton
Journal: JAMA (1995)

The fourth edition of<i>Infectious Diseases of the Fetus and Newborn Infant</i>is visual testimony to the "growth and development" of the field of perinatal infectious diseases. Although one would wish to compare it to similar texts, there are none. The infectious diseases therein may virtually all be found in Feigin and Cherry's<i>Textbook of Pediatric Infectious Diseases</i>but with neither the depth nor perinatal focus. Thus, the only real comparison for Remington and Klein's treatise is with its own previous editions published over the last 18 years. During this time, the chapters have grown from 20 to 35 in number. Fifteen contributors alone have been added since the last edition, which was published in 1990. All along, the editors have consistently produced a "complete, critical and contemporary review of infections of the fetus and newborn." The scope has continually broadened to include well-organized discussions of the pathophysiology, epidemiology, diagnosis,
Patient Protection and Affordable Care Act: Promise and Peril for Primary Care
Authors: John D. Goodson
Journal: Annals of Internal Medicine (2010)

The Patient Protection and Affordable Care Act (PPACA) of 2010 brings both promise and peril for primary care. This Act has the potential to reestablish primary care as the foundation of U.S. health care delivery. The legislation authorizes specific programs to stabilize and expand the primary care physician workforce, provides an immediate 10% increase in primary care physician payment, creates an opportunity to correct the skewed resource-based relative value scale, and supports innovation in primary care practice. Nevertheless, the peril is that the PPACA initiatives may not alter the current trend toward an increasingly specialized physician workforce. To realize the potential for the PPACA to achieve a more equitable balance between generalist and specialist physicians, all primary care advocates must actively engage in the long rebuilding process.
Abstract 5485: Apoptosis-targeted cell and drug delivery to tumor.
Authors: Lianhua Chi, Napoleon Bonaparte, Rang-woon Park, In-san Kim, Byung-heon Lee
Journal: Cancer Research (2013)

Abstract When tumor cells undergo apoptosis in response to chemotherapy, the levels of apoptotic biomarkers such as phosphatidylserine and histone H1 are increased at the cell surface. Here we hypothesized that the chemotherapy-induced apoptosis would amplify in situ apoptotic biomarkers (homing signals) for apoptosis-targeted drug carriers and enhance drug delivery. To examine this possibility, we employed a phage display-identified CQRPPR peptide (ApoPep-1) as a targeting moiety, which was able to recognize apoptotic cells by binding to histone H1 on the surface of apoptotic cells. When injected into tumor-bearing mice, ApoPep-1-labeled, fluorescent liposomes containing doxorubicin inhibited tumor growth more efficiently than untargeted or folate-labeled liposomes. Moreover, in vivo fluorescence imaging could enable monitoring of tumor response during the chemotherapy. The imaging signals at tumor were increased by the homing of apoptosis-targeted liposomes, which was correlated with the increase of apoptosis and the amount of doxorubicin (payloads) at the tumor and, conversely, with the decrease of tumor volume. Next, we harnessed the chemotherapy-induced apoptosis of tumor cells as a homing signal for the delivery of apoptosis-targeted T cells to tumor. When labeled with ApoPep-1 using an oleyl acid-derived membrane anchor, targeted T cells preferentially bound to apoptotic tumor cells over living cells. In vivo imaging showed higher levels of tumor homing of targeted, fluorescent T cells in mice treated with chemotherapy more than those of untargeted T cells. These results demonstrate that the apoptosis-targeted delivery can efficiently enhance the delivery of cells or drugs to tumor and, when combined with imaging of apoptosis, provides a real-time monitoring of tumor response for cancer theragnosis. Citation Format: Lianhua Chi, Napoleon Bonaparte, Rang-woon Park, In-san Kim, Byung-heon Lee. Apoptosis-targeted cell and drug delivery to tumor. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5485. doi:10.1158/1538-7445.AM2013-5485
INITIAL CLINICAL EXPERIENCE WITH IN-111 SATUMOMAB PENDETIDE (ONCOSCINT CR/OV) AT MD ANDERSON CANCER CENTER
Authors: E. S. Delpassand, V. A. Bhadkamkar, T. P. Haynie, Jose R. Garcia, Donald A. Podoloff
Journal: Clinical Nuclear Medicine (1994)

Delpassand, E. S. M.D.; Bhadkamkar, V. A. M.Sc., M.S.; Haynie, T. P. M.D.; Garcia, Jose R. M.D.; Podoloff, Donald A. M.D., UT M.D. Author Information
Systemic sclerosis: current pathogenetic concepts and future prospects for targeted therapy
Authors: C.P. Denton, C.M. Black, J.H. Korn, B. de Crombrugghe
Journal: The Lancet (1996)

Although there is no cure for systemic sclerosis, the disease is certainly treatable. And the more that is understood of its pathogenesis, the better the prospects for treatment. Excessive collagen deposition in the skin and viscera is responsible for the morbidity and mortality. The immune system plays a critical role in setting up the fibrotic process, but impaired regulation of collagen gene expression probably underlies the persistence of fibrosis. The development of effective antifibrotic drugs, in particular agents that inhibit transcription factors involved in the activation of type I collagen genes, is likely to be the way forward for treatment of the later stages of diffuse systemic sclerosis, with immunomodulatory therapy for the earlier stages.
Subcellular characteristics of phospholipase A2 activity in the rat kidney. Enhanced cytosolic, mitochondrial, and microsomal phospholipase A2 enzymatic activity after renal ischemia and reperfusion.
Authors: H Nakamura, R A Nemenoff, J H Gronich, J V Bonventre
Journal: Journal of Clinical Investigation (1991)

Phospholipase A2 (PLA2) activities in cytosolic, mitochondrial, and microsomal fractions of rat kidneys were characterized under control conditions, after ischemia, and subsequent to ischemia and reperfusion. Two forms of PLA2 activity were present in the cytosolic fraction: a high molecular weight form, active against phosphatidylcholine (PC), and phosphatidylethanolamine (PE), which upon purification has a molecular mass of 110 kD; and smaller form (Mr approximately 14 kD), active against PE. In mitochondrial and microsomal fractions a single form (Mr approximately 14 kD), active against both PC and PE, was dominant. Activities in each fraction were optimal at pH 8.5-9.5. Cytosolic PLA2 activity was enhanced when Ca2+ concentration [( Ca2+]) was increased over the range of 10(-7) to 10(-6) M. Mitochondrial PLA2 activity required higher [Ca2+] for activation (greater than 10(-6) M). After 45 min of ischemia cytosolic PLA2 activity was decreased, whereas mitochondrial and microsomal activities were increased. When ischemia was followed by 1 h of reperfusion, cytosolic, mitochondrial, and microsomal activities were enhanced. Ischemia alone did not change the gel filtration chromatography patterns of PLA2 activity, but ischemia and reperfusion resulted in the appearance of a new peak of activity in cytosolic and mitochondrial fractions (Mr approximately 2-3 kD). Thus, the rat kidney has multiple forms of PLA2 activity, likely representing distinct enzymes, with Ca2+ dependencies suggesting regulation by Ca2+ in vivo. Ischemia and reperfusion result in stable increases of PLA2 activity in each subcellular fraction, perhaps related to covalent modifications of PLA2's, which likely account for membrane phospholipid degradation, and increased tissue levels of unsaturated free fatty acids.