tbuckley/cabot-search huggingface dataset:
TRAIL and Doxorubicin Combination Induces Proapoptotic and Antiangiogenic Effects in Soft Tissue Sarcoma <i>In vivo</i>
Authors: Suizhao Wang, Wenhong Ren, Jeffery Liu, Guy Lahat, Keila Torres, Gonzalo Lopez, Alexander J. Lazar, Andrea Hayes-Jordan, Kebin Liu, Jim Bankson, John D. Hazle, Dina Lev
Journal: Clinical Cancer Research (2010)

Novel therapeutic approaches for complex karyotype soft tissue sarcoma (STS) are crucially needed. Consequently, we assessed the efficacy of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), in combination with chemotherapy, on local and metastatic growth of human STS xenografts in vivo.TRAIL was evaluated alone and combined with low-dose doxorubicin in two human STS severe combined immunodeficient mouse xenograft models using fibrosarcoma (HT1080; wild-type p53) and leiomyosarcoma (SKLMS1; mutated p53), testing for effects on local growth, metastasis, and overall survival. Magnetic resonance imaging was used to evaluate local growth and bioluminescence was used to longitudinally assess lung metastases. Tissues were evaluated through immunohistocemistry and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining for treatment effects on tumor cell proliferation, apoptosis, angiogenesis, angiogenic factors, and TRAIL receptor expression. Quantitative real-time polymerase chain reaction (QRTPCR) angiogenesis array was used to assess therapy-induced gene expression changes.TRAIL/doxorubicin combination induced marked STS local and metastatic growth inhibition in a p53-independent manner. Significantly increased (P < 0.001) host survival was also demonstrable. Combined therapy induced significant apoptosis, decreased tumor cell proliferation, and increased TRAIL receptor (DR4 and DR5) expression in all treated tumors. Moreover, decreased microvessel density was observed, possibly secondary to increased expression of the antiangiogenic factor CXCL10 and decreased proangiogenic interleukin-8 cytokine in response to TRAIL/doxorubicin combination, as was also observed in vitro.Given the urgent need for better systemic approaches to STS, clinical trials evaluating TRAIL in combination with low-dose chemotherapy are potentially warranted.
COPD comorbidities and risk assessment according to GOLD 2011 revision
Authors: Nikolay Kyuchukov, Nikolay Yanev, Zlatina Ivanova, Plamen Pavlov, Pavlina Glogovska, Tsanya Popova, Iliya Krachunov, Yavor Ivanov
Journal: European Respiratory Journal (2013)

Introduction  The GOLD revision 2011 introduced a new approach to COPD classification and treatment.  Aim  Our study examined hospitalized and outpatients with COPD by assessing severity according to the GOLD 2011 document and the comorbidities in the different groups.  Methods  The patients voluntarily filled in specially designed questionnaire. Information about patient medical history, clinical examination, exacerbation history and treatment was gathered. SPSS 16.0 was used for statistical analysis.  Results  Two-hundred and three patients took part in the study. The mean age was 67 years (SD ± 9.5). The patients’ distribution in groups was – 5.4 % in A; 16.7% in B; 3.0% in C; 74.9% in D.  The study found out higher percentage of comorbidities in the high risk groups (C and D) compared to the low risk groups (A and B): concomitant diseases – 83.0% versus 68.2% (p  Conclusion  There is a higher percentage of comorbidities in the high risk groups compared to the low risk groups (p
Phase I Study of Targeted Radioimmunotherapy for Leptomeningeal Cancers Using Intra-Ommaya 131-I-3F8
Authors: Kim Kramer, John L. Humm, Mark M. Souweidane, Pat B. Zanzonico, Ira J. Dunkel, William L. Gerald, Yasmin Khakoo, Samuel D. Yeh, Henry W. Yeung, Ronald D. Finn, Suzanne L. Wolden, Steven M. Larson, Nai-Kong V. Cheung
Journal: Journal of Clinical Oncology (2007)

Tumors metastasizing to the CNS and leptomeninges (LM) are associated with significant mortality. We tested the toxicity, pharmacokinetics, and dosimetry of intraventricular iodine-131-labeled monoclonal antibody 3F8 (131I-3F8) targeting GD2-positive CNS/LM disease in a phase I clinical trial.Adequate CSF flow was determined by pretreatment indium-111-DTPA studies. Fifteen patients received a tracer (1 to 2 mCi) and therapeutic injection (10 to 20 mCi) of intra-Ommaya 131I-3F8. 131I-3F8 pharmacokinetics were studied by serial CSF and blood samplings. Dosimetry was based on pharmacokinetics and region of interest (ROI) analyses on whole-body gamma camera scans. Tumor response was determined by clinical, radiographic, and cytologic criteria.Total absorbed CSF dose was 1.12 to 13.00 Gy by sampling and 1.00 to 13.70 Gy by ROI data. Average dosimetry ratio (Gy/mCi) of the therapy/tracer administration was 0.88 (+/- 0.58) and 1.08 (+/- 0.66) based on CSF pharmacokinetics and ROI analysis, respectively. CSF half-life by sampling was 3 to 12.9 hours. Toxicities included self-limited headache, fever, and vomiting. Dose-limiting toxicity was reached at the 20-mCi dose, when transient elevations in intracranial pressure and chemical meningitis were seen. Three of 13 assessable patients achieved objective radiographic and/or cytologic responses. No late toxicities have been seen in two patients who remain in remission off therapy for more than 3.5 years.Intra-Ommaya 131I-3F8 was generally well tolerated; the maximum-tolerated dose was 10 mCi. A high CSF-to-blood ratio was achieved. Tracer studies reliably predicted the therapeutic dose to the CSF. Radioimmunoconjugates targeting GD2 may have clinical utility in the treatment of CNS/LM malignancies.
Segmental Grafts in Adult and Pediatric Liver Transplantation
Authors: Manuel I. Rodriguez-Davalos, Antonios Arvelakis, Veysel Umman, Vijayakumar Tanjavur, Peter S. Yoo, Sanjay Kulkarni, Stephen M. Luczycki, Michael Schilsky, Sukru Emre
Journal: JAMA Surgery (2013)

The use of technically variant segmental grafts are key in offering transplantation to increase organ availability.To describe the use of segmental allograft in the current era of donor scarcity, minimizing vascular complications using innovative surgical techniques.Retrospective study from August 2007 to August 2012 at a university hospital. A total of 218 consecutive liver transplant patients were reviewed, and 69 patients (31.6%; 38 males and 31 females; mean age, 22.5 years) received segmental grafts from living donors or split/reduced-size grafts from deceased donors.Graft type, vascular and biliary complications, and patient and graft survival.Of 69 segmental transplants, 47 were living donor liver transplants: 13 grafts (27.7%) were right lobes, 22 (46.8%) were left lobes, and 12 (25.5%) were left lateral segments. Twenty-two patients received deceased donor segmental grafts; of these, 11 (50.0%) were extended right lobes, 9 (40.9%) were left lateral segments, 1 (4.5%) was a right lobe, and 1 (4.5%) was a left lobe. Arterial anastomoses were done using 8-0 monofilament sutures in an interrupted fashion for living donor graft recipients and for pediatric patients. Most patients received a prophylactic dose of low-molecular-weight heparin for a week and aspirin indefinitely. There was no incidence of hepatic artery or portal vein thrombosis. Two patients developed hepatic artery stenosis and were treated with balloon angioplasty by radiology. Graft and patient survivals were 96% and 98%, respectively.Use of segmental allografts is essential to offer timely transplantation and decrease waiting list mortality. Living donor liver transplants and segmental grafts from deceased donors are complementary. It is possible to have excellent outcomes combining a multidisciplinary team approach, technical expertise, routine use of anticoagulation, and strict patient and donor selection.
Interleukin-18/Interleukin-18 Binding Protein Signaling Modulates Atherosclerotic Lesion Development and Stability
Authors: Ziad Mallat, Anne Corbaz, Alexandra Scoazec, Pierre Graber, Sami Alouani, Bruno Esposito, Yves Humbert, Yolande Chvatchko, Alain Tedgui
Journal: Circulation Research (2001)

Abstract— Interleukin (IL)-18 is the interferon-γ–inducing factor and has other proinflammatory properties. The precise role of IL-18 in immunoinflammatory diseases remains poorly understood. In this study, we show that in vivo electrotransfer of an expression-plasmid DNA encoding for murine IL-18 binding protein (BP) (the endogenous inhibitor of IL-18) prevents fatty streak development in the thoracic aorta of apoE knockout mice and slows progression of advanced atherosclerotic plaques in the aortic sinus. More importantly, transfection with the IL-18BP plasmid induces profound changes in plaque composition (decrease in macrophage, T cell, cell death, and lipid content and increase in smooth muscle cell and collagen content) leading to a stable plaque phenotype. These results identify for the first time a critical role for IL-18/IL-18BP regulation in atherosclerosis and suggest a potential role for IL-18 inhibitors in reduction of plaque development/progression and promotion of plaque stability. The full text of this article is available at http://www.circresaha.org.
Archaeogenomic Evidence of Punctuated Genome Evolution in Gossypium
Authors: Sarah A Palmer, Alan J Clapham, Pamela Rose, Fábio O Freitas, Bruce D Owen, David Beresford-Jones, Jonathan D Moore, James L Kitchen, Robin G Allaby
Journal: Molecular Biology and Evolution (2012)

Transposable elements (TEs) are drivers of evolution resulting in episodic surges of genetic innovation and genomic reorganization (Oliver KR, Greene WK. 2009. TEs: powerful facilitators of evolution. Bioessays 31:703-714.), but there is little evidence of the timescale in which this process has occurred (Gingerich PD. 2009. Rates of evolution. Ann Rev Ecol Evol Syst. 40:657-675.). The paleontological and archaeological records provide direct evidence for how evolution has proceeded in the past, which can be accessed through ancient DNA to examine genomes using high-throughput sequencing technologies (Palmer SA, Smith O, Allaby RG. 2011. The blossoming of plant archaeogenetics. Ann Anat. 194:146-156.). In this study, we report shotgun sequencing of four archaeological samples of cotton using the GS 454 FLX platform, which enabled reconstruction of the TE composition of these past genomes and species identification. From this, a picture of lineage specific evolutionary patterns emerged, even over the relatively short timescale of a few thousand years. Genomic stability was observed between South American Gossypium barbadense samples separated by over 2,000 miles and 3,000 years. In contrast, the TE composition of ancient Nubian cotton, identified as G. herbaceum, differed dramatically from that of modern G. herbaceum and resembled closely the A genome of the New World tetraploids. Our analysis has directly shown that considerable genomic reorganization has occurred within the history of a domesticated plant species while genomic stability has occurred in closely related species. A pattern of episodes of rapid change and periods of stability is expected of punctuated evolution. This observation is important to understanding the process of evolution under domestication.
Mechanism of the natriuretic effect of unilateral carotid artery traction in the rat.
Authors: S A Mazbar, E Wiedemann, M H Humphreys
Journal: Journal of the American Society of Nephrology (1990)

Unilateral traction on a carotid artery is known to activate the carotid baroreceptor reflex. This maneuver increases sodium excretion in a manner not completely dependent on the renal nerves, suggesting that a humoral factor(s) could be involved. We measured sodium excretion before and after unilateral carotid artery traction or sham traction in anesthetized rats and related the results to the plasma concentration of immunoreactive (IR)-gamma-melanocyte stimulating hormone (gamma-MSH), a peptide known to be natriuretic in other circumstances. In 12 rats undergoing sham traction, sodium excretion did not change and plasma IR-gamma-MSH activity at the end of the experiment was 10.5 +/- 5.4 (SD) fmol/mL. Carotid artery fraction in 20 other rats caused a transient dip in mean arterial pressure of 20.1 +/- 13.2 mm Hg, and sodium excretion increased from 746 +/- 431 to 1,739 +/- 1,436 nEq/min (P less than 0.005). Plasma IR-gamma-MSH was increased to 21.1 +/- 7.1 fmol/mL (P less than 0.001 versus sham). Prior ipsilateral carotid sinus denervation markedly attenuated the carotid artery traction-related dip in blood pressure and prevented both the natriuresis and the increase in IR-gamma-MSH activity seen after this maneuver in intact rats. Pretreatment with anti-gamma-MSH antiserum also blocked the natriuretic response to carotid artery traction, despite a similar transient dip in blood pressure of 18.3 +/- 9.9 mm Hg. These observations suggest that activation of the carotid baroreceptor reflex by unilateral carotid artery traction causes natriuresis that is mediated largely by an increase in the plasma concentration of a peptide or peptides closely related to the gamma-MSH sequence.
Self-induced vomiting and bulimia nervosa: an undetected problem.
Authors: C G Fairburn, P J Cooper
Journal: BMJ (1982)

Six hundred and twenty women who were currently practising self-induced vomiting to control their weight were identified with the help of a women9s magazine. Nineteen women (3.1%) fulfilled diagnostic criteria for anorexia nervosa. Of the remainder, 499 (83.0%) fulfilled diagnostic criteria for bulimia nervosa, a recently described eating disorder. Of these, 56.1% practised self-induced vomiting at least once daily; the mean duration of vomiting was 4.5 years. Most women were of normal body weight. On standardised measures, 68.1% of women showed pronounced psychiatric morbidity and 89% had profoundly disturbed attitudes to food and eating. 56.4% thought they definitely needed medical help, though only 30.1% had ever discussed any aspect of their eating difficulties with a doctor. This study highlights the secrecy that surrounds bulimia nervosa and suggests that it is an important undetected source of psychiatric morbidity.
Carriers of the frequent lipoprotein lipase S447X variant exhibit enhanced postprandial apoprotein B-48 clearance
Authors: Melchior C. Nierman, Jaap Rip, Jan-Albert Kuivenhoven, Daniel H. van Raalte, Barbara A. Hutten, Naohiko Sakai, John J.P. Kastelein, Erik S.G. Stroes
Journal: Metabolism (2005)
Early Pregnancy Insulin Resistance and Subsequent Gestational Diabetes Mellitus
Authors: Karen V. Smirnakis, Abelardo Martinez, Karen Hsu Blatman, Myles Wolf, Jeffrey L. Ecker, Ravi Thadhani
Journal: Diabetes Care (2005)

Gestational diabetes mellitus (GDM), which complicates 3–7% of all pregnancies, is associated with increased maternal and fetal morbidity (1). Identification of early risk markers may result in improved understanding of disease pathogenesis and identification of potential targets for intervention. We sought to determine the association between early pregnancy insulin resistance and subsequent abnormal glucose tolerance in pregnancy.

We conducted two institutional review board–approved, prospective, nested, case-control studies within Massachusetts General Hospital’s Obstetrical Maternal Study (MOMS) comparing subjects with GDM and subjects with abnormal glucose loading test (GLT) results but no GDM with control subjects. Consecutive MOMS participants with singleton gestations between February 2002 and February 2004 who provided fasting blood samples between 16–18 weeks’ gestation, underwent GLT testing at 24–28 weeks’ gestation, and delivered after 34 weeks were eligible. To limit confounding by other etiologies of insulin …
Genetic Pathways to Glioblastoma
Authors: Hiroko Ohgaki, Pierre Dessen, Benjamin Jourde, Sonja Horstmann, Tomofumi Nishikawa, Pier-Luigi Di Patre, Christoph Burkhard, Danielle Schüler, Nicole M. Probst-Hensch, Paulo César Maiorka, Nathalie Baeza, Paola Pisani, Yasuhiro Yonekawa, M. Gazi Yasargil, Urs M. Lütolf, Paul Kleihues
Journal: Cancer Research (2004)

Abstract We conducted a population-based study on glioblastomas in the Canton of Zurich, Switzerland (population, 1.16 million) to determine the frequency of major genetic alterations and their effect on patient survival. Between 1980 and 1994, 715 glioblastomas were diagnosed. The incidence rate per 100,000 population/year, adjusted to the World Standard Population, was 3.32 in males and 2.24 in females. Observed survival rates were 42.4% at 6 months, 17.7% at 1 year, and 3.3% at 2 years. For all of the age groups, younger patients survived significantly longer, ranging from a median of 8.8 months (&amp;lt;50 years) to 1.6 months (&amp;gt;80 years). Loss of heterozygosity (LOH) 10q was the most frequent genetic alteration (69%), followed by EGFR amplification (34%), TP53 mutations (31%), p16INK4a deletion (31%), and PTEN mutations (24%). LOH 10q occurred in association with any of the other genetic alterations and was predictive of shorter survival. Primary (de novo) glioblastomas prevailed (95%), whereas secondary glioblastomas that progressed from low-grade or anaplastic gliomas were rare (5%). Secondary glioblastomas were characterized by frequent LOH 10q (63%) and TP53 mutations (65%). Of the TP53 mutations in secondary glioblastomas, 57% were in hotspot codons 248 and 273, whereas in primary glioblastomas, mutations were more equally distributed. G:C→A:T mutations at CpG sites were more frequent in secondary than primary glioblastomas (56% versus 30%; P = 0.0208). This suggests that the acquisition of TP53 mutations in these glioblastoma subtypes occurs through different mechanisms.
Fatal and Nonfatal Outcomes, Incidence of Hypertension, and Blood Pressure Changes in Relation to Urinary Sodium Excretion
Authors: Katarzyna Stolarz-Skrzypek, Tatiana Kuznetsova, Lutgarde Thijs, Valérie Tikhonoff, Jitka Seidlerová, Tom Richart, Yu Jin, Agnieszka Olszanecka, Sofia Malyutina, Edoardo Casiglia, Jan Filipovský, Kalina Kawecka-Jaszcz, Yuri Nikitin, Jan A Staessen
Journal: JAMA (2011)

Extrapolations from observational studies and short-term intervention trials suggest that population-wide moderation of salt intake might reduce cardiovascular events.To assess whether 24-hour urinary sodium excretion predicts blood pressure (BP) and health outcomes.Prospective population study, involving 3681 participants without cardiovascular disease (CVD) who are members of families that were randomly enrolled in the Flemish Study on Genes, Environment, and Health Outcomes (1985-2004) or in the European Project on Genes in Hypertension (1999-2001). Of 3681 participants without CVD, 2096 were normotensive at baseline and 1499 had BP and sodium excretion measured at baseline and last follow-up (2005-2008).Incidence of mortality and morbidity and association between changes in BP and sodium excretion. Multivariable-adjusted hazard ratios (HRs) express the risk in tertiles of sodium excretion relative to average risk in the whole study population.Among 3681 participants followed up for a median 7.9 years, CVD deaths decreased across increasing tertiles of 24-hour sodium excretion, from 50 deaths in the low (mean, 107 mmol), 24 in the medium (mean, 168 mmol), and 10 in the high excretion group (mean, 260 mmol; P < .001), resulting in respective death rates of 4.1% (95% confidence interval [CI], 3.5%-4.7%), 1.9% (95% CI, 1.5%-2.3%), and 0.8% (95% CI, 0.5%-1.1%). In multivariable-adjusted analyses, this inverse association retained significance (P = .02): the HR in the low tertile was 1.56 (95% CI, 1.02-2.36; P = .04). Baseline sodium excretion predicted neither total mortality (P = .10) nor fatal combined with nonfatal CVD events (P = .55). Among 2096 participants followed up for 6.5 years, the risk of hypertension did not increase across increasing tertiles (P = .93). Incident hypertension was 187 (27.0%; HR, 1.00; 95% CI, 0.87-1.16) in the low, 190 (26.6%; HR, 1.02; 95% CI, 0.89-1.16) in the medium, and 175 (25.4%; HR, 0.98; 95% CI, 0.86-1.12) in the high sodium excretion group. In 1499 participants followed up for 6.1 years, systolic blood pressure increased by 0.37 mm Hg per year (P < .001), whereas sodium excretion did not change (-0.45 mmol per year, P = .15). However, in multivariable-adjusted analyses, a 100-mmol increase in sodium excretion was associated with 1.71 mm Hg increase in systolic blood pressure (P.<001) but no change in diastolic BP.In this population-based cohort, systolic blood pressure, but not diastolic pressure, changes over time aligned with change in sodium excretion, but this association did not translate into a higher risk of hypertension or CVD complications. Lower sodium excretion was associated with higher CVD mortality.
Characterization of Fibroblast-specific Protein 1 in Pulmonary Fibrosis
Authors: William E. Lawson, Vasiliy V. Polosukhin, Ornella Zoia, Georgios T. Stathopoulos, Wei Han, David Plieth, James E. Loyd, Eric G. Neilson, Timothy S. Blackwell
Journal: American Journal of Respiratory and Critical Care Medicine (2004)

Because fibroblasts produce collagen and other extracellular matrix components that are deposited during tissue fibrosis, defining the behavior of these cells is critical to understanding the pathogenesis of fibrotic diseases. We investigated the utility of fibroblast-specific protein 1 (FSP1), a member of the calmodulin S100 troponin C superfamily, for identifying lung fibroblasts in a murine model of pulmonary fibrosis induced by intratracheal administration of bleomycin. Protein and mRNA expression of FSP1 was minimal in untreated lungs, but increased by 1 week after bleomycin administration and remained increased at 2 and 3 weeks after treatment. By immunohistochemistry, the number of FSP1+ cells increased in a dose-dependent manner in the lungs after bleomycin treatment. Colocalization of α1 procollagen and FSP1 in interstitial cells demonstrated that FSP1+ fibroblasts contribute to the deposition of collagen after bleomycin administration. In primary lung cell cultures, lung fibroblasts, but not macrophages or type II alveolar epithelial cells, expressed FSP1. FSP1 also identified fibroblasts in lung biopsy specimens from patients with documented usual interstitial pneumonitis. Therefore, FSP1 is an improved marker for lung fibroblasts that could be useful for investigating the pathogenesis of pulmonary fibrosis.