tbuckley/cabot-search huggingface dataset:
INFLAMMATION AND ATHEROSCLEROSIS
Authors: Göran K. Hansson, Anna-Karin L. Robertson, Cecilia Söderberg-Nauclér
Journal: Annual Review of Pathology Mechanisms of Disease (2006)

Atherosclerosis, the cause of myocardial infarction, stroke, and ischemic gangrene, is an inflammatory disease. The atherosclerotic process is initiated when cholesterol-containing low-density lipoproteins accumulate in the intima and activate the endothelium. Leukocyte adhesion molecules and chemokines promote recruitment of monocytes and T cells. Monocytes differentiate into macrophages and upregulate pattern recognition receptors, including scavenger receptors and toll-like receptors. Scavenger receptors mediate lipoprotein internalization, which leads to foam-cell formation. Toll-like receptors transmit activating signals that lead to the release of cytokines, proteases, and vasoactive molecules. T cells in lesions recognize local antigens and mount T helper-1 responses with secretion of pro-inflammatory cytokines that contribute to local inflammation and growth of the plaque. Intensified inflammatory activation may lead to local proteolysis, plaque rupture, and thrombus formation, which causes ischemia and infarction. Inflammatory markers are already used to monitor the disease process and anti-inflammatory therapy may be useful to control disease activity.
Effectiveness of corticosteroid injections versus physiotherapy for treatment of painful stiff shoulder in primary care: randomised trial
Authors: D A W M van der Windt, B W Koes, W Deville, A J P Boeke, B A de Jong, L M Bouter
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective</b> : To compare the effectiveness of corticosteroid injections with physiotherapy for the treatment of painful stiff shoulder. <b>Design</b> : Randomised trial. <b>Setting</b> : 40 general practices. <b>Subjects</b> : 109 patients consulting general practitioners for shoulder pain were enrolled in the trial. <b>Interventions</b> : Patients were randomly allocated to 6 weeks of treatment either with corticosteroid injections (53) or physiotherapy (56). <b>Main outcome measures</b> : Outcome assessments were carried out 3, 7, 13, 26, and 52 weeks after randomisation; some of the assessments were done by an observer blind to treatment allocation. Primary outcome measures were the success of treatment as measured by scores on scales measuring improvement in the main complaint and pain, and improvement in scores on a scale measuring shoulder disability. <b>Results</b> : At 7 weeks 40 (77%) out of 52 patients treated with injections were considered to be treatment successes compared with 26 (46%) out of 56 treated with physiotherapy (difference between groups 31%, 95% confidence interval 14% to 48%). The difference in improvement favoured those treated with corticosteroids in nearly all outcome measures; these differences were statistically significant. At 26 and 52 weeks differences between the groups were comparatively small. Adverse reactions were generally mild. However, among women receiving treatment with corticosteroids adverse reactions were more troublesome: facial flushing was reported by 9 women and irregular menstrual bleeding by 6, 2 of whom were postmenopausal. <b>Conclusions</b> : The beneficial effects of corticosteroid injections administered by general practitioners for treatment of painful stiff shoulder are superior to those of physiotherapy. The differences between the intervention groups were mainly the result of the comparatively faster relief of symptoms that occurred in patients treated with injections. Adverse reactions were generally mild but doctors should be aware of the potential side effects of injections of triamcinolone, particularly in women.
Metformin in Chemotherapy-naive Castration-resistant Prostate Cancer: A Multicenter Phase 2 Trial (SAKK 08/09)
Authors: Christian Rothermundt, Stefanie Hayoz, Arnoud J. Templeton, Ralph Winterhalder, Räto T. Strebel, Daniela Bärtschi, Michael Pollak, Lillianne Lui, Kathrin Endt, Ralph Schiess, Jan H. Rüschoff, Richard Cathomas, Silke Gillessen
Journal: European Urology (2014)
Abstract B41: Investigating ARID3B regulation of ovarian cancer metastasis
Authors: Katrina Gellerman, Serene Samyesudhas, Stancy Joseph, Karen Cowden Dahl
Journal: Cancer Research (2013)

Abstract Over 60% of ovarian cancer cases are detected with widespread metastases. In an effort to define the associated molecular mechanisms of metastasis in ovarian cancer, recent findings have implicated a novel DNA-binding protein, ARID3B, as a contributor to ovarian cancer growth and metastasis. We recently demonstrated that increased expression of ARID3B promotes metastatic growth of ovarian cancer cells in a xenograft mouse model. The purpose of this study is to identify target genes of ARID3B, with the goal of elucidating a mechanism for this metastatic support. ChIP-on-chip analysis comparing ovarian cancer cells in the presence and absence of exogenous overexpression of ARID3B revealed a multitude of potential gene targets. These targets have been functionally sorted into 21 distinct groups and among these groups, 21 genes were selected for further analysis. Validation of these targets via RT-PCR has identified c-Myc, a known regulator of metastasis, as a putative target of ARID3B. Our results reveal an increase in c-Myc mRNA levels in response to ARID3B, implicating c-Myc as putative direct target of ARID3B. We used chromatin immunoprecipitation to study the potential interaction of ARID3B with the c-Myc promoter. The specifics of the regulation of c-Myc are currently under investigation. In conjunction with gene regulation, metastasis-associated phenotypes were examined, as well. ARID3B overexpression increases extracellular matrix adhesion and vitronectin haptotaxis. Specifically, we investigated the contribution c-Myc to ARID3B induced adhesion and motility as a means for promoting metastatic progression. We accomplished this via adhesion and haptotaxis assays using ovarian cancer cells exogenously overexpressing ARID3B, followed by siRNA knockdown of c-Myc. Further study will serve to define how ARID3B regulation of c-Myc contributes to ovarian cancer progression. Should c-Myc prove to be a biologically relevant target, ARID3B regulation of c-Myc could represent an important mechanism for the associated advancement of ovarian cancer metastasis. Citation Format: Katrina Gellerman, Serene Samyesudhas, Stancy Joseph, Karen Cowden Dahl. Investigating ARID3B regulation of ovarian cancer metastasis. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Invasion and Metastasis; Jan 20-23, 2013; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2013;73(3 Suppl):Abstract nr B41.
Phase I Trial of Bevacizumab Plus Escalated Doses of Sunitinib in Patients With Metastatic Renal Cell Carcinoma
Authors: Darren R. Feldman, Michael S. Baum, Michelle S. Ginsberg, Hani Hassoun, Carlos D. Flombaum, Susanne Velasco, Patricia Fischer, Ellen Ronnen, Nicole Ishill, Sujata Patil, Robert J. Motzer
Journal: Journal of Clinical Oncology (2009)

Purpose Both bevacizumab and sunitinib target the vascular endothelial growth factor pathway and demonstrate activity against advanced renal cell carcinoma (RCC). In this phase I study, the maximum-tolerated dose (MTD) and safety of sunitinib in combination with bevacizumab were examined in patients with advanced RCC. Patients and Methods Three cohorts of three to six patients were treated with escalated doses of daily oral sunitinib (ie, 25 mg, 37.5 mg, 50 mg) for 4 weeks followed by a 2-week break and with fixed doses of bevacizumab (10 mg/kg) intravenously once every 2 weeks. Dose-limiting toxicities (DLTs) were assessed during the first cycle to determine the MTD, and an expanded cohort was treated to obtain additional safety information. Results Of 26 study participants, 25 received treatment at one of three dose levels. Grade 4 hemorrhage, identified as a DLT, occurred in one patient in each of cohorts 2 and 3. The MTD was determined to be sunitinib 50 mg/bevacizumab 10 mg/kg, but chronic therapy at this dose level frequently resulted in grades 3 to 4 hypertension and hematologic and vascular toxicities. Overall, 48% of patients discontinued treatment because of adverse events. One complete and 12 partial responses were observed, which provided an objective response rate of 52%. Conclusion In this phase I trial of patients with metastatic RCC, the combination of sunitinib and bevacizumab caused a high degree of hypertension and vascular and hematologic toxicities at the highest dose level. We do not plan to pursue additional study of this regimen at these doses in patients with RCC.
Secular trends in birth weight, BMI, and diabetes in the offspring of diabetic mothers.
Authors: R S Lindsay, R L Hanson, P H Bennett, W C Knowler
Journal: Diabetes Care (2000)

OBJECTIVE: The offspring of mothers who had diabetes during pregnancy experience increased risk later of diabetes and obesity later. We hypothesized that, in light of the historical improvements in the management of diabetes during pregnancy, these late consequences of the early environment might be diminishing with time. RESEARCH DESIGN AND METHODS: Birth weight and information on BMI and glucose tolerance have been collected as part of the epidemiological survey of the Gila River Indian Community in Arizona. We examined birth weight, BMI, and diabetes in offspring of mothers with type 2 diabetes during pregnancy born in four 10-year time intervals since 1955 compared with offspring whose mothers either had not developed diabetes or were prediabetic (i.e., developed diabetes after the index pregnancy). RESULTS: Offspring of diabetic mothers (ODM) were heavier at birth, had a higher BMI at all ages throughout childhood, and had an increased incidence rate of diabetes in childhood and early adulthood (7- to 20-fold, offspring of nondiabetic mothers [ONDM]; 3- to 5-fold, offspring of prediabetic mothers [OPDM]). Relative differences in birth weight and BMI between ODM and ONDM were greatest for those born before 1965. In those born after 1965, despite secular trends to higher BMI and diabetes incidence in the ONDM, differences in BMI and birth weight of ODM versus ONDM and OPDM appeared to have been maintained. CONCLUSIONS: With the possible exception of individuals born before 1965, the increased risk of diabetes and obesity experienced by ODM does not seem to be diminishing with time.
The potential impact of anaemia of chronic disease in COPD
Authors: T. Similowski, A. Agustí, W. MacNee, B. Schönhofer
Journal: European Respiratory Journal (2006)

Anaemia of chronic disease (ACD), with chronically low levels of circulating haemoglobin, is an immune driven abnormality that occurs in many inflammatory diseases, and also in chronic heart failure. Although chronic obstructive pulmonary disease (COPD) is “traditionally” associated with polycythaemia, the systemic inflammation that is now recognised as a feature of COPD makes it a possible cause of ACD. If present in COPD, anaemia could worsen dyspnoea and limit exercise tolerance. Preliminary evidence suggests that anaemia in COPD patients may be more prevalent than expected, concerning 10–15% of patients suffering from severe forms of the disease. A database study conducted in 2,524 COPD patients being prescribed long-term oxygen therapy has shown that a low haematocrit is a strong predictor of survival in this population, before body mass index, and is associated with more hospitalisations and a longer cumulative duration of hospitalisation. COPD patients with low haemoglobin levels have a poorer prognosis than COPD patients with normal haemoglobin levels in the event of acute gastrointestinal bleeding or after elective aneurysm repair. Raising haemoglobinaemia through transfusion decreases minute ventilation and work of breathing in COPD patients. These preliminary evidences point to the need to study the prevalence of anaemia, and its physiological and clinical impact in chronic obstructive pulmonary disease. When this body of knowledge is available, the question of the putative benefits of raising haemoglobinaemia in chronic obstructive pulmonary disease will have to be addressed.
Src Inhibits Adriamycin-Induced Senescence and G2 Checkpoint Arrest by Blocking the Induction of p21waf1
Authors: Arnaud Vigneron, Igor B. Roninson, Erick Gamelin, Olivier Coqueret
Journal: Cancer Research (2005)

Abstract DNA-damaging drugs stop tumor cell proliferation by inducing apoptosis, necrosis, or senescence. Cyclin-dependent kinase inhibitor p21waf1 is an important regulator of these responses, promoting senescence and preventing aberrant mitosis that leads to cell death. Because tumors expressing oncogenic tyrosine kinases are relatively resistant to DNA-damaging agents, the effects of Src on cellular responses to anticancer drug Adriamycin were investigated. Src expression increased drug survival in HT1080 fibrosarcoma cells, as measured by the colony formation assay, and strongly inhibited Adriamycin-induced senescence. Src also decreased the number of apoptotic cells while increasing the fraction of cells dying through necrosis. In addition, Src inhibited the G2 and G1 tetraploidy checkpoints of Adriamycin-treated cells, permitting these cells to proceed into mitosis and subsequently double their DNA content. Inhibition of senescence and G2-G1 checkpoints in Src-expressing cells was associated with the failure of these cells to up-regulate p21waf1 in response to Adriamycin. The failure of p21waf1 induction, despite increased expression of p53 and its binding to p21waf1 promoter, was mediated by the up-regulation of c-Myc, a negative regulator of p21waf1 transcription. Conversely, ectopic expression of p21waf1 inhibited Myc transcription in Src-expressing cells, an effect that was associated with the interaction of p21waf1 with the STAT3 transcription factor at the Myc promoter. These results reveal a complex effect of Src on cellular drug responses and provide an explanation for the effect of this oncogene on cellular drug resistance.
Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study
Authors: L. de Leval, C. Bonnet, C. Copie-Bergman, L. Seidel, M. Baia, J. Brière, T.J. Molina, B. Fabiani, T. Petrella, J. Bosq, C. Gisselbrecht, R. Siebert, H. Tilly, C. Haioun, G. Fillet, P. Gaulard
Journal: Annals of Oncology (2012)
Decreased Nitric Oxide Synthesis in Human Endothelial Cells Cultured on Type I Collagen
Authors: L. González-Santiago, S. López-Ongil, M. Rodríguez-Puyol, D. Rodríguez-Puyol
Journal: Circulation Research (2002)

Endothelial dysfunction, considered as a defective vascular dilatation after certain stimuli, is characteristic of different pathological conditions, such as hypertension, atherosclerosis, or diabetes. A decreased synthesis or an increased degradation of nitric oxide (NO) has been postulated as the mechanism responsible for this alteration. The present experiments were designed to test the hypothesis that the presence of an abnormal extracellular matrix in vessel walls could be responsible for the decreased NO synthesis observed in these pathological conditions. Experiments were performed in cultured human umbilical vein endothelial cells (HUVECs) grown on type IV (Col. IV) or type I (Col. I) collagen. Cells seeded on Col. I showed decreased nitrite synthesis, nitric oxide synthase activity, eNOS protein content, and eNOS mRNA expression when compared with cells grown on Col. IV. Moreover, cells grown on Col. I failed to respond to glucose oxidase activation of the eNOS system. In both cases, the changes in the eNOS mRNA expression seemed to depend on the modulation of eNOS promoter activity. The downregulation of eNOS induced by Col. I was blocked by D6Y, a peptide that interferes with the Col. I-dependent signals through integrins, as well as by specific anti-integrin antibodies. Moreover, a decreased activation of integrin-linked kinase (ILK) may explain the effects observed in Col. I-cultured cells because the activity of this kinase was decreased in these cells and ILK modulation prevented the Col. I-induced changes in HUVECs. Taken together, these findings may contribute to explaining the basis of endothelial dysfunction in some vascular diseases.
Rupture of Aortic Aneurysm Into Inferior Vena Cava
Authors: Morton Glasser
Journal: JAMA (1967)

<h3>To the Editor:—</h3> Rupture of an abdominal aortic aneurysm into the inferior vena cava is a rare occurrence usually accompanied by dramatic symptoms. Of 11 patients described by Beall et al,<sup>1</sup>all except two had pain in the abdomen, back, or lower extremities; eight had swelling of the lower extremities; nine had a pulsating abdominal mass; ten had an abdominal murmur; and only four had cardiac decompensation. The intriguing aspects of the case presented here are the few symptoms, the conspicuous absence of pain, and the scarcity of physical findings during the early stages of the disease. <h3>Report of a Case:—</h3> A 60-year-old man was admitted to the hospital at 10:30 PM on Jan 24, 1967, because of nausea and vomiting, headache, and numbness or cramps in the legs for the past few days. He also complained of insomnia and restlessness. The history was noncontributory. Review of systems revealed
Interlaboratory Evaluation of Rodent Pulmonary Responses to Engineered Nanomaterials: The NIEHS Nano GO Consortium
Authors: James C. Bonner, Rona M. Silva, Alexia J. Taylor, Jared M. Brown, Susana C. Hilderbrand, Vincent Castranova, Dale Porter, Alison Elder, Günter Oberdörster, Jack R. Harkema, Lori A. Bramble, Terrance J. Kavanagh, Dianne Botta, Andre Nel, Kent E. Pinkerton
Journal: Environmental Health Perspectives (2013)

Background: Engineered nanomaterials (ENMs) have potential benefits, but they also present safety concerns for human health. Interlaboratory studies in rodents using standardized protocols are needed to assess ENM toxicity.Methods: Four laboratories evaluated lung responses in C57BL/6 mice to ENMs delivered by oropharyngeal aspiration (OPA), and three labs evaluated Sprague-Dawley (SD) or Fisher 344 (F344) rats following intratracheal instillation (IT). ENMs tested included three forms of titanium dioxide (TiO2) [anatase/rutile spheres (TiO2-P25), anatase spheres (TiO2-A), and anatase nanobelts (TiO2-NBs)] and three forms of multiwalled carbon nanotubes (MWCNTs) [original (O), purified (P), and carboxylic acid "functionalized" (F)]. One day after treatment, bronchoalveolar lavage fluid was collected to determine differential cell counts, lactate dehydrogenase (LDH), and protein. Lungs were fixed for histopathology. Responses were also examined at 7 days (TiO2 forms) and 21 days (MWCNTs) after treatment.Results: TiO2-A, TiO2-P25, and TiO2-NB caused significant neutrophilia in mice at 1 day in three of four labs. TiO2-NB caused neutrophilia in rats at 1 day in two of three labs, and TiO2-P25 and TiO2-A had no significant effect in any of the labs. Inflammation induced by TiO2 in mice and rats resolved by day 7. All MWCNT types caused neutrophilia at 1 day in three of four mouse labs and in all rat labs. Three of four labs observed similar histopathology to O-MWCNTs and TiO2-NBs in mice.Conclusions: ENMs produced similar patterns of neutrophilia and pathology in rats and mice. Although interlaboratory variability was found in the degree of neutrophilia caused by the three types of TiO2 nanoparticles, similar findings of relative potency for the three types of MWCNTs were found across all laboratories, thus providing greater confidence in these interlaboratory comparisons.
Local Gene Transduction of Cyclooxygenase-1 Increases Blood Flow in Injured Atherosclerotic Rabbit Arteries
Authors: Qi Liu, Zhi-Qiang Chen, George C. Bobustuc, Janice M. McNatt, Harry Segall, Su Pan, James T. Willerson, Pierre Zoldhelyi
Journal: Circulation (2005)

Background— Cyclooxygenase-1 (COX-1) is the rate-limiting component in the synthesis of prostacyclin (PGI 2 ), an important vasodilator and antithrombotic molecule. In balloon-injured, atherosclerosis-free porcine arteries, COX-1 gene transduction increases PGI 2 production, induces durable vasodilation, and reduces thrombus formation. We tested the effectiveness of COX-1 local gene transduction for the prevention of postangioplasty restenosis in atherosclerotic arteries in a hypercholesterolemic rabbit model. Methods and Results— We injured 1 carotid artery in 43 Watanabe heritable hyperlipidemic rabbits and performed local gene transduction using a viral vector containing the COX-1 gene (AdCOX-1, n=22) or no genes (Adnull, n=21). Three days later, AdCOX-1–treated arteries stimulated with arachidonic acid produced 100% more PGI 2 ( P &lt;0.01), 400% more prostaglandin E 2 (PGE 2 ) ( P &lt;0.01), 400% more prostaglandin E 1 (PGE 1 ) ( P &lt;0.01), and 250% more cAMP ( P &lt;0.05) than Adnull-treated arteries. Twenty-eight days after treatment, Doppler sonography showed that blood flow velocity was preserved in AdCOX-1–treated arteries (ratio 0.92, injured compared with contralateral uninjured carotid artery) but reduced in Adnull-treated arteries (ratio 0.39), suggesting that AdCOX-1 prevented restenosis after injury. COX-1–transduced arteries also showed 80% greater lumen area 28 days after injury ( P &lt;0.01). Conclusions— The effectiveness of COX-1 in preventing restenosis and preserving normal blood flow 28 days after injury results from increased lumen area caused by durable vasodilation. COX-1 efficacy correlates with an early increase in the production of PGI 2 , PGE 2 , PGE 1 (known to cause vasodilation), and cAMP. These results demonstrate for the first time that COX-1 gene transduction is an effective treatment for the prevention of postangioplasty restenosis of atherosclerotic arteries under clinically relevant conditions.
Toward Primary Prevention of Asthma. Reviewing the Evidence for Early-Life Respiratory Viral Infections as Modifiable Risk Factors to Prevent Childhood Asthma
Authors: Amy S. Feldman, Yuan He, Martin L. Moore, Marc B. Hershenson, Tina V. Hartert
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

A first step in primary disease prevention is identifying common, modifiable risk factors that contribute to a significant proportion of disease development. Infant respiratory viral infection and childhood asthma are the most common acute and chronic diseases of childhood, respectively. Common clinical features and links between these diseases have long been recognized, with early-life respiratory syncytial virus (RSV) and rhinovirus (RV) lower respiratory tract infections (LRTIs) being strongly associated with increased asthma risk. However, there has long been debate over the role of these respiratory viruses in asthma inception. In this article, we systematically review the evidence linking early-life RSV and RV LRTIs with asthma inception and whether they could therefore be targets for primary prevention efforts.