tbuckley/cabot-search huggingface dataset:
Abstract 193: Adipocytes, obesity and the multiple myeloma microenvironment
Authors: Gervaise H. Henry, Nicholas J. Watson, Rebecca C. O'Neill, Tracy Tabib, Erika M. Bullwinkle, Kathleen L. DeCicco-Skinner
Journal: Cancer Research (2014)

Abstract Multiple myeloma (MM), a hematological malignancy characterized by monoclonal plasma cells in the bone marrow, affects nearly 23,000 Americans per year. Obesity contributes to the development and progression of multiple myeloma, yet the relationship between MM cells and adipocytes found in the tumor microenvironment has not been fully elucidated. To examine how adipocytes contribute to the growth and progression of MM, we co-cultured human myeloma cell lines with primary human adipocytes isolated from lipoaspirates. We found that MM cells directly co-cultured with adipocytes or exposed to their conditioned media had increased viability, angiogenic potential, invasion, colony formation, and production of inflammatory cytokines, when compared to MM cells alone. Moreover, adipocytes from obese individuals (BMI &amp;gt; 30) further compounded this. Thus, we demonstrate an important role for adipocytes in promoting myeloma pathologies. Citation Format: Gervaise H. Henry, Nicholas J. Watson, Rebecca C. O'Neill, Tracy Tabib, Erika M. Bullwinkle, Kathleen L. DeCicco-Skinner. Adipocytes, obesity and the multiple myeloma microenvironment. [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 193. doi:10.1158/1538-7445.AM2014-193
Fish Oil Supplementation and Arrhythmias
Authors: Martin H. Strauss, Paul Dorian, Subodh Verma
Journal: JAMA (2005)

To the Editor: Dr Raitt and colleagues conclude that “fish oil supplementation in patients with ICDs [implantable cardioverter-defibrillators] and recurrent ventricular arrhythmias should be avoided” and that its use “may be proarrhythmic in some patients.” We think that the study findings must be placed into context. Although there was a shortened time to recurrent ventricular tachycardia (VT) with fish oil, there was no increase in mortality or incidence of ventricular fibrillation (VF) nor any effect on defibrillation threshold or the inducibility of VT/VF. The observed increase in the incidence of VT with fish oil use may be limited to a select group of patients in whom the mechanism of VT/VF is secondary to a fixed arrhythmogenic substrate. In contrast, ischemically mediated VT/ VF, by far the most common cause of sudden death in patients with coronary artery disease, appears to be sensitive to the antiarrhythmic properties of fish oil. This is reflected in the American Heart Association’s 2001 Level I recommendation that patients with documented coronary heart disease “consume approximately 1 g of EPA DHA [eicosapentaenoic acid and docosahexaenoic acid] per day, preferably from oily fish.” This recommendation should still apply to the vast majority of patients with coronary artery disease for the prevention of sudden death. Proarrhythmia aside, the study documented an unexpected reduction in hospitalizations for neurological events among patients in the fish oil group (6% vs 0%; P=.04). Although the etiology of these events was not reported, stroke may have been the most common cause. Based on recent data showing that use of omega-3 fatty acids prevented atrial fibrillation after coronary artery bypass surgery, one could speculate that atrial fibrillation, a common cause of stroke, may have been prevented by fish oil consumption. A 12year prospective cohort study demonstrated a significant 31% reduction in new atrial fibrillation in individuals with the highest intake of fatty fish. In patients undergoing coronary artery bypass graft surgery, 2 g/d of fish oil reduced new onset of atrial fibrillation by 54% (P=.013) with a number needed to treat of only 5 patients. Although intriguing, further prospective trials are needed to confirm this finding.
Abstract 13480: Utility of Combined Assessment of Exercise Oscillatory Breathing and Global Circumferential Strain to Predict Cardiac Events in Heart Failure Patients
Authors: Hidekazu Tanaka, Yasunori Tsuboi, Kensuke Matsumoto, Kuniko Dokuni, Yutaka Hatani, Hiroki Matsuzoe, Keiko Hatazawa, Hiromi Toki, HIroyuki Shimoura, Junichi Ooka, Hiroyuki Sano, Takuma Sawa, Yoshiki Motoji, Yasuhide Mochizuki, Kazuhiro Tatsumi, Yoshitada Sakai, Ken-ichi Hirata
Journal: Circulation (2014)

Background: The occurrence of cardiopulmonary exercise testing-derived exercise oscillatory breathing (EOB) is a predictor of survival in heart failure (HF) patients. Whereas, it was recently reported that global circumferential strain (GCS) as assessed by two-dimensional speckle-tracking imaging reflects intrinsic left ventricular (LV) myocardial function and is a powerful predictor of cardiovascular events, and thus appears to be a better predictive parameter than global LV function, including LV ejection fraction (EF). The objectives of our study were to test the hypothesis that a combined assessment of EOB and GCS can further enhance the ability of the method to predict cardiac events in HF patients. Methods: A total of 86 HF patients with LVEF of 44±11% underwent cardiopulmonary exercise testing and echocardiography. GCS was determined as the peak global speckle-tracking strain from mid-LV short-axis view, and GCS of &lt;10.7% was predefined as significant LV myocardial dysfunction for HF patients. EOB definition was based on the criteria as previously reported. Long-term unfavorable outcome events were pre-specified as primary end points of hospitalization for deteriorating HF over 2.0 years. Results: Overall, patients with EOB (n=35) were associates with unfavorable clinical events compared with those without EOB (n=49) (2% vs. 18%, p=0.04). Of 35 patients with EOB, there were 10 patients with EOB and GCS10.7%. The prevalence of unfavorable clinical events of patients with EOB and GCS10.7% (70% vs. 4%, p&lt;0.001). Conclusions: The combined approach of EOB and GCS leads to more accurate prediction of unfavorable cardiac events than using individual parameters in HF patients. The study presented here offers new insights into management of HF patients.
Lesson of the week: Nitrous oxide anaesthesia in the presence of intraocular gas can cause irreversible blindness
Authors: Y F Yang
Journal: BMJ (2002)

Retinal detachment arising from a retinal break occurs in about 1 person per 10 000 per year. 1 Spontaneous retinal reattachment is rare, and retinal reattachment surgery is required to prevent irreversible total loss of vision.Modern vitreoretinal techniques often use intraocular gases as tamponading agents.These gases may persist in the eye for up to three months after surgery.During this period further anaesthesia using nitrous oxide will cause the intraocular gas bubble to expand, 2-5 which can result in sight threatening increases in intraocular pressure.We present a case in which this occurred with devastating consequences.
Immunosuppression and Chagas disease; experience from a non-endemic country
Authors: F. Salvador, A. Sánchez-Montalvá, L. Valerio, N. Serre, S. Roure, B. Treviño, D. Pou, E. Sulleiro, C. Bocanegra, I. Molina
Journal: Clinical Microbiology and Infection (2015)
Caspase inhibition reduces severe pulmonary hypertension in the AdTGF-1β/SU5416 model of angioproliferative pulmonary hypertension and lung fibrosis
Authors: Laszlo Farkas, Daniela Farkas, Donatas Kraskauskas, Jack Gauldie, Martin Kolb, Norbert Voelkel
Journal: European Respiratory Journal (2011)

Pulmonary hypertension (PH) is associated with increased mortality in patients with idiopathic pulmonary fibrosis (IPF). The interaction between the fibrotic process and the pulmonary vasculature is incompletely understood.

The current study aimed to investigate whether broad spectrum caspase inhibition can reduce severe angioproliferative PH in the combined model of AdTGF-β1 lung fibrosis and the VEGF receptor inhibitor SU5416.

Female Sprague Dawley rats received AdTGF-β1 intratracheally at day 0, as well as one dose of SU5416 s.c. or CMC. Some AdTGF-β1/SU5416 animals received the caspase inhibitor Z-Asp-CH2-DCB or vehicle (DMSO) from day 6-28 At day 28, invasive pulmonary hemodynamics were assessed. The right lung was used for protein and RNA isolation, and the left lung was inflated with formalin and processed for histology.

We detected clusters of VWF+ endothelial cells occluding the lumen of small pulmonary arteries in AdTGF-β1/SU5416, together with severe PH in AdTGF-β1/SU5416 rats vs. AdTGF-β1/CMC. At the same time, lung fibrosis was increased, as indicated by elevated mRNA expression of profibrotic and matrix genes. Western blots showed a significant increase in caspase-3 cleavage in AdTGF-β1/SU5416 rats. Treatment with Z-Asp-CH2-DCB reduced right ventricular systolic pressures by 19.4 mmHg in average in AdTGF-β1/SU5416 animals (P<0.05 vs. DMSO).

In conclusion, our results indicate that angioproliferative pulmonary vasculopathy was induced in this new model, together with severe fibrosis, and that increased apoptosis contributes to both increased fibrosis and vascular pathology.
Abstract 5541: Proteasome inhibitor synergizes with histone deacetylase inhibitor to trigger ROS- and ER stress-induced apoptosis of nasopharyngeal carcinoma independent of aggresome disruption
Authors: Alan K. Chiang, Kwai Fung Hui
Journal: Cancer Research (2014)

Abstract Proteasome inhibitor and histone deacetylase inhibitor (HDACi) can synergistically induce apoptosis of cancer cells through aggresome disruption or induction of endoplasmic reticulum (ER) stress. We previously reported that suberoylanilide hydroxamic acid (SAHA), a pan-HDACi, and bortezomib, a proteasome inhibitor can synergistically induce apoptosis of nasopharyngeal carcinoma (NPC) cells through reactive oxygen species (ROS)-driven caspase-dependent mechanism. Here, we wish to investigate the role of aggresome disruption or ER stress in the process. We first tested the effect of bortezomib combining with a more specific HDACi, including MS-275, apicidin or romidepsin, on proliferation of NPC cells. Bortezomib could synergize with each of the specific HDACis to induce killing of the NPC cells. Strong apoptosis was demonstrated by the proteolytic cleavage of PARP and caspase-3, -8 and -9 as well as the high percentage of annexin V/propidium iodide (AV/PI)-positive NPC cells upon treatment with combination of bortezomib at 7.5 to 15 nM and romidepsin at 2.5 to 5 nM. Consistently, the apoptosis was ROS- and caspase-dependent. Interestingly, α-tubulin, a key substrate of histone deacetylase 6, was not acetylated, arguing against the involvement of aggresome disruption. In contrast, ER stress induction might be involved because ATF-4 and CHOP, which are markers of ER stress, were up-regulated by combined bortezomib/romidepsin and inhibition of caspase-4 could suppress the apoptosis. Furthermore, addition of ROS scavenger, N-acetyl-cysteine, suppressed the expression of ATF-4 and CHOP. We conclude that proteasome inhibitor can synergize with HDACi to trigger ROS- and ER stress-induced apoptosis of NPC cells, independent of aggresome disruption. This project is funded by NPC Area of Excellence (AoE/M 06/08 Center for Nasopharyngeal Carcinoma Research), CRCG (#10401264) and Epstein-Barr virus research (# 20004525) grants of A.K.S. Chiang. Citation Format: Alan K. Chiang, Kwai Fung Hui. Proteasome inhibitor synergizes with histone deacetylase inhibitor to trigger ROS- and ER stress-induced apoptosis of nasopharyngeal carcinoma independent of aggresome disruption. [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 5541. doi:10.1158/1538-7445.AM2014-5541
Liver transplantation in HBs antigen (HBsAg) carriers
Authors: Rainer Müller, Gundolf Gubernatis, Margarete Farle, Gabriele Niehoff, Heide Klein, Christian Wittekind, Günter Tusch, Hans-Ulrich Lautz, Klaus Böker, Walter Stangel, Rudolf Pichlmayr
Journal: Journal of Hepatology (1991)
The private finance initiative: Planning the "new" NHS: downsizing for the 21st century
Authors: A. M Pollock, M. G Dunnigan, D. Gaffney, D. Price, J. Shaoul
Journal: BMJ (1999)

This is the third of four articles on Britain's public-private partnership in health care

Growing numbers of health authorities and NHS trusts are carrying out service “reconfigurations” which involve the centralisation of services from two or more sites and the sale or downgrading of the other sites Where structural change requires major investment, the private finance initiative is the only method of financing it. However, the higher cost of the private finance initiative increases the cost pressures on the revenue budgets.1 The result is service contraction: on average, bed numbers are to be reduced by 31% over the next three to five years (table 1). It should be noted that, at a national level, there has been no reduction in acute beds since 1994-5 (figure).2

View this table:

Table 1. 
Changes in bed numbers at NHS trusts under private finance initiative development. Values are average numbers of beds available daily (all specialties)



The relationship between new investment and service configuration raises questions about the planning process: who is making decisions on future services, and on what basis?3 When faced with questions about the relative importance of clinical and financial factors in service planning, the government has tended to argue that the crucial decisions are all made by clinicians Clinical directors are responsible for agreeing and medical directors for approving full business cases; however, healthcare planning has never been a core clinical competence, and making decisions is very different from agreeing to decisions taken by others This issue was raised earlier this year in correspondence in the Glasgow Herald , in which the Scottish health minister responded to criticism of bed numbers at the controversial Royal Infirmary of Edinburgh private finance initiative scheme by stating, “It is the clinicians who decide on the number of beds…. The assumptions on bed numbers were developed …
Long-Term Culture of Human CD34+ Progenitors With FLT3-Ligand, Thrombopoietin, and Stem Cell Factor Induces Extensive Amplification of a CD34−CD14− and a CD34−CD14+ Dendritic Cell Precursor
Authors: Jean-François Arrighi, Conrad Hauser, Bernard Chapuis, Rudolf H. Zubler, Vincent Kindler
Journal: Blood (1999)
Kurzes Lehrbuch der Kinderkrankheiten.
Authors: Heinrich Lehndorff
Journal: JAMA (1923)

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Abstract 3495: A nucleolus-predominant piggyBac transposase increases transposition efficiency in human cancer cells
Authors: Jin-Bon Hong, Fu-Ju Chou, Amy T. Ku, Hsiang-Hsuan Fan, Tung-Lung Lee, Yung-Hsin Huang, I-Chang Su, You-Tzung Chen
Journal: Cancer Research (2014)

Abstract PiggyBac is a prevalent transposon system used to deliver transgenes into and to functionally explore the mammalian untouched genomic territory. Efforts to increase its transposition efficiency in mammals through engineering the corresponding transposase (PBase) codon usage to improve its expression level is reported. The hyperactive PBase developed through screening for mutant variants are also established. To increase the safety for its potential use in regenerative medicine applications, site-specific transposition using engineered Zn finger-, Gal4- fused PBase, and an excision-prone PBase variant are also successfully developed. Here we report the construction of a nucleolus predominant PBase, NP-mPB, by adding a nucleolus predominant (NP) signal peptide from HIV-1 TAT protein to a mammalian codon optimized PBase (mPB). Although there is a predominant fraction of the NP-mPB-tGFP fusion proteins concentrated in the nucleoli, an insertion site preference toward nuleolar organizer regions (NORs) is not detected. Instead a 3-fold increase in piggyBac transposition efficiency is found in human cancer cell line. Citation Format: Jin-Bon Hong, Fu-Ju Chou, Amy T. Ku, Hsiang-Hsuan Fan, Tung-Lung Lee, Yung-Hsin Huang, I-Chang Su, You-Tzung Chen. A nucleolus-predominant piggyBac transposase increases transposition efficiency in human cancer cells. [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 3495. doi:10.1158/1538-7445.AM2014-3495
A phase II study of ARQ 501 in patients with advanced squamous cell carcinoma of the head and neck
Authors: A. Kawecki, D. R. Adkins, C. C. Cunningham, E. Vokes, D. M. Yagovane, G. Dombal, P. Koralewski, Y. Hotko, V. Vladimirov
Journal: Journal of Clinical Oncology (2007)

16509 Background: ARQ 501 is a DNA damage checkpoint pathway activator whose effect is to induce selective cell death in cancer cells, independent of the tumor cell's p53 status. Current evidence implicates a rapid and sustained increase of the pro-apoptotic protein E2F-1 by ARQ 501 as the mechanism of action. Cancer cells are selectively affected due to their pre-existing DNA damage. In initial clinical trials, there was evidence of activity in some patients with head and neck cancer and pre-clinical investigations also supported this application. Therefore, a phase 2 trial is warranted in this patient population. Methods: A phase 2 study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck who had received up to 3 prior systemic therapies was initiated to assess overall response rate, progression free survival at six months, and to further characterize safety. Cycles consist of four weekly administrations of ARQ 501 at a dose of 450 mg/m 2 . Dose escalation is allowed if a patient successfully completed a full cycle of therapy and had no related grade 2 adverse events. Results: 59 patients have been enrolled to date and 47 have received at least one infusion of ARQ 501. Data is available for 34 patients (27M / 7F, median age, 57 years). Of the 47 patients treated, 11 patients did not reach a post baseline assessment (2 deaths, 8 PD prior to week 8 and 1 withdrew consent). Although at the current date, most patients have not reached their first tumor evaluation, 5 have been assessed for response per RECIST at eight weeks and one patient is demonstrating stable disease. The drug has been well tolerated with the most common adverse event being anemia (11% ) with corresponding edema, fatigue (both 5%), dyspnea (4%), and hyperbilirubinemia (2%). Conclusions: ARQ 501 is well tolerated in patients with advanced, recurrent or persistent squamous cell carcinoma of the head and neck. Enrollment is ongoing and further results will be presented. No significant financial relationships to disclose.
836. Transendothelial Transport Studies of Polymer-Based Gene Delivery Systems
Authors: Eric Mennesson, Pierre Sandrin, Claudine Kieda, Patrick Erbacher, Patrick Midoux, Chantal Pichon
Journal: Molecular Therapy (2004)

These last decade, efforts have been made to design polymer-based gene delivery systems that incorporate viral-like features for powerful transfection. Efficient systemic administration of these systems will be achieved when DNA-polymer complexes (polyplexes) can get over endothelium barrier to reach the underlying target cells. The respiratory tract is lined by epithelial cells with underlying endothelial-lined cappillaries, forming an integrated system and acting as a barrier. The goal of this work is to investigate the transendothelial passage of polyplexes made either with histidylated polylysine (His-pLK) or polyethyleneimine (PEI) by using a cell culture model reflecting this integrated system. We have optimized culture conditions to get highly polarized monolayers of a human lung microvascular endothelial cell line (HLMEC) and of a CF human airway epithelial cell line (CFTE29o-). A monolayer of HLMEC or a bilayer model, confluent epithelial and endothelial cell layers growing on opposite sides of PET filter inserts were used for this study.
Cellular and bacterial profiles associated with oral epitheliumâmicrobiota interactions
Authors: Jeffrey J. Mans, Erik L. Hendrickson, Murray Hackett, Richard J. Lamont
Journal: Periodontology 2000 (2009)

In the last several years, the momentum towards utilizing global profiling methods has increased, and many studies have incorporated these approaches in order to gain insights into previously undetected host or microbe responses during the host-microbe encounter.Over 100 studies available on NIH Pubmed have used microarrays or similar technologies to assess the transcriptional basis for observed physiological outcomes.Further, these studies have revealed a high level of transcriptional activity that is not readily observable and, indeed, often phenotypically silent; presumably the cell's attempt to maintain homeostasis and symbiotic harmony (12, 28).Additionally, proteomic studies which profile the entire arsenal of proteins present in a cell at a given time are now also possible.Each technique has its own advantages and limitations, and the technologies themselves are reviewed elsewhere (3,10,16,19,20,30,34).As also reviewed previously, the epithelium is the first line of defense to human infections initiating at mucosal membranes (4, 7), and several studies have demonstrated the specific and active nature of the epithelial response to microbial encounters.The response of the epithelium to bacterial, viral, fungal and protozoal challenge has yielded significant insights into the role of the epithelium in host defense.In addition to a passive role as a physical barrier, the epithelium actively participates in the recruitment of immune effectors, and can directly fend off microbes via defensins and other innate immune mechanisms.