tbuckley/cabot-search huggingface dataset:
Abstract 17362: Regulation of Oxidative Stress and Apoptotic Signaling in Cardiac Myocytes by G Protein-Coupled Receptor Kinase-2: The Role of NADPH Oxidases
Authors: Ricky Malhotra, Tiju Theccanat, Shahab A Akhter
Journal: Circulation (2011)

Oxidative stress due to generation of reactive oxygen species (ROS) is an important mechanism of cardiac myocyte death following ischemia-reperfusion (I-R) injury and can lead to heart failure. NADPH oxidases (Nox) are major cellular enzymatic sources for superoxide (O 2 ) radical production and Nox2 and Nox4 are the two predominant isoforms expressed in the heart. The mechanisms by which these Nox isoforms are regulated in the heart after various stresses are unclear. G protein-coupled receptor kinase-2 (GRK2) is a critical regulator of β-adrenergic signaling and cardiac function. We hypothesized that GRK2 may play a role in regulating cardiac myocyte oxidative stress and apoptosis. Cardiac myocytes were exposed to 3 hours of hypoxia (2% O 2 , 5% CO 2 , 93% N 2 ) followed by 3 hours of reoxygenation (5% CO 2 , 95% air). Hypoxia-reoxygenation (H-R) led to significant 3.5-fold upregulation of GRK2 activity as well as ROS production (4.7±0.7 vs 1.1±0.4 nmoles/min/mg protein) and apoptosis measured by caspase-3 activity (6.2±1.5 vs 1.8±0.6 fluorimetric units/mg protein) compared to normoxic controls. Interestingly, 4-fold overexpression of GRK2 by adenoviral infection led to an identical 3-fold increase in ROS production under basal conditions (3.5±1.2 vs 1.3±0.5 nmoles/min/mg protein with null vector controls) which was completely inhibited by pre-treatment with 10μM apocyanin, a Nox inhibitor. Inhibition of GRK2 by adenoviral-mediated expression of βARKct led to a significant reduction in ROS production and caspase 3 activity following H-R which was similar to that observed by knocking down Nox4. Immunoprecipitated Nox4 demonstrated a strong total serine phosphorylation under H-R conditions. Finally, confocal imaging of Nox4 and GRK2 in cardiac myocytes exposed to H-R demonstrated a primarily peri-nuclear co-localization that was absent under control normoxic conditions. These data provide evidence that GRK2 may be an important regulator of oxidative stress via NADPH oxidases in cardiac myocytes. Further investigation of this novel interaction between GRK2 and Nox4 will provide additional insight into the potential role of GRK2 as a regulator of oxidative stress and apoptotic signaling in the heart.
Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer.
Authors: M J O'Connell, J A Mailliard, M J Kahn, J S Macdonald, D G Haller, R J Mayer, H S Wieand
Journal: Journal of Clinical Oncology (1997)

PURPOSE The goal of this study was to determine the efficacy of intensive-course fluorouracil (5FU) plus low-dose leucovorin given for 6 months following potentially curative resection of colon cancer. PATIENTS AND METHODS Three hundred seventeen patients with high-risk stage II or stage III colon cancer were randomly assigned 3 to 4 weeks following surgery to receive either (1) chemotherapy with six cycles of 5FU (425 mg/m2) plus leucovorin (20 mg/m2) by rapid intravenous injection daily for 5 consecutive days every 4 to 5 weeks, or (2) observation. RESULTS The median follow-up duration is 72 months for patients still alive. Patients who received postoperative 5FU plus leucovorin experienced significant improvement in time to relapse (P &lt; .01) and survival (P = .02) compared with control patients treated with surgery alone. Stomatitis, diarrhea, and leukopenia were the predominant chemotherapy toxicities. There were no treatment-related deaths. CONCLUSION These results indicate that intensive-course 5FU plus low-dose leucovorin is effective in preventing tumor relapse and improving survival in patients with high-risk colon cancer. These benefits were seen with only six cycles of treatment, using low-dose leucovorin in combination with 5FU on a schedule convenient for outpatient administration.
Investigation of 20 non-HLA (human leucocyte antigen) psoriasis susceptibility loci in Chinese patients with psoriatic arthritis and psoriasis vulgaris
Authors: Q. Yang, H. Liu, L. Qu, X. Fu, Y. Yu, G. Yu, H. Tian, Y. Yu, D. Sun, J. Peng, F. Bao, C. Yuan, N. Lu, J. Li, Y. Zhang, F. Zhang
Journal: British Journal of Dermatology (2012)

Recently, a number of non-HLA (human leucocyte antigen) psoriasis genetic susceptibility loci have been identified through genome-wide association studies, but data on their association with psoriatic arthritis (PsA) are lacking.To investigate recently identified psoriasis susceptibility loci in a cohort of Chinese patients with PsA, psoriasis vulgaris (PsV) and healthy controls.Twenty single-nucleotide polymorphisms (SNPs) from 20 loci were selected for genotyping in 379 patients with PsA, 595 patients with PsV and 1181 healthy controls using the MassARRAY platform (Sequenom, San Diego, CA, U.S.A.). Data handling, quality control and association were performed using PLINK software, v. 1.07. The Cochran-Armitage trend test was used to test the genotype-phenotype association.PsA showed a significant association with markers at TNIP1 (rs17728338, P = 2.20 × 10(-8)), IL28RA (rs4649203, P = 5.04 × 10(-6)), IL12B (rs2082412, P = 3.82 × 10(-5)), ERAP1 (rs27524, P = 1.25 × 10(-3)), PTTG1 (rs2431697, P = 1.22 × 10(-3)) and GJB2 (rs3751385, P = 1.48 × 10(-3)) when compared with the control group. In PsV a significant association was found for IL28RA (rs4649203, P = 9.53 × 10(-7)), TNIP1 (rs17728338, P = 1.21 × 10(-4)) and ERAP1 (rs27524, P = 1.17 × 10(-3)). The allele frequencies were not statistically different between PsA and PsV except for SNPs at IL12B and ZNF816A with a nominal P-value of 0.04 and 0·01, respectively.This study provides evidence for the involvement of ERAP1, IL28RA, GJB2 and PTTG1 loci in PsA susceptibility and confirmed the previously reported association with PsA and PsV. These results support the hypothesis that genetic aetiology of psoriasis is the same in both PsA and PsV and also support the higher genetic component of PsA than PsV.
Relationship between cutaneous polyarteritis nodosa (cPAN) and macular lymphocytic arteritis (MLA): Blinded histologic assessment of 35 cPAN cases
Authors: Amandine Buffiere-Morgado, Maxime Battistella, Marie-Dominique Vignon-Pennamen, Adèle de Masson, Michel Rybojad, Antoine Petit, Florence Cordoliani, Edouard Begon, Béatrice Flageul, Alfred Mahr, Martine Bagot, Jean-David Bouaziz
Journal: Journal of the American Academy of Dermatology (2015)
Abstract 15822: Epidermacan: A Novel Stem Cell Derived Paracrine Factor Mediates Angiogenesis via Regulation of MicroRNAs
Authors: Ying Zhang, Pete Pow-anpongkul, Vinogran Naidoo, J.Alan Payne, Hui Mu, Richard E Pratt, Victor J Dzau, Maria Mirotsou
Journal: Circulation (2011)

Introduction:  MicroRNAs (miRNA) are small non-coding RNAs, which regulate gene expression and play an important role in cardiac hypertrophy, fibrosis, angiogenesis, and vessel remodeling. Previous work in our laboratory has demonstrated that mesenchymal stem cells genetically modified to overexpress Akt-1 (Akt-MSCs) promote cardiac repair by expressing enhanced levels of paracrine factors such as Sfrp2, Vegf and Igf-1. Here, we identify epidermacan, a novel protein, as secreted by Akt-MSCs and explore the hypothesis that it promotes angiogenesis via regulation of microRNAs.   Methods and Results:  Epidermacan is a glycosylated, disulfide-bonded secretory protein that contains fibronectin type III domains. A dramatic up-regulation of epidermacan mRNA in Akt-MSCs compared to control MSCs was revealed in microarray analysis, and was subsequently confirmed by quantitative RT-PCR. Epidermacan protein was present both in secreted form and membrane-associated form in cultured Akt-MSCs. His-tagged epidermacan recombinant protein produced in bacteria was used to study function of epidermacan  in vitro . Our data show that epidermacan promotes human umbilical vein endothelial cell attachment, proliferation and tube formation  in vitro . Further analysis using miRNA array profiling comparing epidermacan to known angiogenic factors VEGF and FGF revealed they shared a common miRNA signature. This list included known angiogenic miRNAs such as miR132, miR126*, miR424 and miR130a as well as novel miRNAs that were up-regulated by all three treatments.   Conclusion:  In conclusion, our data suggest that epidermacan is a novel stem cell derived paracrine factor that is up-regulated by Akt and promotes angiogenesis  in vitro . Treatment with epidermacan is associated with an increase in angiogenic miRNA expression similar to the one induced by VEGF and/or FGF treatment. Experiments are currently in progress to identify the key miRNAs modulating the epidermacan angiogenic effects  in vitro  and  in vivo .
Safety and Efficacy of Temozolomide in Patients With Recurrent Anaplastic Oligodendrogliomas After Standard Radiotherapy and Chemotherapy
Authors: Oliver-Louis Chinot, Stephane Honore, Henry Dufour, Maryline Barrie, Dominique Figarella-Branger, Xavier Muracciole, Diane Braguer, Pierre-Marie Martin, François Grisoli
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Most primary oligodendrogliomas and mixed gliomas (oligoastrocytoma) respond to treatment with procarbazine, lomustine, and vincristine (PCV), with response rates of approximately 80%. However, limited data on second-line treatments are available in patients with recurrent tumors. A novel second-generation alkylating agent, temozolomide, has recently demonstrated efficacy and safety in patients with recurrent glioblastoma multiforme and anaplastic astrocytoma. This study describes the effects of temozolomide in patients with recurrent anaplastic oligodendroglioma (AO) and anaplastic mixed oligoastrocytoma (AOA). PATIENTS AND METHODS: Forty-eight patients with histologically confirmed AO or AOA who had received previous PCV chemotherapy were treated with temozolomide (150 to 200 mg/m 2 /d for 5 days per 28-day cycle). The primary end point was objective response. Secondary end points included progression-free survival (PFS), time to progression, overall survival (OS), safety, and tolerability. RESULTS: Eight patients (16.7%) experienced a complete response, 13 patients (27.1%) experienced a partial response (objective response rate, 43.8%), and 19 patients (39.6%) experienced stable disease. For the entire treatment group, median PFS was 6.7 months and median OS was 10 months. For objective responders, median PFS was 13.1 months and median OS was 16 months. For complete responders, PFS was more than 11. 8 months and OS was more than 26 months. Response correlated with improved survival. Temozolomide was safe and well tolerated. Twelve patients developed grade 1/2 thrombocytopenia and three patients developed grade 3/4 thrombocytopenia. CONCLUSION: Temozolomide is safe and effective in the treatment of recurrent AO and AOA.
Personality pathology in recurrent depression: nature, prevalence, and relationship to treatment response
Authors: P A Pilkonis, E Frank
Journal: American Journal of Psychiatry (1988)

Personality assessments of 119 treatment-responsive patients with recurrent unipolar depression revealed that nearly half of the patients (48%) showed some personality disturbance. The most common personality features were avoidant (30.4%), compulsive (18.6%), and dependent (15.7%). Factor analyses of personality data in this homogeneous population yielded results that were consistent with previous factor analytic studies of personality features and clinical descriptions of depressed patients. Most notably, a discriminant function analysis using personality variables alone was able to distinguish (with 65% accuracy) between patients who responded normally to treatment and those who responded more slowly.
AURELIA: A randomized phase III trial evaluating bevacizumab (BEV) plus chemotherapy (CT) for platinum (PT)-resistant recurrent ovarian cancer (OC).
Authors: Eric Pujade-Lauraine, Felix Hilpert, Béatrice Weber, Alexander Reuss, Andres Poveda, Gunnar Kristensen, Roberto Sorio, Ignace B. Vergote, Petronella Witteveen, Aristotelis Bamias, Deolinda Pereira, Pauline Wimberger, Ana Oaknin, Mansoor Raza Mirza, Philippe Follana, David T. Bollag, Isabelle Ray-Coquard
Journal: Journal of Clinical Oncology (2012)

LBA5002^ The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Saturday edition of ASCO Daily News.
Most people with coverage through US health reform law are satisfied, survey finds
Authors: M. McCarthy
Journal: BMJ (2015)

A large majority, 86%, of people who obtained insurance through the US Affordable Care Act either by purchasing private plans through the insurance marketplaces created by the law or by enrolling through the expanded Medicaid program are very or somewhat satisfied with their coverage, says a report by the Commonwealth Fund, a non-partisan foundation that focuses on healthcare.

The finding that millions of these people are happy with their coverage poses a problem for Republicans who have vowed to repeal the law. …
Late-breaking abstract: The diaphragm and abdominal muscles act on the abdomen to displace blood to the extremities during exercise
Authors: Barbara Uva, Dario Bovio, Andrea Aliverti
Journal: European Respiratory Journal (2011)

We have recently demonstrated (Aliverti et al, J Appl Physiol, 2010) that during quiet breathing the diaphragm serves the double function to ventilate the lung and to shift blood from the splanchnic vascular bed to the extremities.  We hypothesized that with simultaneous contraction of abdominal muscles, such as occurs during exercise, the circulatory function of the diaphragm can be considerably enhanced.  Six healthy subject performed a submaximal constant exercise workload test (repeated foot flexion at ∼60% of max workload) within a whole body plethysmography (WBP) measuring changes in body volume (dVb). Simultaneously, changes in volume of the trunk (dVtr) were measured by optoelectronic plethysmography. Blood shifts between trunk and extremities (Vbs), were determined as dVtr-dVb.In all subjects, intra-breath variations of Vbs were bimodal. Vbs initially decreased and then increased during inspiration; Vbs then decreased in the first part of expiration, and increased again in the second part. After 1 min of exercise, within-breath tidal Vbs increased by 175±122 ml (p  We conclude that a precise control mechanism of the diaphragm and abdominal muscles determines intra-breath variations of Vbs during exercise. Due to the high frequency of tidal Vbs there is not adequate time for a complete refilling of the splanchnic blood reservoir at each abdominal compression, and this results into a significant shift of blood from the trunk to the extremities during exercise. When needed, this should be clinically useful.
Forced expiratory tracheal noise time in diagnostics of hidden bronchial obstruction among spirometry negative asthma patients
Authors: Irina Pochekutova, Veronika Malaeva, Vladimir Korenbaum
Journal: European Respiratory Journal (2011)

Computer instrumentation (Korenbaum et al., 2008) provides a precise estimation of acoustic tracheal forced expiratory noises time (FETa). The purpose was an estimation of FETa efficiency as diagnostic test of hidden bronchial obstruction (BO). The sample consisted of homogeneous groups: young male asthma (BA) patients as a BO model (71 persons with spirometry confirmed BA and 78 persons with spirometry negative BA), control group (77 non-smoking healthy subjects and 44 smokers). FETa values were normalized by C – chest circumference, H – height, M – body mass. Diagnostic thresholds were defined by ROC-analysis. Percentages of deviation from the norm, revealed by acoustic indicators in groups were evaluated.  Diagnostic efficiency of FETa and its normalized indicators in spirometry positive BA is very close to efficiency of base-line spirometry. Moreover, bronchial obstruction is acoustically diagnosed almost in a half of patients with spirometry negative BA, whereas healthy are indistinguishable from young smokers. Thus, FETa seems to be perspective for diagnostics of hidden bronchial obstruction, at least, in young male subjects. The study was supported by Far Eastern Branch of Russian Academy of Sciences grants No. 09-1-P21-08, No. 09-3-A-06-231.
Differences in chest HRCT between smoking and non-smoking rheumatoid arthritis patients with abnormal spirometry
Authors: Alexandre Kawassaki, Marianne Kawassaki, Daniel Pereira, Olivia Dias, Carlos Carvalho, Ronaldo Kairalla
Journal: European Respiratory Journal (2013)

INTRODUCTION: Smoking exposure is frequent in Rheumatoid Arthritis (RA) patients, but its role on RA lung disease is unknown. Obstructive lung disease may be secondary to cigarette smoking rather than to RA per se, but its frequency is still high in non-smokers with RA.  AIM: To compare and detect differences on chest high-resolution computed tomography (HRCT) between non-smoking RA patients and former or current smoking RA patients.  METHODS: Smoking and non-smoking RA patients with abnormal spirometry were submitted to chest HRCT. Readers classified patients in different lung patterns.  RESULTS: 61 RA patients with abnormal spirometry were analyzed, and 30 were non-smokers (49%). A total of six HRCT were considered normal or near normal, five in non-smokers. There was only one usual interstitial pneumonia and one non-specific interstitial pneumonia pattern. 17% non-smoking and 52% smoking patients were diagnosed as having chronic obstructive lung disease pattern (COPD) (p=0.002). 37% non-smoking and 19% smoking patients were diagnosed as RA-related airways disease pattern (p=0.06). Air trapping, bronchial wall thickening, and emphysema were observed in 47%, 80%, and 20% non-smoking patients, respectively; and in 45% (p=0.45), 87% (p=0.22), and 52% (p=0.005) smoking patients, respectively.  CONCLUSIONS: There was a statistically significant higher prevalence of COPD diagnosis in RA smoking patients than RA non-smoking patients, but COPD diagnosis was frequent in non-smokers. Emphysema was less frequently observed in non-smoking RA patients, but no pattern or HRCT abnormality could accurately differentiate between smoking and non-smoking RA patients with abnormal spirometry.
The epidemiology of invasive Streptococcus pneumoniae infections in onco-haematology and haematopoietic stem cell transplant patients in France. Are the serotypes covered by the available anti-pneumococcal vaccines?
Authors: K. Debbache, E. Varon, Y. Hicheri, P. Legrand, J-L. Donay, P. Ribaud, C. Cordonnier
Journal: Clinical Microbiology and Infection (2009)
Late-breaking abstract: Relationship of compliance to healthcare utilization outcomes and cost of home-telemonitoring for patients with lung cancer
Authors: Georgia L. Narsavage, Yea-Jyh Chen, Trisha Petitte, Kevin D Frick, Charles Coole, Tara Forth, Mohammed Almubarak, Joan Naim, Manish Monga
Journal: European Respiratory Journal (2014)

Aims: To study healthcare utilization/costs by compliance for Lung CA patients home-telemonitoring (TM) after feasibility (Petitte et al., ONF, 41(2), 153–161).

Methods: RCT 47 rural-patients (TM N=26; C N=21) with NSCLungCA: married, had smoked, HS educated, overweight BMI. RN-coached patients 14 days using TM-data. Healthcare use and cost (one-year direct medical cost) compared to baseline.

Results: 2-month study TM patients survived longer; had more unplanned calls to doctors/nurses (32% vs. 30% & 64% vs. 50%); fewer rehospitalizations (28% vs. 40%) and higher ER use (36% vs. 30%). TM compliant group had least ER visits/rehospitalizations (RH) of 3 subgroups (see figure: ER visit: 29% [30-50%; RH: 18% [40-50%)

![Figure][1] 



TM group had higher in-hospital costs prior to enrollment & during study; 4 months following-average TM costs lower (USD: $31,188 vs. $40,593). Lower costs (control) may relate to earlier deaths. TM group had relative improvements on health utility value (0.08; 0=death/1=perfect health)

Conclusions: Home TM in rural areas can decrease acute-care use for patients with lungCA but no significant impact on cost. Overall TM cost may be higher; improved life-quality may justify cost if TM limitations can be addressed. Findings limited by attrition/cost effects. Next: study with a larger sample to validate trends for positive patient & cost outcomes in rural areas.

(Funded NIH R15CA150999)

 [1]: pending:yes
Soluble mesothelin as a tool for early detection of malignant mesothelioma in asbestos-exposed workers
Authors: Kevin Hollevoet, Joris Van Cleemput, Joel Thimpont, Marc Vandeweerdt, Paul De Vuyst, Kristiaan Nackaerts, Joris Delanghe, Catherine Legrand, Jan P. van Meerbeeck
Journal: Journal of Thoracic Oncology (2009)
Airways and vascular remodelling in asthma and cardiovascular disease: implications for therapeutic intervention. Held in Napa, California, USA, May 1993
Authors: J Black, C Page
Journal: European Respiratory Journal (1994)

P.K. Jefferey, Structural Changes in Asthma. T. Cocks, Changes in Vascular Reactivity in Artherogenesis: Markers of Endothial Cell Dysfunction Associated with Initiation of the Disease. J.H. Campbell and G.R. Campbell, Vascular Smooth Muscle in Culture and its Relevance to the Study of Arthrogenesis. V. Lindner, In Vivo Investigations of Vascular Smooth Muscle Remodelling. M.J. Karnovsky and E.R. Edelman, Heparin/Heparan Sulphate Regulation of Vascular Smooth Muscle Cell Behaviour. M.I. Kotlikoff, Regulation of Cytoplasmic Calcium in Airway Smooth Muscle Cells: Implications for Growth and Contractility. J.G. Martin, Animal Studies with Drugs Affecting Airway Smooth Muscle Thickening. M. Okazawa, P.D. Pare, J.C. Hogg, and R.K. Lambert, Mechanical Consequences of Remodelling of the Airway Wall. A.J. Woolcock and J.K. Peat, Is Asthma a Reversible Disease? L.A. Laitinen and A. Laitinen, Anti-Inflammatory Therapy of Asthma: Corticosteroids. P. Konig, Anti-Inflammatory Therapy of Asthma: Non-Steroid Disease Modifying Agents. P. Gresele, Design of Large Multicentre Therapeutic Trials. The Relevance of the Cardiovascular Experience to the Design of Long Term Anti-Asthma Trials. Discussion Section. Subject Index.
Clinical criteria for psychiatric diagnosis and DSM-III
Authors: Robert L. Spitzer, Jean Endicott, Eli Robins
Journal: American Journal of Psychiatry (1975)

The authors identify the differences in formal inclusion and exclusion criteria used to classify patient data into diagnoses as the largest source of diagnostic unreliability in psychiatry. They describe the efforts that have been made to reduce these differences, particularly the specified criteria approach to defining diagnostic categories, which was developed for research purposes. On the basis of studies showing that the use of specified criteria increases the reliability of diagnostic judgments, they suggest that including such criteria in the next edition of APA's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) would improve the reliability and validity of routine psychiatric diagnosis.