tbuckley/cabot-search huggingface dataset:
Abstract 10394: Method to Measure the Valve Effective Orifice Area Following Transcatheter Aortic Valve Implantation
Authors: Marie-Annick Clavel, Josep Rodes-Cabau, Eric Dumont, Sebastien Bergeron, Rodrigo Bagur, Robert De Larochelliere, Daniel Doyle, Eric Larose, Philippe Pibarot
Journal: Circulation (2010)

Background: Transcatheter aortic valve implantation (TAVI) has emerged as an alternative to aortic valve replacement. To calculate the effective orifice area (EOA) of TAVI valves by continuity equa...
Radiation and Cisplatin activation of EBV in nasopharyngeal cancer: Understanding the oncolytic potential of EBV
Authors: Marie C. Chia, Abby Leung, Tiffaney Krushel, Nehad Alajez, Carlo Bastianutto, Fei-Fei Liu
Journal: Cancer Research (2006)

823  Introduction: The Epstein Barr Virus (EBV) is highly associated with Nasopharyngeal Cancer (NPC) where it exists in a state of latency (type II), expressing a limited number of genes. Upon stress activation however, the EBV profile switches to a lytic phase, associated with the expression of several critical EBV genes including BRLF1 and BZLF1. The events regulating this switch are not completely understood, but insights into this process may lead to the development of novel therapeutic strategies given the intimate relationship between EBV and NPC. Materials & Methods: The EBV positive cell line C666-1 was treated with ionizing radiation, RT (15Gy) and/or Cisplatin (50ug/mL). Gene expression data was determined using quantitative real-time PCR. Dominant-negative experiments were performed using dN-NF-YA (kindly provided by R. Manotvani) and over-expression analysis used the pNF-YA construct (Origene). Transactivation ability of NF-Y was determined on nuclear lysates using ELISA-based analyses (Active Motif). Chromatin immunoprecipiation (ChIP) experiments were performed using NF-YA and NF-YB antibodies (Active Motif, Santa Cruz) and primers designed for the appropriate NF-Y consensus regions. Results: C666-1 cells were treated with RT and/or Cisplatin, and a time and dose-dependent activation of BRLF1 and BZLF1 were observed. Increases in BRLF1 were observed as early as two hours post-treatment, followed by BZLF1 expression between 8 and 24 hours. The expression of both lytic genes increased in a time-dependent manner to 72 hours post-treatment. These same treatments were also associated with the increased expression of the transcription factor Nuclear Factor Y (NF-Y) and immediate nuclear transactivation. Introduction of dN-NF-YA significantly reduced BRLF1 expression after RT and Cisplatin treatment by 5-fold. Consistent with these observations, overexpression of NF-YA resulted in at least a 10-fold increase in both BRLF1 and BZLF1 expression. In silico analysis reveals that putative NF-Y consensus binding sequences are located in the promoter region of BZLF1 and BRLF1, suggesting a potential transcriptional regulatory role of NF-Y. Preliminary results using chromatin immunoprecipitation (ChIP) confirm the physical interaction between NF-Y and the promoter region of critical EBV lytic genes. Conclusion: Taken together, these data suggest the novel finding that NF-Y appears to be a major mediator of the EBV stress response in switching from a latent to lytic state. Manipulations which could increase NF-Y expression, thereby facilitating the expression of lytic EBV genes in human NPC, might offer a potential therapeutic strategy to enhance NPC response to RT and Cisplatin.
Abstract 1923: NPC1L1 Haplotype (1735C-25342A-27677T) is Related with Cholesterol Absorption from Intestine
Authors: Tomomi Maeda, Jun Kusano, Mineko Fujita, Daijiro Yasuda, Yoko Takeoka, Nakayuki Yoshimura, Toshio Ishikawa, Akira Honda, Yasushi Matsuzaki, Makoto Kinoshita, Tamio Teramoto
Journal: Circulation (2008)

Background: NPC1L1 is the intestinal sterol transporter that is a target molecule of ezetimibe. It has been reported that the LDL response to ezetimibe treatment is significantly different among NPC1L1 haplotypes. We hypothesized that common variants in NPC1L1 would affect cholesterol absorption from intestine and cholesterol synthesis in liver. Methods: Genomic DNAs were extracted from 140 healthy Japanese volunteers with informed consent. Three single nucleotide polymorphisms (SNPs) (1735C&gt;G, 25342A&gt;C, and 27677T&gt;C) were determined by PCR-RFLP method. Plasma concentration of lathosterol (a marker of cholesterol synthesis), and sitosterol, campesterol (markers of cholesterol absorption) were determined by LC-MS/MS for 79 subjects whose plasma was available. Results: NPC1L1 genotype frequencies of these SNPs of Japanese were as follows; 1735C/C:0.35, 1735C/G:0.464, 1735G/G:0.186; 25342A/A:0.969, 25342A/C:0.031, 25342C/C:0; 27677T/T:0.969, 27677T/ C:0.031, 27677 C/C:0. There were no significant differences in serum lipids concentration among three groups of 1735C/C, C/G, and G/G. Major haplotype of NPC1L1 in Japanese is 1735C-25342A-27677T, whose frequency is 0.573. Plasma concentration of campesterol of those who have at least one haplotype of 1735C-25342A-27677T is lower than those who dose not have 1735C-25342A-27677T, significantly (4.67±2.15 vs. 6.08±4.08 (p&lt;0.05)). Conclusion: NPC1L1 genotype frequencies are very different in Japanese populations from those reported in Caucasians. Those who have NPC1L1 haplotype 1735C-25342A-27677T had lower plasma campesterol concentration, which may indicate that cholesterol absorption is reduced in individuals with NPC1L1 haplotype 1735C-25342A-27677T. This may be the reason why ezetimibe is effective to lower LDL-cholesterol in individuals who lack this haplotype.
Clinicopathologic Characteristics of the EGFR Gene Mutation in Non–small Cell Lung Cancer
Authors: Anne S. Tsao, Xi Ming Tang, Bradley Sabloff, Lianchun Xiao, Hisayuki Shigematsu, Jack Roth, Margaret Spitz, Waun Ki Hong, Adi Gazdar, Ignacio Wistuba
Journal: Journal of Thoracic Oncology (2006)
Abstract 4291: Implantation of the Medtronic Melody Transcatheter Pulmonary Valve for Dysfunctional Right Ventricular Outflow Conduits: Clinical Results of Initial 99 Patients in the U.S. Investigational Device Exemption Trial
Authors: Julie A Vincent, William E Hellenbrand, Evan M Zahn, Thomas K Jones, John P Cheatham, James Lock, Doff B McElhinney
Journal: Circulation (2009)

Background: Enrollment into the prospective, non-randomized, 5-center, U.S. investigational device exemption trial for implantation of the Melody transcatheter pulmonary valve (TPV) for right ventr...
Human MGMT is a prime target for inactivation by oxidative stress, mediated by glutathionylation and oxidation of the active site cysteine145
Authors: Suryakant K. Niture, Chinavenmani S. Velu, Nathan Bailey, Kalkunte S. Srivenugopal
Journal: Cancer Research (2004)

1541  Both the antimutagenic and drug resistance properties conferred by the DNA repair protein, O6-methylguanine-DNA methyltranferase (MGMT) derive from its ability to transfer the alkyl groups bound to the O6-position of guanine on to a cysteine (cys145) at its active site. Because of the unique and reactive nature of this cysteine, and the possibility that cellular redox status may play a key role in maintaining this sulfhydryl group, we investigated the effect of glutathione and oxidative stress on the activity and biology of MGMT, using the UW228 human medulloblastoma cell line and recombinant MGMT (rMGMT) protein. Incubation of rMGMT or cell extracts with reduced glutathione (GSH) or GSSG (1-8 mM) resulted in potent inactivation of MGMT activity. This loss of activity occurred in a concentration- and time-dependent manner, and was reversed by dithiothreitol (DTT). Using biotinylated GSH as a probe and western analysis with streptavidin-linked horseradish peroxidase, we detected a rapid and specific incorporation of GSH into the MGMT protein, thereby, demonstrating that MGMT is a facile target for S-glutathionylation. Prior exposure of rMGMT with O6-benzylguanine (BG, 30 μM) or N-ethylmaleimide (2 mM) completely abolished the glutathionylation of MGMT, suggesting the active site cysteine to be the major site of modification. Further, the exposure of UW228 cells to various oxidants (H2O2, diamide, ter-butyl hydroperoxide, sodium hypochlorite) for 15 min induced a drastic loss of MGMT activity. rMGMT also showed a similar loss of activity on oxidant exposure; both cellular MGMT and rMGMT exhibited altered electrophoretic mobilities under these conditions. The glutathionylated and oxidized MGMT proteins were also susceptible for digestion by V8 protease, generating a specific 14 kDa peptide, not seen in unmodified MGMT digests, thus, confirming the existence of an altered conformational state in the modified proteins. In addition, we demonstrated the glutathionylation of cellular MGMT under physiological conditions by first treating the UW228 cells with oxidizing agents, and subsequently incubating them with the cell permeable biotinylated glutathione ethyl ester followed by affinity purification on avidin-agarose and western analysis. Other evidence indicated that oxidized and/or glutathionylated MGMT is specifically targeted for degradation through the ubiquitin-proteasomal pathway. These data provide the first evidence for the fine modulation of alkylation DNA damage and repair during oxidative stress, and show that MGMT is reversibly modified by S-thiolation. Although, a transient glutathionylation has been proposed as a protective mechanism to prevent enzyme inactivation, our results suggest that for MGMT, this process is likely to be futile, by targeting the protein for increased degradation (Supported by NIH RO1 CA97343 grant to KSS).
Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomised clinical trial
Authors: Debra Benator, Mondira Bhattacharya, Lorna Bozeman, William Burman, Antonino Catanzaro, Richard Chaisson, Fred Gordin, C. Robert Horsburgh, James Horton, Awal Khan, Christopher Lahart, Beverly Metchock, Constance Pachucki, Llewellyn Stanton, Andrew Vernon, M. Elsa Villarino, Cheng Wang Yong, Marc Weiner, Stephen Weis
Journal: The Lancet (2002)
5-azacytidine treatment results in myelodysplastic syndrome
Authors: S. M. Bakanay, E. Karakiliç, S. Civriz-Bozdag, M. Arat, M. Ozcan, G. Gurman, O. Ilhan, M. Beksac, N. Konuk, O. Arslan
Journal: Journal of Clinical Oncology (2009)

e18003 Background: Myelodysplastic syndrome (MDS) is a clonal disease of hematopoiesis characterized by dysplasia in one or more series. 5-azacytidine (5-AZA) which is one of the methyl transferase inhibitors, targets the epigenetic changes in MDS and has been used for the last few years. Phase III studies which compare 5-AZA with supportive therapies report response rates up to 60%. Methods: In this study the aim was to retrospectively analyze the response rates of 26 MDS patients who were treated with 5-AZA between years 2002–2008. The patients were; median age 58 (21–84); male/female = 16/10; RAEB-I (7 patients); RAEB-II (18 patients); ve CMML (1 patient); secondary MDS (2 patients). According to an international prognostic scoring system, 6 patients were intermediate-1; 9 patients were intermediate-2; and 11 patients were high risk. Nine patients received 5-AZA as first-line therapy. The median leukocyte counts, absolute neutrophil counts (ANC), hemoglobin values, and thrombocyte counts at the begining of the cycles were; 2.4 (0.5–23)x10e9/L, 0.7 (0.1–16.5)x10e9/L, 8.6(5.3–11.4) gr/dl, 41(4–35)x10e9/L, respectively. The karyotype analysis revealed del5q in 3 patients; -7/del7q in 6 patients; trisomy 8 in 7 patients, del20q, del11q and complex karyotype (del7q+del5q+delY) in 1 patient each. The median cycles completed were 2 (1–6). Results: Seven patient were not elligible for response evaluation. Nine patients (47%) did not respond to the therapy and 8 of them were lost. Ten patients (53%) responded to the therapy with complete remission (n=4), partial remission (n = 2) and hematological improvement (n = 4). The responders and non-responders were similar in terms of median age, sex and pretreatment leukocyte, ANC and hemoglobin levels. However, there was statistically significant difference in terms of initial thrombocyte counts, total number of cycles received and serum ferritin levels. The patients who received 5-AZA as first line therapy had beter response than others (71% versus 29%). Conclusions: The observed response to 5-AZA therapy was similar to the reported rates in the literature. The most important factors for response were initial thrombocyte counts, total number of cycles, other therapies received before 5-AZA and the serum ferritin levels. No significant financial relationships to disclose.
More recent data suggest guidelines are being adhered to
Authors: R. Martin, S. H. Ton, S. Kerry
Journal: BMJ (1995)

EDITOR,--J O Warner found that too few children were prescribed preventive treatment and too many were prescribed oral £ agonists in 1990-1.1 Though international paediatric guidelines had been distributed, the British Thoracic Society's guidelines were published later, in 1993. With more widespread dissemination of guidelines in general practice and incentives for asthma clinics, shared care, and audit, trends in prescribing in primary care have …
Abstract 2272: Three Year Survival of Drug-Eluting Stents versus Coronary Artery Surgery in Multivessel Coronary Disease
Authors: David J Malenka, Craig W Langner, John F Robb, Lawrence J Dacey, Mirle A Kellett, Reed D Quinn, M. Theodore Silver, Peter N Ver Lee, Robert A Clough, Micheal J Hearne, Benjamin M Westbrook, Matthew W Watkins, Bruce J Leavitt, Gerald T O’Connor
Journal: Circulation (2008)

Background. Several studies have compared survival following bare metal stenting (BMS) to coronary artery bypass grafting (CABG). Less is known about how survival following drug eluting stenting (DES), which compared to BMS has a lower risk of repeat revascularization and better survival, compare to CABG. Methods. From our Northern New England percutaneous intervention (PCI) and CABG registries we identified nonemergent multivessel disease patients who received a DES (n=2520) or underwent CABG (n=2626) in 2004 –2006 and compared 3-year survival through 2007. We adjusted for differences in baseline patient characteristics using Cox proportional-hazards models and propensity matching. Results. CABG patients had more diabetes, peripheral vascular disease, 3 vessel disease, and more complete revascularization. There was an increased early risk of death through 45 days that was higher for CABG than DES (Figure ). Following this early risk, the survival curves were linear, with a higher annual mortality rate for DES (4.1%/year) than for CABG (2.2%/year). The adjusted survival at 3 years for CABG (90.9%) was better that for DES (87.6%, p&lt;0.01). This finding was robust for all patient subgroups and after propensity matching. Conclusion . For patients with multivessel disease, survival at 3 years is better following CABG than DES, though the initial risk is higher with CABG.
Abstract 11031: Renal Function as Predictor of Mortality in Patients after Percutaneous Transcatheter Aortic Valve Implantation
Authors: Jan M Sinning, Alexander Ghanem, Hannah Steinhauser, Christoph Hammerstingl, Georg Nickenig, Nikos Werner
Journal: Circulation (2010)

Introduction: Acute kidney injury (AKI) occurs in up to 20% of all patients undergoing cardiac surgery (depending on the definition) and is associated with substantial morbidity and mortality independent of all other factors. Evidence is growing that renal function may also be major predictor of mortality in patients after transcatheter aortic valve implantation (TAVI). Hypothesis: The aim of this study is to determine the influence of baseline renal function and peri-procedural AKI on prognosis after TAVI. Methods: TAVI was performed with the 18F-CoreValve™ prosthesis via transfemoral access. All-cause mortality was determined 30 days and 6 months after TAVI. A total of 46 patients unsuitable for open heart surgery with a mean logistic EuroSCORE of 27.6 ± 18.0 % underwent TAVI. Results: Overall procedural success rate was 100% without periprocedural deaths. 30-day mortality was 13%, 6-month mortality was 24%. 48 hours after TAVI, a significant decrease of serum creatinine (P<0.001) and increase of estima...
Abstract P423: Six Minutes Walk Test in Patients with Severe Aortic Stenosis: A Maximal Exercise Testing Procedure?
Authors: Marjorie Bastien, Rodrigo H Bagur, Josep Rodes-Cabau, Audrey Auclair, Paul Poirier
Journal: Circulation (2013)

Rationale: Maximal exercise testing is an absolute contraindication in patients with severe symptomatic aortic stenosis (SSAS). Instead of maximal testing, the 6 minutes-walk test (6MWT) may be recommended to evaluate functional capacity and to establish prognostic. The aim of this study was to compare the 6MWT with a maximal exercise test in patients with SSAS. Method: A ramp cardiopulmonary exercise test (CPET) on a cycle ergometer taken as control, and a 6MWT, both with a breath-by-breath gas analysis, were performed in a population with SSAS waiting for transcatheter aortic valve implantation (TAVI). During both tests, patients were monitored with continuous electrocardiogram. Blood pressure was taken every 2 minutes during CPET and at the beginning and the end of the 6MWT test. Patients underwent both tests. Results: A total of 12 patients aged 79.5 ± 5.9 years participated to these evaluations. During the 6MWT, patients walked a mean distance of 335±74 m, producing a mean maximal workload of 48.5±13.2 watts during CPET. Through CPET, patients achieved a maximal oxygen consumption (VO2peak) of 11.9±4.2 mL/kg/min, which was similar to the VO2peak reached during 6MWT (12.8±2.5 mL/kg/min, p=0.062). For both tests, the respiratory exchanged ratio exceeded 1.1 (CPET=1.16±0.06 and 6MWT=1.12±0.09, p=0.241), which is one criterion of a maximal exercise capacity test. In comparison to CPET, a higher proportion of the 6MWT was performed at high intensity level (&gt;85% VO2peak); 74.2±29.0% of the 6MWT vs. 31.5±24.0% of CPET, p=0.004*. During CPET, 8 patients experimented abnormal blood pressure (BP) response (4 dropped their BP and 4 achieved maximal BP value during recovery). No complication occurred during both tests except for 3 patients who experienced angina pectoris. In this high-risk elderly cohort, lean body mass was the better anthropometric feature associated with better exercise capacity during CPET (r=-0.73, p=0.03*). Conclusion: Both exercise tests were very demanding for patients with SSAS waiting for TAVI. The 6MWT was a maximal effort and high intensity exertion was maintained for almost 75% of the test. The 6MWT was as intense as CPET suggesting the importance of an adequate monitoring while testing those patients. Considering that CPET allow blood pressure measure throughout the test and included a lower test portion in high intensity level, CPET may be more appropriate to evaluate functional capacity in patients with SSAS.
The addict, abstinence, and the family
Authors: J Schwartzman
Journal: American Journal of Psychiatry (1975)

The drug addict generally has an extremely difficult time terminating drug use and remaining abstinent. A partial explanation can be found in an investigation of the relative meaning of the drug for the addict within his social context rather than viewing the drug simply as a pharmacological agent. The idea that addiction is a social phenomenon within the addicts family suggests a relationship between the functioning of the families of addicts and their inability to tolerate abstinence. Because the abuse of heroin or barbiturates by one family member can result in "rewards" for all family members, the family, in behaving as if the addict cannot control his drug use, functions in such a way as to reinforce the addiction.
Manganese (II) Chelate Functionalized Copper Sulfide Nanoparticles for Efficient Magnetic Resonance/Photoacoustic Dual-Modal Imaging Guided Photothermal Therapy
Authors: Renfa Liu, Lijia Jing, Dong Peng, Yong Li, Jie Tian, Zhifei Dai
Journal: Theranostics (2015)

The integration of diagnostic and therapeutic functionalities into one nanoplatform shows great promise in cancer therapy.In this research, manganese (II) chelate functionalized copper sulfide nanoparticles were successfully prepared using a facile hydrothermal method.The obtained ultrasmall nanoparticles exhibit excellent photothermal effect and photoaoustic activity.Besides, the high loading content of Mn(II) chelates makes the nanoparticles attractive T 1 contrast agent in magnetic resonance imaging (MRI).In vivo photoacoustic imaging (PAI) results showed that the nanoparticles could be efficiently accumulated in tumor site in 24 h after systematic administration, which was further validated by MRI tests.The subsequent photothermal therapy of cancer in vivo was achieved without inducing any observed side effects.Therefore, the copper sulfide nanoparticles functionalized with Mn(II) chelate hold great promise as a theranostic nanomedicine for MR/PA dual-modal imaging guided photothermal therapy of cancer.
Enhancing the anticancer activity of paclitaxel through cyclin-dependent kinase inhibition
Authors: Philip C. Mack, Christopher M. Mahaffey, Paul H. Gumerlock, David R. Gandara
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

5434 

To develop strategies to enhance taxane-based therapies, we investigated the effects of cell cycle modulation on taxane efficacy. We and others have previously demonstrated that administration of paclitaxel followed by the cyclin-dependent kinase (cdk) inhibitor flavopiridol was synergistic. In that sequence, flavopiridol treatment resulted in an attenuation of paclitaxel-induced Cyclin B levels. We therefore hypothesized that an accelerated exit from taxane-induced M-phase arrest, via inhibition of the Cyclin B-Cdk1 complex, increases the anticancer activity of taxanes. Since flavopiridol has multiple targets beyond cdk inhibition that could account for the observed synergy, the selective cdk inhibitors roscovitine (ROS) and olomoucine (OLO) were employed in combination with paclitaxel to test this hypothesis. A549 cells were treated with 10nM paclitaxel for 24h and mitotic cells were collected and plated for colony formation assays. Cells were then treated with either ROS (1uM or 10uM) or OLO (50uM or 100uM) for 24h, or left without further treatment. Treatment with either agent resulted in significantly decreased colony formation compared to paclitaxel-only controls. ROS (10uM) decreased colony formation by over 40% (p<0.01) and OLO (100uM) by over 75% (p<0.001). A second set of experiments was conducted to determine whether mitotic cells are more sensitive than non-mitotic cells to the effects of flavopiridol in MCF-7 breast cancer cells. After paclitaxel treatment, mitotic and non-mitotic cells were separated and plated at equal densities. Half of the plates were subsequently treated with flavopiridol (200nM, 24h). In contrast to expectations, the mitotic fraction of paclitaxel-treated cells was over four times more viable than the non-mitotic fraction. However, flavopiridol treatment resulted in a 40% reduction in colony formation in the mitotic fraction (p<0.01) but had no significant effect on the non-mitotic fraction. Taken together, these data are supportive of our hypothesis that accelerated exit from taxane-induced M-phase arrest increases the anticancer activity of taxanes. It remains to be demonstrated whether Cdk1 inhibition results in a premature exit from M-phase, and if this exit is causative of the increased cell death. Further work will be conducted to determine the nature of the increased cytotoxicity (ie, apoptosis versus post-replicative cell death). (Supported by: ACS IRG 95-125-04 and UCD HSRA)