tbuckley/cabot-search huggingface dataset:
848. The Study on the VEGF Plasmids Purify by Magnetic Nanoparticles
Authors: Tomasz H. Kowalczyk, Christopher R. Gedeon, Patrick J. Klepcyk, Sharon M. Oette, Tamara L. Fink, Robert C. Moen, Mark J. Cooper
Journal: Molecular Therapy (2004)

In order to evaluate the usefulness of circular dichroism (CD) spectroscopy as a quality control assay in manufacturing DNA nanoparticles, well-characterized complexes consisting of single molecules of plasmid DNA condensed with lysine polymers were spectrally analyzed. Plasmids of various sizes encoding luciferase (pLuc: 5.3, 9.7, and 20.2 kbp) or green fluorescent protein (pGFP: 2.9, 5.1, and 28 kbp) were condensed at a final 2:1 charge ratio (+to-) using conjugates of 10 kDa polyethylene glycol (PEG)-substituted 30-mer lysine polymers having an N-terminal cysteine. At the time of DNA mixing, the polylysine counterions were either acetate or trifluoroacetate, which determine nanoparticle shape (rods or ellipsoids, respectively). The condensed plasmids were characterized by electron microscopy (DNA nanoparticle size and shape), turbidity and sedimentation assays (colloidal stability), serum stability tests (protection of DNA from nucleases), and gel analysis (DNA integrity). CD spectra for condensed DNA, free DNA, and free polylysine were recorded at 4 deg C over a wavelength range of 195-310 nm. Free polylysine had a random coil conformation with a peak at 215-219 nm. This conformation was apparently preserved after binding to DNA since the strong positive ellipticity peak at 200 nm, which is characteristic of α and βconformations, was not observed in the compacted DNA. The CD spectra for condensed pLuc 5.3 kbp plasmid in water, 0.15 M NaCl, or 0.3 M NaCl were almost identical and distinct from the spectra for free DNA. The native 280-nm peak of B-form DNA decreased and red-shifted, as did the 261-nm crossover point, and the troughs at ~200 nm and ~250 nm became more negative. Electron microscopy and sedimentation analyses of DNA nanoparticles in water, 0.15 M NaCl, or 0.3 M NaCl were identical, showing unaggregated unimolecularly compacted DNA. At 0.5 M NaCl, however, DNA nanoparticles demonstrated aggregates of partially condensed DNA. Interestingly, CD spectra of DNA nanoparticles at 0.5 M NaCl were typical of psi-form DNA, which has significantly enhanced peaks at 220 nm and 280 nm and a reduced trough at 250 nm. At 1 or 1.5 M NaCl, the CD spectra for condensed DNA were a sum of spectra for free polylysine and free DNA. This expected result is consistent with complete dissociation of those two components, as revealed by titration of free lysine residues with fluorescamine. Qualitatively, spectra of all non-aggregated condensed plasmids (irrespective of plasmid size, reporter gene, and polylysine counterion) showed unique and common features distinguishing them from free DNA, aggregates of partially neutralized DNA, and other aggregates reported in the literature as having psi-type spectra. The unique spectrum and reproducibility of this test makes CD a useful quality control assay in monitoring the production of unimolecularly-compacted DNA nanoparticles.
Abstract 1113: Autologous Bone Marrow Mononuclear Cell (ABMMC) injection Tc99m-HMPAO post Acute Myocardial Infarction: Conparison of two delivery techiniques
Authors: Hans Dohmann, Suzana Silva, Fabio Tuche, Andre a Haddad, Rodrigo Moreira, Andre Sousa, Jader Azevedo, Jose Hugo Luz, Claudio Tinoco, Cintia Peixoto, Monica Amorim, Radovan Borojevic
Journal: Circulation (2007)

Purpose: Dinamic behavior of transplanted ABMMC is probably a crucial determinant of its beneficial effects. We aimed to indirectly evaluate cell engraftment of labeled cells and its correlation wi...
Abstract 16709: Contrasting Influences of Renal Function on Blood Pressure and HbA1c Reductions With Empagliflozin in Patients With Type 2 Diabetes and Hypertension
Authors: David Cherney, Mark Cooper, Ilkka Tikkanen, Susanne Crowe, Odd Erik Johansen, Søren S Lund, Hans J Woerle, Uli C Broedl, Thomas Hach
Journal: Circulation (2014)

The sodium glucose cotransporter 2 inhibitor empagliflozin (EMPA) reduces HbA1c, weight and blood pressure (BP) in patients with type 2 diabetes (T2D). While glucose lowering with EMPA is dependent on renal function, the impact of chronic kidney disease (CKD) on BP reduction with EMPA is less well understood. Our aim was to determine if impaired renal function attenuates antihypertensive effects of EMPA. A Phase III randomized placebo (PBO)-controlled trial (EMPA-REG BP™) investigated the efficacy and safety of EMPA in patients with T2D and hypertension (defined as mean seated office systolic BP [SBP] 130-159 mmHg and diastolic BP [DBP] 80-99 mmHg at screening). Patients (mean [SD] age 60.2 [9.0] years, HbA1c 7.90 [0.74] %, 24-hour SBP 131.4 [12.3] and 24-hour DBP 75.0 [7.8] mmHg) received EMPA 10 mg (n=276), EMPA 25 mg (n=276) or PBO (n=271) once daily for 12 weeks. We assessed changes from baseline in mean ambulatory 24-hour SBP and HbA1c in subgroups by baseline eGFR (MDRD equation), adjusting for differences in baseline mean 24-hour SBP (for SBP analyses only), HbA1c, region, number of antihypertensive medications, treatment, eGFR and treatment by eGFR interaction between groups. In patients with normal renal function, or stage 2 or 3 CKD, EMPA significantly reduced HbA1c and mean 24-hour SBP vs PBO (Table). As expected, PBO-corrected HbA1c reductions with EMPA appeared to decrease with decreasing eGFR (Table). In contrast, PBO-corrected reductions in mean 24-hour SBP with EMPA mostly appeared to increase with decreasing eGFR (Table). Unlike HbA1c, mean 24-hour SBP reductions with EMPA in patients with T2D and hypertension appear to be greater in patients with lower eGFR, indicating that SBP modulation with EMPA may involve pathways other than urinary glucose excretion such as diuretic effects, weight loss, improved glycemic control, reduced arterial stiffness or direct vascular effects.
Mutations in the human Delta homologue, DLL3, cause axial skeletal defects in spondylocostal dysostosis
Authors: Michael P. Bulman, Kenro Kusumi, Timothy M. Frayling, Carole McKeown, Christine Garrett, Eric S. Lander, Robb Krumlauf, Andrew T. Hattersley, Sian Ellard, Peter D. Turnpenny
Journal: Nature Genetics (2000)
Complexity science: Complexity, leadership, and management in healthcare organisations
Authors: P. E Plsek, T. Wilson
Journal: BMJ (2001)

The number of patients coming to hospital with liver disease is increasing. There was a worrying trend before the pandemic, and this has intensified. Despite improvements in the management of patients with advanced cirrhosis many patients will die within 6–12 months of first presentation, and, despite this, the field of palliative and supportive care in liver disease is still in its infancy. This is a narrative review. Evidence is often thin in this field. Where it exists it is cited, but much of the commentary here is based on the authors own experience and readers are free to consider it and debate it. Most patients who die of liver disease receive palliative care very late in their illness (if at all). There are many barriers to supportive and palliative care in liver disease which are discussed. Symptom control is often poor because of these barriers. Before symptomatic control can be established, patients in need of it must to be identified and conversations had about the severity of their situation and what their wishes would be. Interest in palliative and supportive care for patients liver disease is growing as is the number of hepatologists and palliative care clinicians within the UK with an interest. It is important that this enthusiasm and interest can be rolled out and scaled up across the UK so that all patients, wherever they are, can benefit. The aims of these articles are first to highlight and bring into focus the unmet need for palliative and supportive care in liver disease and second to provide suggestions for its integration into liver services. Ask yourself the question: where would I start in my hospital to help these patients?
Abstract 5563: Docetaxel-induced mucositis in breast cancer patients: Association with plasma alpha-1-acid glycoprotein level and SLCO1B3 genotype
Authors: Rafid S. Jabir, Gwo F. HO, Muhammad Azrif A. Anuar, Johnson Stanslas
Journal: Cancer Research (2014)

Abstract Mucositis is one of the major non-hematological adverse effects (AEs) of docetaxel, besides fatigue, nausea, vomiting, diarrhea and rash which limit its use in cancer patients. Alpha-1-acid glycoprotein (AAG) is an acute phase reactant glycoprotein and is a primary carrier of docetaxel in the blood. Docetaxel demonstrates extensive binding to plasma proteins (&amp;gt;98%) including AAG, lipoproteins and albumin. However, there is a remarkable inter-individual variation of AAG level among cancer patients. Low plasma AAG levels will result in excessive free drug in the circulation, which in turn causes more AEs. Consequently, either the dose is reduced or treatment modality is diverted. In addition, single nucleotide polymorphisms (SNPs) of genes encoding for proteins involved in the transport of docetaxel (SLCO1B3) could lead to reduced clearance and accumulation in the circulation and subsequent AEs. Hence, we investigated 91 Malaysian breast cancer patients receiving docetaxel as a single agent chemotherapy at 90-100 mg/m2 and 75 mg/m2 in the adjuvant and metastatic settings respectively, to determine the association between the SNP (SLCO1B3 334TG), plasma AAG level and docetaxel AEs. The plasma AAG level was determined using Enzyme Linked Immunosorbent assay (ELISA) technique, while the SNPs were analyzed using PCR-RFLP technique followed by DNA sequencing of selected samples. The patients consisted of 49 Chinese (54%), 34 Malays (37%) and 8 Indians (9%). We found a significant difference in plasma AAG level between patients with mucositis and those without (178±74 mg/dl vs 225±97 mg/dl,P&amp;lt;0.05). Moreover, patients with mutant SLCO1B3 334GG who developed diarrhea also had mucositis (p&amp;lt;0.05). In conclusion, patients with lower plasma AAG level are more susceptible to develop mucositis. In addition, patients carrying mutant SLCO1B3 334GG who have diarrhea tend to develop mucositis concurrently. Plasma AAG level and SNPs could serve as potential predictive biomarkers of docetaxel-induced mucositis.We would like to thank Malaysian Ministry of Higher Education (MOHE) and University Malaya for funding this project through FRGS (04-04-10-848FR) and HIR (UM.C/625/1/HIR) grants. Citation Format: Rafid S. Jabir, Gwo F. HO, Muhammad Azrif A. Anuar, Johnson Stanslas. Docetaxel-induced mucositis in breast cancer patients: Association with plasma alpha-1-acid glycoprotein level and SLCO1B3 genotype. [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 5563. doi:10.1158/1538-7445.AM2014-5563
Abstract CT126: Phase II study of CEPSP chemotherapy for newly diagnosed stage IV extranodal natural killer (NK)/T-cell lymphoma, nasal type
Authors: Jun Zheng, Yajun Zhao, Hui Xue, Xiufeng Bai, Ke Wang, Mengqi Zhang, Chanyuan Du, Shuyang He, Xiaoming Wang, Sanhu He, Moyi Sun, Gang Li
Journal: Cancer Research (2015)

Abstract Purpose: Extranodal natural killer (NK)/T-cell lymphoma, nasal type (ENKL) is rare, it takes longer to make a definite diagnosis when compared with other head and neck malignancy, and its standard therapy has not been well established. To explore a more effective treatment for newly diagnosed stage IV ENKL, we conducted a phase II study of the Cisplatin + Etoposide + Pingyangmycin + Semustine + Prednisone (CEPSP) regimen. Patients and Methods: We retrospectively reviewed the medical records of 21 patients diagnosed with ENKL who were enrolled to our hospital between January 1993 and June 2013. Patients with newly diagnosed stage IV and a performance status of 0 to 2 were eligible. Two cycles of CEPSP chemotherapy via temporal shallow artery intubation were administered as the protocol treatment with little adjustment in individual. The primary endpoints were overall response rate (ORR) and complete remission rate after the protocol treatment. The secondary endpoints were 3-year overall survival, 3-year progression-free survival, and toxicity. Results: A total of 21 eligible patients were enrolled. The median age was 41 years (range, 20 to 69 years), and the male vs female ratio was 13:8. The disease status was newly diagnosed stage IV in 21 patients. The eligibility was revised to include lymphocyte counts of 500/μL or more because the first patient died from myelosuppression. No treatment-related deaths were observed after the revision. The ORR and complete remission rate after two cycles of CEPSP chemotherapy were 86% (92% CI, 61% to 85%) and 63%, respectively. In the 21 patients who completed the protocol treatment, 7 underwent blood component transfusion. The 2-year overall survival rate was 68% (93% CI, 41% to 65%). Grade 4 neutropenia was observed in 89% of the patients. The most common nonhematologic complication was gastrointestinal reaction (58%). Conclusion: CEPSP chemotherapy via temporal shallow artery intubation is an effective treatment for newly diagnosed stage IV ENKL. During the period of treatment, myelosuppression and gastrointestinal reaction should be treated carefully. Citation Format: Jun Zheng, Yajun Zhao, Hui Xue, Xiufeng Bai, Ke Wang, Mengqi Zhang, Chanyuan Du, Shuyang He, Xiaoming Wang, Sanhu He, Moyi Sun, Gang Li. Phase II study of CEPSP chemotherapy for newly diagnosed stage IV extranodal natural killer (NK)/T-cell lymphoma, nasal type. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT126. doi:10.1158/1538-7445.AM2015-CT126
Efficient identification of mouse models of human congenital cardiopulmonary malformations using high-throughput magnetic resonance imaging
Authors: J E Schneider, J Base, A W Hart, S D Bamforth, A D Gruber, C Broadbent, K Clarke, S Neubauer, S H Cross, I J Jackson, A Lengeling, S Bhattacharya
Journal: Circulation (2004)
Abstract 18720: The Impact of Prolonged Clopidogrel Use Beyond 12 Months After Coronary Stenting in Smokers and Non-smokers
Authors: Jeremiah P Depta, Kyle Smoot, Kelly Cho, Galina Sokolovskaya, David R Gagnon, Samantha Ly, Sara Temiyasathit, Jacquelyn Do, Adrianna Nava, Simon Ostrowski, Michael Gaziano, David P Faxon, Scott Kinlay
Journal: Circulation (2014)

Background: Cigarette smoking potentiates the antiplatelet effect of clopidogrel. Guidelines recommend clopidogrel for 12 months after percutaneous coronary intervention (PCI) with bare-metal (BMS) or drug-eluting (DES) stents. Whether smoking affects the risk of ischemic events related to clopidogrel use beyond 12 months after PCI is unknown Methods: We identified all PCIs performed in the Veterans Affairs (VA) health system from 2002-2006 and linked the information with the VA pharmacy database. VA and non-VA clinical outcomes were identified by ICD-9 codes from the VA National Patient Care and CMS/Medicare databases. All patients who were event-free at 12 months were followed for death, myocardial infarction (MI), or target vessel revascularization (TVR) up to 4 years following PCI. Prolonged (i.e., &gt; 12 months) vs. clopidogrel use for &lt; 12 months was assessed for each outcome within each stent type using propensity score adjusted inverse probability of weighting (IPW) Cox-proportional hazards analyses. Results: From 2002-2006, 28,507 patients included in the study underwent PCI and were event free at 12 months. Of these, 42% were smokers (n = 11,989) at the index PCI, 51% received a DES (n = 14, 594) and 45% were treated with prolonged clopidogrel use (n = 12,968). Following a 12-month landmark period, 2,194 deaths, 2,288 death or MIs, and 2,010 TVRs occurred. In smokers, prolonged clopidogrel use was associated with a lower risk of death and death or MI with both stent types (interaction p ≤ 0.10). In non-smokers, prolonged clopidogrel use was associated with a lower risk of death (interaction p = 0.04) and death or MI (interaction p = 0.03) in patients receiving DES only (Table). Conclusions: Prolonging clopidogrel more than 12 months after PCI may lower the risk of death or MI in smokers irrespective of stent type and in non-smokers receiving DES only. This study suggests that the duration of clopidogrel use after PCI may be tailored to smoking status and stent-type.
Seasonal Hay Fever Not Due to Pollen
Authors: Samuel M. Feinberg
Journal: Annals of Internal Medicine (1930)

Article1 April 1930Seasonal Hay Fever Not Due to PollenSAMUEL M. FEINBERG, M.D.SAMUEL M. FEINBERG, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-3-10-1035 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptIt is now an accepted fact that the majority of seasonal hay fever cases can be benefited by proper treatment with pollen extracts. It is also a very common observation, however, that there are many failures in such treatment. In a previous communication1 I have called attention to some of the common reasons for failure to obtain satisfactory results. These were chiefly the failure to pay attention to: early preseasonal, combined with seasonal treatment; individualization of pollen dosages; preservation of potency of pollen; and careful determination of the species of pollen to be used in treatment.In addition to the...Bibliography1 FEINBERG SM: Hay Fever Treatment, Factors Leading to Maximum Results, Clin. Med. & Surg., May, 1928. Google Scholar2 BALYEAT RM: Secondary Factors in Uncomplicated Cases of Seasonal Hay Fever, Based on a Study of 719 Cases. J. Lab. & Clin. Med., 14:617, April, 1929. Google Scholar3 BALYEAT RM: Importance of Orris Root as Etiologic Factor in Hay Fever and Asthma; based on a Study of 1,000 cases of Hay Fever and Asthma. J. Lab. & Clin. Med. 13:516, March, 1928. Google Scholar4 PHILLIPS EW: Orris Coryza, Southwest. Med. 11:299, July, 1927. Google Scholar5 SPAIN WC: The Diagnosis and Treatment of Atopic Coryza, Annals Otol. Rhin. & Laryng. 34:1089, 1925. CrossrefGoogle Scholar6 BALYEAT RM: Perennial Hay Fever; Diagnosis and Treatment based on a Study of 441 Cases, South. Med. J. 22:492, May, 1929. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *From the Asthma and Hay Fever Clinic, Northwestern University Medical School. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byReview of the hay fever literature of 1929 1 April 1930Volume 3, Issue 10Page: 1035-1037KeywordsAsthmaFeversPollen ePublished: 1 December 2008 Issue Published: 1 April 1930 PDF downloadLoading ...
Abstract P342: Periodontal Bacteria, Prevalent Prediabetes and Plasma Glucose Progression: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS)
Authors: Ryan T Demmer, David R Jacobs, Richa Singh, Aleksandra Zuk, Michael Rosenbaum, Panos N Papapanou, Moïse Desvarieux
Journal: Circulation (2015)

Introduction: Periodontal infections have been hypothesized as a cardiometabolic risk factor. The relationship between periodontal microbiota and early diabetes risk has not been studied. Hypothesis: We hypothesized that periodontopathic bacteria would be associated with both prevalent pre diabetes and accelerated longitudinal plasma glucose progression among diabetes-free adults. Methods: The Oral Infections, Glucose Intolerance and Insulin Resistance Study (ORIGINS) enrolled 300 diabetes-free adults (77% female) aged 20-55 years (mean=34±10). Prevalent prediabetes was defined as: i) 5.6%&lt;HbA1C&lt;6.5%; or ii) 99 mg/dL&lt;fasting plasma glucose (FPG)&lt;126 mg/dL. In 1,188 subgingival plaque samples, 11 bacterial species including Aggregatibacter actinomycetemcomitans (Aa), Porphyromonas gingivalis (Pg), Treponema denticola (Td), Tannerella forsythia (Tf) and Actinomyces naeslundii (An) were assessed at baseline. Modified Poisson regression evaluated prediabetes prevalence across bacterial tertiles. Risk ratios (RR), 95% confidence intervals (CI) for 3rd vs. 1st tertile are presented. Follow-up is ongoing but longitudinal FPG was available for interim analysis among the first n=100 recall-eligible participants (mean follow-up time=2±0.3 years). Mixed-effects regressions evaluated FPG time trends across baseline bacterial levels. All analyses were adjusted for cardiometabolic risk factors. Results: Prediabetes prevalence was 18% (54 of 300). RRs(95%CI) summarizing associations between bacteria and pre diabetes were as follows: Aa=2.48[1.34,4.58], p=0.004; Pg=3.41[1.78,6.58], p=0.0003; Td=1.99[0.992,4.00], p=0.052 and Tf=1.95[1.0,3.84], p=0.05; An=0.46[0.25,0.85], p=0.01. Among participants with high baseline values of Pg or Tf, FPG increased by ~2.5 mg/dl during follow-up (all p-values&lt;0.05) while no FPG progression was observed among participants with low baseline bacterial levels. Conclusion: Periodontopathic microbiota are associated with both prevalent prediabetes and longitudinal plasma glucose increase among diabetes-free adults.
Incidence of Cardiovascular Risk Factors in an Indian Urban Cohort
Authors: Mark D. Huffman, Dorairaj Prabhakaran, Clive Osmond, Caroline H.D. Fall, Nikhil Tandon, Ramakrishnan Lakshmy, Siddharth Ramji, Anita Khalil, Tarun Gera, Poornima Prabhakaran, S.K. Dey Biswas, K. Srinath Reddy, Santosh K. Bhargava, Harshpal S. Sachdev
Journal: Journal of the American College of Cardiology (2011)
Abstract 4453: Synergistic anticancer effect of combination of AZD6244 and BYL719 targeting KRAS mutant in non-small cell lung cancer
Authors: Eun Hye Jho, Sin I. Kang, Yeon-Hee Bae, Young Mee Park, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn
Journal: Cancer Research (2014)

Abstract KRAS mutation is found in 10-30% of non-small cell lung cancer (NSCLC) and highly correlated with smokers. So far, targeted agents demonstrating therapeutic activity against K-ras mutation are not available in a clinical setting. In this study, we show that dual agents, MEK inhibitor, AZD6244, and PI3K inhibitor, BYL719, have a synergistic effect on only KRAS mutant NSCLC cells. We defined that the combination of AZD6244 and BYL719 at ratios of IC50 1/2:1/2, 1:1, 2:2 (μM / μM) has ratio-dependent synergistic effect. In vitro, the combination of AZD6244 and BYL719 potently inhibited cell proliferation with cytotoxicity in H2009 and A549 cells more than the same cells treated with single drug. Also, BYL719 enhanced AZD6244-induced apoptosis and the combination treatment induced cleavage-PARP and Bim overexpression. In vivo, the antitumor efficacy was potentiated by co-treatment of AZD6244 and BYL719 in A549 xenografts. These data suggest that the combination of MEK and PI3K inhibitors might be a candidate for clinical development for its synergistic effect against KRAS-driven lung cancer. Citation Format: Eun Hye Jho, Sin Il Kang, Yeon-Hee Bae, Young Mee Park, Jong-Mu Sun, Jin Seok Ahn, Keunchil Park, Myung-Ju Ahn. Synergistic anticancer effect of combination of AZD6244 and BYL719 targeting KRAS mutant in non-small cell lung cancer. [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 4453. doi:10.1158/1538-7445.AM2014-4453