tbuckley/cabot-search huggingface dataset:
Abstract 11884: Successful Preclinical Study of Microporous Covered Stents for Intracranial Aneurysms
Authors: Yasuhide Nakayama, Tetsu Satow, Eika Hamano, Marina Funayama, Takeshi Mizuno, Hidetake Kawajiri, Takeshi Moriwaki, Daizo Ishii, Masataka Hayashi, Tsutomu Tajikawa, Jun Takahashi
Journal: Circulation (2014)

Introduction: Treatment of large or giant cerebral aneurysms with broad neck is extremely difficult or carries high risks, even with clinical available surgical method or endovascular one using coils with the assistance of bare stents. We are developing microporous covered stents (Goodman, Japan) for the treatment of intracranial aneurysms. In this study, as a preclinical study, their performances were evaluated in three different in vivo animal models under reliability assurance system (RAS). Methods and Results: The covered stents were prepared using specially designed flexible balloon-expandable stents (CoCr; diameter; 3.5~5.0 mm, length; 16~28 mm) by dip-coating to cover their strut completely with polyurethane membrane (thickness; 20 μm) followed by laser-based microprocessing (pore size; 100 μm, opening ratio; ~30%). All animal experiments were performed under RAS. 1) In canine curved vessel model (5 mm in diameter), all stents mounted on the derivery catheter could smoothly pass the tortuous vessel with little arterial damage (n=10). 2) In canine sidewall aneurysm model, all post-immediate run showed disappearance of the aneurysm (over 7 mm in size, 4 mm in wide), and histological examination at 3 months revealed complete endothelialization at the aneurysmal neck and entirely organized aneurysm (n=20). 3) In rabbit aortic model (3 mm in diameter), just after placing a single stent lumbar arteries (less than 1 mm) were patent with good run-off. Even after placing the second stent in an overlapped fashion lumbar arteries are still patent. After 3 months, both the parent artery and branching lumbar arteries are patent in all cases (n=15). The safety of the covering material was guaranteed at over 2 years (n=10). Conclusions: Excellent embolization performance was confirmed in all cases even at the large and wide-necked aneurysms on the tortuous vessels with high reliability. Based on the obtained perfect preclinical results we are planning the first in human study of the covered stents for intracranial aneurysms in 2015.
Enhanced pathological angiogenesis in mice lacking β3 integrin or β3 and β5 integrins
Authors: Louise E. Reynolds, Lorenza Wyder, Julie C. Lively, Daniela Taverna, Stephen D. Robinson, Xiaozhu Huang, Dean Sheppard, Richard O. Hynes, Kairbaan M. Hodivala-Dilke
Journal: Nature Medicine (2002)
Abstract #LB-155: Recombinant Listeria monocytogenes expressing HPV16 E7 induces E7-specific CD8+ T cells in a novel mouse model of human cervical cancer
Authors: Christopher Chiu, Ed Lemmens, Meredith Leong, Weiqun Liu, Peter Lauer, Bill Hanson, Thomas Dubensky, Doug Hanahan, Dirk Brockstedt
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Cervical cancer is the second most common malignant diseaseamong women worldwide. The causative agent of cervical cancer is a persistent infection with human papilloma virus (HPV) and, in particular, two of the high risk HPV, types 16 and 18, account for over 70% of cervical cancers. A mouse model of this disease affords opportunities to study mechanisms of cervical carcinogenesis, and to assess immunotherapeutic strategies. K14-HPV16 mice express the early region genes from HPV16 under the control of the human keratin 14 promoter (K14), restricting expression of the viral oncogenes to the basal squamous epithelium. Female mice (K14-HPV/E2) treated with sustained, low-dose estrogen synchronously develop cervical intraepithelial neoplastic (CIN) lesions that progress into cervical carcinomas, closely mimicking cervical cancer progression in humans. Given that there is a direct correlation with HPV infection and cervical cancer, there has been a long standing interest in the potential of eliciting productive immune responses against HPV to prevent as well as to resolve cervical neoplasias. Carcinogenesis is fully penetrant in this mouse model only on the FVB/n background. Although the H2q MHC of the FVB/n genotype cannot mount productive CD8+ T cell responses against the HPV16 oncoproteins E7 and E6, the K14-HPV16/E2 model has nevertheless proven to be a useful tool to assess immunotherapies directed against HPV16 E7, a biologically relevant tumor antigen. Seeking a more fully immunoreactive version of this mouse model of human cervical cancer, we generated a K14-HPV16 sub-line that is congenic for the H2b MHC locus (K14-HPV16/H2b). Here, we demonstrate that vaccination of K14-HPV16/H2b mice with a live-attenuated strain of Listeria monocytogenes (Lm) expressing HPV16 E7 (Lm \#916; actA /\#916; inlB HPV16 E7) elicited self-reactive E7-specific CD8+ T cells. The magnitude of the IFN-\#947;+ TNF\#945;+ E7-specific T cell response was increased with a boost vaccination and the elicited T cells effectively killed E7 loaded targets cells in vivo. Lm vaccine strains based on the same genetic attenuation (Lm \#916; actA /\#916; inlB ) have been evaluated in Phase I clinical trials under US IND for safety and tolerability in over 25 patients with chronic infection or malignant disease. Our findings demonstrate that a recombinant Lm strain expressing HPV16 E7 can overcome immune tolerance mechanisms in the K14-HPV16/H2b mouse. Immunotherapy trials in K14-HPV16/H2b mice are currently ongoing.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-155.
Sample Size Nomograms For Interpreting Negative Clinical Studies
Authors: Mark J. Young, Eddy A. Bresnitz, Brian L. Strom
Journal: Annals of Internal Medicine (1983)

In recent years there has been increasing attention to the appropriate interpretation of a clinical study. One special concern has been the difficulty inherent in interpreting studies that were not statistically significant: Was the sample size sufficient to detect a clinically important effect if, in fact, it existed? This concern is further complicated because readers may have differing opinions of what size effect is clinically important. A pair of sample size nomograms has been developed, using common levels of statistical significance, to assist in this interpretation. The nomograms are intended to provide the clinician with a handy and easy-to-use reference for ascertaining whether an apparently negative study has a sample size adequate to detect reliably any difference between treatment groups that the clinician believes is clinically important. Examples are provided to show these principles and the use of the nomograms in interpreting negative studies.
Abstract 12358: Abnormal Left Ventricular Midwall Fractional Shortening and Elevated Circulating Biomarkers Predict High Mortality in Elderly Individuals in the General Population
Authors: Serge Masson, Nera Agabiti, Gian Francesco Mureddu, Flavia Mayer, Vinzent Rolny, Tarcisio Vago, Ursula-Henrike Wienhues-Thelen, Alessandro Boccanelli, Roberto Latini
Journal: Circulation (2014)

Background: Individuals in the general population with a minimal elevation of cardiac biomarkers and left ventricular hypertrophy are at high cardiovascular risk and may be candidate for early strategies of prevention and treatment. We investigated the combination of several circulating biomarkers with abnormal midwall fractional shortening (MFS), an early echocardiographic indicator of preclinical systolic dysfunction, with adverse outcomes. Methods: Circulating levels of N-terminal probrain natriuretic peptide (NT-proBNP), high sensitivity cardiac troponin T (hs-cTnT), and intercellular adhesion molecule-1 (ICAM-1) were measured in 550 elderly community-dwelling individuals (65-84 years) from the PREDICTOR study. Participants were referred to cardiology centers for clinical examination and Doppler echocardiography with centrally-measured MFS. Causes of death or hospitalization were available after a median follow-up of 46 [39-54] months from record-linkage of administrative data. Results: Individuals with LV midwall dysfunction (MFS&lt;15%, n= 204 (38%)) had higher levels of NT-proBNP (148 [57-311] ng/L), hs-cTnT (7.3 [3.9-11.6] ng/L)and ICAM-1 (211 [177-261] ng/mL) than those with normal function (82 [42-171] and 5.0 [3.0-8.3] ng/L, 193 [165-230], respectively, p&lt;0.001). The cumulative incidence of total mortality (n=36) among individuals with abnormal MFS and elevated NT-proBNP (&gt;75th age- and sex-specific percentile) was 14% vs. 2% (abnormal MFS, low NT-proBNP), 6% (normal MFS, high NT-proBNP) and 1% (normal MFS, low NT-proBNP). Corresponding values for hs-cTnT (&gt; 3ng/L) were 14, 0, 5 and 3% (p&lt;0.0001) and 15, 5, 7 and 2% for ICAM-1 above median concentration (all p&lt;0.0001). After adjustment for sex, age, eGFR and hypertension, subjects with abnormal MFS and an elevated biomarker had a higher risk of total mortality compared to those with normal MFS and low biomarker: HR = 11.4 [1.5-87.7] (p=0.02) for NT-proBNP and 7.4 [2.1-25.6] (p=0.002) for ICAM-1, but not for hs-cTnT. Similar trends were seen for GDF-15. Conclusions: Elevation of circulating biomarkers combined with early alterations in LV systolic function with MFS identifies a subgroup of individuals in the general population aged 65 or more at higher risk for mortality.
Recalcitrant severe erosive cutaneous lichen planus treated with extracorporeal photopheresis monotherapy
Authors: R. Elewa, A. Altenburg, C.C. Zouboulis
Journal: British Journal of Dermatology (2011)

Journal Article Recalcitrant severe erosive cutaneous lichen planus treated with extracorporeal photopheresis monotherapy Get access R. Elewa, R. Elewa Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Centre, Auenweg 38, 06847 Dessau, Germany Search for other works by this author on: Oxford Academic Google Scholar A. Altenburg, A. Altenburg Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Centre, Auenweg 38, 06847 Dessau, Germany Search for other works by this author on: Oxford Academic Google Scholar C.C. Zouboulis C.C. Zouboulis Departments of Dermatology, Venereology, Allergology and Immunology, Dessau Medical Centre, Auenweg 38, 06847 Dessau, Germany Christos C. Zouboulis. E‐mail: christos.zouboulis@klinikum‐dessau.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 165, Issue 2, 1 August 2011, Pages 441–443, https://doi.org/10.1111/j.1365-2133.2011.10378.x Published: 01 August 2011
Emergency contraception
Authors: A. M C Webb
Journal: BMJ (2003)

Atrial by the World Health Organization published in 1998 established “levonorgestrel only” as the gold standard in hormonal emergency contraception.1 Over 80 countries have now approved dedicated emergency contraception products containing progestogen only, that are often available directly from pharmacies. Innovative strategies to improve access are also proliferating, expanding the ranks of those who can supply to nurses and other health workers, and offering supplies to women in advance. More recently, a further WHO trial has encouraged new flexibility in offering emergency contraception.2 Emergency contraception with levonorgestrel can now be given as “one stat” dose. However, women who need emergency contraception also have other needs, and a holistic sexual health service is essential.

The trial compared the effectiveness of the standard two dose regimen of 0.75 mg levonorgestrel repeated after 12 hours with the effectiveness of a double dose (1.5 mg levonorgestrel) taken all at once.2 Women in a third group took low dose (10 mg) mifepristone. Women could participate if they were able to start taking emergency contraception within 120 hours of unprotected intercourse, rather than just the traditional …
Interferon-gamma release assays (IGRA) for latent tuberculosis infection (LTBI) in children
Authors: Rizwan Ahmed, Deborah Gascoyne Binzi, Sandy Moffitt, Timothy Collyns, John Watson
Journal: European Respiratory Journal (2011)

Background:  IGRA, QuantiFERON®-TB Gold in-tube (QFT-GIT) & T-SPOT.TB®(T-Spot), are widely used to detect LBTI in adults. There is paucity of data regarding their use in children (   Methods:  We retrospectively reviewed all the IGRA tests performed in children, for contact & new entrant screening, in our TB service between 2008 & 2010, to look at our indeterminate rates.   Results:  A total of 188 IGRA tests were performed. T-Spot was undertaken almost exclusively in children under 1 year. None of our cohort had indeterminate IGRA results with QFT-GIT or T-Spot.  None of the children were diagnosed with active TB (multiple samples were sent for TB culture from 4 children).   Conclusion:  A definitive IGRA result is achievable in otherwise healthy children with close liaison between clinical and microbiology staff, prompt transfer of blood samples and incubating QFT-GIT samples within 4 hours of collection.   Reference:   1Ling, D.I. et al. Immune-based diagnostics for TB in children:what is the evidence?Paed Resp Reviews. 2011;12(1):9-15.
Inducible loss of NF-κB activity is associated with apoptosis and Bcl-2 down-regulation in Epstein-Barr virus-transformed B lymphocytes
Authors: Jean Feuillard, Marino Schuhmacher, Sylvie Kohanna, Marianne Asso–Bonnet, Frédérique Ledeur, Raymonde Joubert–Caron, Philippe Bissières, Axel Polack, Georg W. Bornkamm, Martine Raphaël
Journal: Blood (2000)
European Academy of Allergy and Clinical Immunology task force report on ‘dose-response relationship in allergen-specific immunotherapy’
Authors: M. A. Calderón, D. Larenas, J. Kleine-Tebbe, L. Jacobsen, G. Passalacqua, P. A. Eng, E. M. Varga, E. Valovirta, C. Moreno, H. J. Malling, E. Alvarez-Cuesta, S. Durham, P. Demoly
Journal: Allergy (2011)

To cite this article: Calderón MA, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng PA, Varga EM, Valovirta E, Moreno C, Malling HJ, Alvarez-Cuesta E, Durham S, Demoly P. European Academy of Allergy and Clinical Immunology task force report on 'dose–response relationship in allergen-specific immunotherapy'. Allergy 2011; 66: 1345–1359. Abstract Background: For a century, allergen-specific immunotherapy (SIT) has proven to be an effective treatment for allergic rhinitis, asthma, and insect sting allergy. However, as allergen doses are frequently adapted to the individual patient, there are few data on dose-response relationship in SIT. Allergen products for SIT are being increasingly required to conform to regulatory requirements for human medicines, which include the need to demonstrate dose-dependent effects. Methods: This report, produced by a Task Force of the EAACI Immunotherapy Interest Group, evaluates the currently available data on dose-response relationships in SIT and aims to provide recommendations for the design of future studies. Results: Fifteen dose-ranging studies fulfilled the inclusion criteria and twelve reported a dose-response relationship for clinical efficacy. Several studies also reported a dose-response relationship for immunological and safety endpoints. Due to the use of different reference materials and methodologies for the determination of allergen content, variations in study design, and choice of endpoints, no comparisons could be made between studies and, as a consequence, no general dosing recommendations can be made. Conclusion: Despite recently introduced guidelines on the standardization of allergen preparations and study design, the Task Force identified a need for universally accepted standards for the measurement of allergen content in SIT preparations, dosing protocols, and selection of clinical endpoints to enable dose-response effects to be compared across studies.
Abstract 17420: First Clinical Experience of Novel MRI Artifact Suppression Sequence in ICD Patients Undergoing Scar Delineation for Ventricular Tachycardia (VT) Ablation
Authors: Mohammed S Abdulghani, Ramazan Asoglu, T. Shin, R. Gullpalli, Rui Huang, Benjamin Remo, Tommas Klein, Ayman Hussien, Anastasios Saliaris, Vincent See, Stephen Synowski, Stephen Shorofsky, Jean Jeudy, Timm Dickfeld
Journal: Circulation (2014)

Background: Recent studies have suggested that CMR imaging can be safely performed in selected patients with implanted ICDs. However, metal artifacts significantly impact the evaluation of myocardial fibrosis when using standard late gadolinium enhanced (LGE) protocols. Methods: 10 continuous patients scheduled for VT ablation underwent LGE CMR imaging (1.5T Siemens Avanto) for scar delineation using either the standard clinical late gadolinium enhancement (LGE) sequences (n=5) or a novel MR pulse sequence that used an inversion preparation pulse with a wide inversion bandwidth of 2.4kHz (n=5). Results: Standard LGE MR sequences produced a large central signal void with surrounding hyperintensity due to voxel dephasing. The new wide inversion bandwidth sequence reduced the artifact in the right ventricle from 21±7% to 1.2±1.3% (p&lt;.001). Similarly, the new MRI sequence reduced the artifact in the LV from 44±9% to 4.5±5.7% (p&lt;.001). LV artifact location changed from 100% (inferior), 100% (septal), 100% (lateral) and 100% (anterior) to 0%, 0%, 0% and 60%, respectively. Similarly, the LV artifact present was present in the basal, mid and apical segment in 100%, 100%, and 100% in the old sequence but was reduced to 0%, 60%, and 20% in the new sequence (Fig.1). While the artifact of the standard sequence prevented the reliable predictions of the voltage-defined scar during VT ablation, no significant low voltage area outside the imaged LGE areas were found in the patients imaged with the new MRI sequence. Conclusions: Widening the inversion bandwidth achieves a dramatic reduction in ICD metal artifact during LGE CMR imaging and allows a near completely evaluation of the whole myocardium. This allowed the reliable prediction of low voltage areas during VT ablation despite presence of ICD.
Penetration of Serum Globulins into Mouse Tumors
Authors: R. Hiramoto, W. J. Nungester
Journal: Cancer Research (1958)

Summary  The injection of I131-tagged normal or immune globulin intravenously into mice bearing the Ehrlich tumor resulted in some increase in radioactivity in the tumor over that found in the spleen, liver, or kidney. The fluorescein-tagged normal and immune sera were not localized to any significant degree in the tumor. However, tumor cells could be made to fluoresce in vivo with tagged immune globulin, provided the cells were first injected intravenously and were trapped in the blood capillaries of the lung.
Abstract 13191: Short (2 hour) Intravenous Infusion of Purified Poloxamer-188 (MST-188) Elicits Prolonged (1-2 weeks) Improvement in Biomarkers in Dogs with Advanced Heart Failure
Authors: Hani N Sabbah, Ramesh Gupta, Marty Emanuele
Journal: Circulation (2014)

Background:  MST-188 (purified poloxamer 188) is a rheologic and membrane stabilizing agent shown to improve LV function in animals with experimental myocardial infarction or with dystrophin deficiency. Its activity likely results from improved microvascular blood flow and/or repair of damaged cell membranes. The latter can limit unregulated calcium entry into the cell and, therefore, calcium overload. We recently showed that 2 hour infusion of MST-188 also improves LV function in dogs with advanced HF with improvements lasting up to weeks post drug administration.   Hypothesis:  We tested the hypothesis that 2-hour infusion of MST-188 normalizes plasma biomarkers in dogs with HF (LV ejection fraction, EF ~30%) that include n-terminal pro-brain natriuretic peptide (nt-pro BNP), troponin-I (TnI), tumor necrosis factor-α (TNFα), interlukin-6 (IL-6), C-reactive protein (CRP), matrix metalloproteinase-2 (MMP-2) and pro-collagen 1 n-terminal peptide (PINP).   Methods:  21 HF dogs were randomized to 2 hours infusion of MST-188 (450 mg/kg, n=7 or 225 mg/kg, n=7)) or v/v normal saline (control, n=7). Plasma levels of biomarkers were measured using commercially available ELISA assays at baseline, at end of 2 hour infusion, and at 1 week and 2 weeks post-infusion.   Results:  Saline infusion in control dogs had no effect on any of the biomarkers. Treatment with both doses of MST-188 increased EF and reduced plasma levels of TnI, nt-Pro BNP, TNFα, IL-6, CRP and MMP-2 at 1 week and 2 weeks post-treatment in a dose-dependent manner but had no effect on PINP. Data (high dose MST-188 and saline control) are shown in the table.   Conclusions:  A 2 hour infusion of MST-188 in dogs with HF elicits improvements in key biomarkers of LV remodeling, cell death, inflammation and to a lesser extent collagen deposition that persisted for at least 2 weeks post-treatment. The findings support continued development of MST-188 for treatment of HF.
Basic fibroblast growth factor stimulates the proliferation of human dermal fibroblasts via the ERK1/2 and JNK pathways
Authors: T. Makino, M. Jinnin, F.C. Muchemwa, S. Fukushima, H. Kogushi-Nishi, C. Moriya, T. Igata, A. Fujisawa, T. Johno, H. Ihn
Journal: British Journal of Dermatology (2009)

Background Basic fibroblast growth factor (bFGF, FGF‐2) has been described as a multipotent cytokine that regulates cell growth as well as differentiation, matrix composition, chemotaxis, cell adhesion and migration in numerous cell types. It is known that bFGF stimulates proliferation of cultured fibroblasts. However, the detailed mechanism of fibroblast proliferation induced by bFGF in vitro still remains to be elucidated. Objectives We investigated the precise effects of bFGF on fibroblast proliferation and the signalling pathways responsible for bFGF‐induced proliferation in cultured human dermal fibroblasts (HDFs). Methods HDFs were cultured with bFGF in the presence or absence of specific inhibitors against MAPK signalling pathways including ERK, JNK and p38. The number of cells was counted and immunoblotting findings were examined for the activation of ERK1/2 and JNK. Furthermore, the inhibitory effects of ERK1, ERK2 and JNK1 were proven by the transfection of siRNA. Results bFGF increased the number of HDFs in a dose‐ and time‐dependent manner. The bFGF‐induced proliferation was suppressed by the MEK inhibitors PD98059 and U0126, and the JNK inhibitor SP600125. bFGF increased the phosphorylation levels of ERK1/2 and JNK1. Treatment with ERK1, ERK2 or JNK1 siRNA significantly inhibited bFGF‐induced proliferation. Conclusions This study indicates that ERK1/2 and JNK pathways play an important role in the bFGF‐mediated effect in HDFs. This study also suggests that controlling ERK1/2 and/or JNK signalling may therefore be a new therapeutic approach for the treatment of chronic and untreatable skin ulcers.