tbuckley/cabot-search huggingface dataset:
Growth control of human ovarian cancer cells by the dynein light chain and TGFβ receptor interacting protein km23-1
Authors: Kathleen M. Mulder, Nageswara Rao Pulipati, Xin Liu, Baodong Sun, Yan Zhao, Qunyan Jin, Wei Ding, Manoj K. Pandey, Jonathan P. Huber
Journal: Clinical Cancer Research (2010)

Abstract We have identified km23-1 as a TGFβ signaling intermediate that is also a light chain of the minus-end directed motor protein dynein (DLC). Our results suggest that km23-1 (also termed DYNLRB1/robl1/mLC7-1/Dnlc2a) can function as a “motor receptor” to recruit TGFβ signaling components to the dynein motor for endosomal trafficking prior to nuclear translocation. For example, we have shown that overexpression of the dynactin subunit dynamitin, which is known to disrupt dynein-mediated intracellular transport, blocks TGFβ-stimulated nuclear translocation of Smad2. Further, siRNA blockade of km23-1 resulted in a reduction both in nuclear levels of phosphorylated (ie, activated) Smad2 and of TGFβ/Smad2-dependent transcriptional activity (JBC 282: 19122, 2007). Similarly, we have shown that km23-2 is required for Smad3 TGFβ signaling (JCP 221: 707, 2009). However, many human ovarian cancer cells (HOCCs) have lost growth inhibitory responsiveness to TGFβ. In order to assess whether km23-1 could also regulate the growth of aggressive, TGFβ-resistant HOCCs, we developed a tet-off-inducible model system for induction of wild-type km23-1 expression in SKOV-3 HOCCs. Here we show that overexpression of km23-1 (by 10-20 fold) suppressed the growth of the cells in vitro and markedly impeded tumor formation in vivo. Fluorescence-activated cell sorting (FACS) analysis in the SKOV-3 model system demonstrated an increased fraction of cells in G2/M after induction of km23-1 expression (dox removal), compared with controls. Similar results were obtained for the TGFβ-resistant IGROV-1 HOCCs. Additional studies revealed that km23-1 overexpression in HOCCs increased the mitotic index, in association with activation of both MEK and ERK and an elevation of cyclin B1 protein expression levels. The elevated levels of phospho-MEK, phospho-ERK, and cyclin B1, as well as the distribution of the cells in mitosis, suggest that the cells are delayed in prometaphase/ metaphase. This mitotic delay, followed by cell death, appears to be the mechanism by which high levels of km23-1 can suppress ovary tumor growth in vivo. Since dynein is known to have critical functions at this point in mitosis by inactivating the spindle assembly checkpoint (SAC), studies are underway to investigate how km23-1 overexpression regulates the SAC to cause the reduced tumor formation in vivo. This work was supported by NIH grants CA100239, CA92889, and CA90765 to KMM. Our results indicate that km23-1 is a critical ovarian cancer target for the development of novel diagnostic and therapeutic agents. In this regard, US patents have been issued to KMM related to km23-1-based methods for diagnostic/prognostic screening, as well as for the identification of km23-1-based therapeutic agents for ovarian cancer (US 7,229,758 B2; 6-07 &amp; US 7,741,043; 6-10).
Association of Contemporary Sensitive Troponin I Levels at Baseline and Change at 1 Year With Long-Term Coronary Events Following Myocardial Infarction or Unstable Angina
Authors: Harvey D. White, Andrew Tonkin, John Simes, Ralph Stewart, Kristy Mann, Peter Thompson, David Colquhoun, Malcolm West, Paul Nestel, David Sullivan, Anthony C. Keech, David Hunt, Stefan Blankenberg
Journal: Journal of the American College of Cardiology (2013)
Clinical, power Doppler sonography and histological assessment of the psoriatic plaque: short-term monitoring in patients treated with etanercept
Authors: M. Gutierrez, R. De Angelis, M.L. Bernardini, E. Filippucci, G. Goteri, G. Brandozzi, G. Lemme, A. Campanati, W. Grassi, A. Offidani
Journal: British Journal of Dermatology (2010)

To date, the diagnosis of psoriasis is based on both clinical history and physical examination, and its severity is assessed by the Psoriasis Area and Severity Index (PASI). Continuous technological advances in the field of sonography have led to the development of equipment with high power Doppler frequency, which allows for very detailed morphological information regarding the dermal blood flow.To compare power Doppler sonography (PDS) with clinical and histological findings before and after etanercept treatment in patients with psoriasis.Twelve patients with a clinical diagnosis of psoriasis were enrolled in this study. The PASI, PDS and histological examinations were assessed in all patients on the same day at baseline, and after 12 weeks of biological treatment. PDS examination was performed by an experienced sonographer, using a sonographic system equipped with transducer ranging from 6 to 18 MHz and Doppler frequency ranging from 7 to 14 MHz.At follow up there was a significant decrease in PASI. A significant change was also detected for the PDS findings (P = 0·005). At baseline the median value for factor VIII staining was 1·5, and the median value for vascular endothelial growth factor (VEGF) staining was also 1·5. At follow up there was a significant decrease in both factor VIII and VEGF staining scores. Moreover, a positive correlation between reduction in PDS score and improvement in clinical and histological scores was found: Spearman's ρ = 0·639, P = 0·0022; Spearman's ρ = 0·619, P = 0·0013; Spearman's ρ = 0·765, P = 0·0002, respectively.Our results show a significant correlation between PDS findings and both PASI and histological degree of vascularization before and after etanercept treatment. These data provide evidence in favour of the validity of PDS in the assessment of dermal perfusional changes in patients with psoriatic plaques.
655. Compacted DNA Nanoparticles Effectively Transfect Brain Cells In Vitro and In Vivo
Authors: David M. Yurek, Anita Fletcher-Turner, Mark J. Cooper
Journal: Molecular Therapy (2005)

This study determined the feasibility of using DNA compacted into unimolecular nanoparticles as a gene therapy delivery system for post-mitotic brain cells. DNA compacted with polyethylene glycol (PEG)-substituted 30-mer lysine peptides has been shown to effectively transfect multiple types of non-dividing cells and tissues, including growth-arrested neuroblastoma cells, and may be a viable system for the delivery of neurotrophic factors, such as glial cell line-derived neurotrophic factor (GDNF), to dopaminergic neurons. This formulation of DNA nanoparticles is non-inflammatory and non-immunogenic in peripheral organs, and therefore may circumvent the problem of immunogenicity that is inherent with some viral vectors. In this study we examined whether specific nanoparticle formulations of single DNA molecules encoding enhanced green fluorescent protein (EGFP) are capable of transfecting brain cells in primary ventral midbrain cultures or after direct injection into the rat striatum. Ellipsoidal and rod-like formulations of DNA nanoparticles were prepared by using lysine peptides having either trifluoroacetate (TFA) or acetate, respectively, as the polycation counterion at the time of DNA mixing. Primary ventral midbrain cultures were maintained for 5 days. During the first 4 days, cultures were exposed to DNA compacted into the acetate rod nanoparticles [250 ng/well; 5.0 |[times]| 1010 particles]; fresh media containing nanoparticles was added to the cultures on a daily basis. On the fifth day in vitro (DIV 5), |[sim]|99% of the cells expressing either the neural marker NeuN or the glial marker glial fibrillary acidic protein (GFAP) were also EGFP+; similarly, most tyrosine hydroxylase-positive cells also co-expressed EGFP. In a second study, ellipsoidal and rod-like nanoparticles were injected directly into the striatum of young adult rats and 4-5 days later we observed EGFP expression in |[sim]|50% of both neurons and glia located in the brain tissue surrounding the injection site. There was no evidence of an inflammatory cell infiltrate at the injection site. In conclusion, the results from these in vitro and in vivo studies suggest that compacted DNA nanoparticles can be used as a non-viral gene therapy technique to efficiently transfect post-mitotic brain cells and induce transgene expression in both neurons and glia. This study was supported by NS42862 (NINDS/NIH) and DAMD 17-01-1-0786 (DOD).
TRICHINOSIS: A SPORADIC OUTBREAK WITH REPORT OF A CASE
Authors: James S. Sweeney, Frank B. Queen, Thomas F. Barrett
Journal: Annals of Internal Medicine (1944)

Case Reports1 December 1944TRICHINOSIS: A SPORADIC OUTBREAK WITH REPORT OF A CASEJAMES S. SWEENEY, Col., MC, F.A.C.P., FRANK B. QUEEN, Lt. Col., MC, THOMAS F. BARRETT, Capt., MCJAMES S. SWEENEY, Col., MC, F.A.C.P.Search for more papers by this author, FRANK B. QUEEN, Lt. Col., MCSearch for more papers by this author, THOMAS F. BARRETT, Capt., MCSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-21-6-1037 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTrichinosis is a disease about which little is written at the present time, partly because it is infrequently diagnosed. We are inclined, as are others, to suspect that chronic trichinosis is much more prevalent in this country than might be indicated by the literature and statistics.The purpose of this paper is to draw attention to this condition and to report a case observed in this hospital. The patient was one of many victims of a very severe outbreak which led to an unusually interesting epidemiologic study.CASE REPORTOur patient, aged 32, was inducted into the Army September 5,... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication November 13, 1943.Bushnell General Hospital PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byTrichinosis A Point Source OutbreakDONALD G. POCOCK, M.D., F.A.C.P., PAUL R. SCHNURRENBERGER, D.V.M., ARTHUR D. ZIEGLER, M.P.H., FREDERICK H. WENTWORTH, M.D., WINSLOW J. BASHE JR., M.D. 1 December 1944Volume 21, Issue 6Page: 1037-1041KeywordsEpidemiology Issue Published: 1 December 1944 PDF downloadLoading ...
Abstract 72: Addition of Real-Time CPR Feedback Improves Immediate Outcomes for Out-of-Hospital Cardiac Arrest
Authors: John Freese, Mark Menegus, Jeffrey Rabrich, Todd Slesinger, Robert Silverman, Norma Keller, Judy Dillworth, Doug Isaacs, David Ben-Eli, Pamela Lai, Glenn Asaeda, David Prezant
Journal: Circulation (2014)

Introduction: The 2010 American Heart Association Guidelines stated that “cardiopulmonary resuscitation prompt and feedback devices may be useful for training rescuers and may be useful as part of an overall strategy to improve the quality of CPR for actual cardiac arrests.” We sought to assess the effect of one such device on OOHCA outcomes in a large, urban setting. Methodology: Out-of-hospital cardiac arrest data from two consecutive twelve-month periods was analyzed: August 1, 2010 - July 31, 2011 (control) and August 1, 2011 - July 31, 2012 (CPR feedback). During the CPR feedback period, defibrillators capable of providing real-time audible and visual CPR feedback were added to standard prehospital resuscitation care. Results: There were 850 and 748 bystander witnessed arrests of cardiac etiology in the two periods. Patient and arrest characteristics for the two groups did not differ with respect to age, gender, race, response time, bystander witnessed status, or the frequency of bystander CPR. As compared to the control period, the addition of real-time CPR feedback resulted in a significant improvement in immediate outcomes: return of spontaneous circulation, or ROSC (39.59% vs. 47.71%, p=0.001); sustained ROSC (31.17% vs. 36.14%, p= 0.037). However, there was no improvement in survival to hospital admission (24.88% vs. 25.32%, p=0.85) or survival to hospital discharge (5.63% vs. 6.72%, p=0.43). In addition, among those survivors for whom neurologic status is known, the addition of CPR feedback did not significantly change the proportion of survivors considered neurologically intact (70.37% vs 65.63%, all p=0.78). Conclusions: The addition of real-time CPR feedback to a large urban EMS system’s resuscitation care resulted in significant improvements in immediate survival but did not affect overall survival rates. It is also possible earlier introduction of these devices (through their use by first responder and/or earlier arriving basic life support units) may provide greater benefit. Further data analysis is required to determine the specific effect of CPR feedback devices on long-term survival and to optimize their use in resuscitation care.
Abstract MP93: Impact of Reducing Sedentary Time on Vascular Endothelial Function in Previously Sedentary Older Adults
Authors: Tisha M Suboc, Daniel Knabel, Scott J Strath, Mobin Malik, Allison Couillard, Michael Widlansky
Journal: Circulation (2014)

Background: We have previously reported that increasing habitual moderate intensity (3-6 METs) physical activity (PA) reverses aging-associated vascular endothelial dysfunction, a surrogate marker of cardiovascular risk, in previously sedentary adults ≥ 50 years old. However, whether this relationship is in part related to a reduction in sedentary time concomitant with increased PA is unknown. Methods: A post hoc analysis on data from 96 sedentary adults ages ≥ 50 years (average age 62±7 years) who participated in a randomized control trial evaluating the impact of a 12 week intervention to increase PA was performed. The intervention aimed to increase moderate intensity PA using pedometer guidance with or without the aid of an interactive website which taught participants how to integrate PA into their daily routine. Amount and intensity of PA were measured pre- and post-intervention by accelerometer. Subjects were divided into tertiles of based on change in percent of sedentary activity (&lt; 1. 5METs) over the study period: (1) 5% or greater reduction in sedentary time, (2) 0-4.99% reduction, and (3) increase in sedentary time. Vascular endothelial function was measured by brachial artery flow mediated dilation (FMD%) prior to and at the end of a 12 week intervention period. Data were analyzed by two-way mixed ANOVA with post hoc testing as appropriate. Results: Sedentary time decreased in the study population (P=0.001), driven by a 101 minute drop in sedentary time in group 1 (N=27, 653±121 to 552±100 min, P &lt; 0.001), a 42 minute drop in group 2 (N=29, 699±92 to 657±70 min P=0.003), and a 44 minute increase in group 3 (N=40, 629±93 to 673±120 min, P =0.02). While FMD% increased in the entire study population (P=0.008), this increase was not influences by differences in the change in sedentary time (P=0.73, group 1: 5.4±2.9 to 7.0±3.6%, group 2: 5.7±2.9 to 6.9±4.3%, group 3: 6.0±2.5 to 6.7±3.6%). No differences in endothelium-independent vasodilation were seen. Using equal tertiles for change in sedentary time or higher thresholds for reductions in sedentary time (7.5% or 10%) for group 1 did not alter these results. Conclusion: Increasing moderate intensity PA improves endothelial function in adults ≥ 50 years but this improvement is not associated with the reduction in the amount of sedentary time. Greater than a 10% reduction in the amount of sedentary time may be necessary to see its favorable impact on the vascular endothelium.
The nature of the antigen in induced resistance to tumors
Authors: Morris K. Barrett, Walter H. Hansen, Bernard F. Spilman
Journal: Cancer Research (1951)

Summary  With mice of strains DBA and C and a sarcoma which arose in strain DBA but is transplantable to both strains, resistance to implantation of the tumor was induced (in strain C) by the prior inoculation of defibrinated blood or fractions thereof. The objective was to confirm and extend previous work and to discover some of the essential attributes of the antigen involved.  It was confirmed that resistance can be elicited by such methods when the host is of a different strain than the tumor but not when the host and tumor are of the same strain.  It was shown that this sarcoma is susceptible to this type of immunity.  The effective antigen was found in the cells and not in the serum, and it was noted further that a relatively pure suspension of washed red cells was an efficient antigen.  The degree of resistance induced was proportionate to the dose of antigen given, both in the case of defibrinated blood and of washed red cells. The minimal dose which can produce a significant degree of resistance was found to be as little as or less than 0.0031 cc. of defibrinated blood or its equivalent in red cells.  The power of a suspension of red cells to elicit resistance was destroyed when the cells were laked by either slow freezing, suspending in distilled water momentarily, or brief exposure to the vibrations of high-pitched audible sound.  The interpretation adopted, tentatively, is that the antigenicity involved is based in some way upon the architectural integrity of the cell, its surface, or a major fraction thereof.
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial
Authors: G Kees Hovingh, John J P Kastelein, Sander J H van Deventer, Patrick Round, John Ford, Danish Saleheen, Daniel J Rader, H Bryan Brewer, Philip J Barter
Journal: The Lancet (2015)
Abstract 14: Poor Physical Activity is Associated with Subclinical Myocardial Injury in Obese Adults
Authors: Roberta Florido, Chiadi E Ndumele, Yuanjie Pang, Kunihiro Matsushita, Jennifer A Schrack, Mariana Lazo, Vijay Nambi, Roger S Blumenthal, Aaron R Folsom, Josef Coresh, Christie M Ballantyne, Elizabeth Selvin
Journal: Circulation (2015)

Background: Obesity is associated with myocardial injury and subsequent heart failure (HF). Higher physical activity (PA) is associated with reduced risk of HF among individuals with obesity, but the mechanisms for this protective association remain poorly understood.

Hypothesis: We hypothesized that low levels of PA would be independently associated with a higher prevalence of subclinical myocardial injury among obese individuals, as assessed by a high-sensitivity assay for cardiac troponin T (hs-cTnT).

Methods: We evaluated 9,845 ARIC participants without cardiovascular disease at Visit 4 (1996-99) and with body-mass index (BMI) >18.5 kg/m2. PA was assessed at Visit 3 (1993-95) using a modified Baecke questionnaire. The sports indices were converted into minutes per week of moderate or vigorous exercise, and categorized as per AHA guidelines as: recommended (≥150 min/wk of moderate + vigorous intensity or ≥75 min/wk of vigorous intensity); intermediate (1-149 min/wk of moderate + vigorous intensity or 1-74 min/wk of vigorous intensity); or poor (0 min/wk of moderate or vigorous exercise). BMI was also assessed at Visit 3. The primary outcome was elevated hs-cTnT (>14 ng/L) measured at Visit 4. We constructed multivariable logistic regression models to assess the association of PA and obesity with elevated hs-cTnT.

Results: After multivariable regression, relative to recommended PA, poor PA was associated with elevated hs-cTnT (OR 1.33, 95% CI: 1.09-1.61). In analyses stratified by obesity status, lower PA levels were associated with subclinical myocardial injury among non-obese and obese participants (p for trend <0.02 in both groups). Among obese participants, those with recommended PA levels had the lowest likelihood of myocardial injury (Table).

Conclusion: Low PA was associated with prevalent subclinical chronic myocardial injury as manifested by elevated hs-cTnT. This may help explain the possible protection conferred by PA against the development of HF in obese individuals.

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Emergence of a novel GII.17 norovirus – End of the GII.4 era?
Authors: M de Graaf, J van Beek, H Vennema, A T Podkolzin, J Hewitt, F Bucardo, K Templeton, J Mans, J Nordgren, G Reuter, M Lynch, L D Rasmussen, N Iritani, M C Chan, V Martella, K Ambert-Balay, J Vinjé, P A White, M P Koopmans
Journal: Eurosurveillance (2015)

In the winter of 2014/15 a novel GII.P17-GII.17 norovirus strain (GII.17 Kawasaki 2014) emerged, as a major cause of gastroenteritis outbreaks in China and Japan. Since their emergence these novel GII.P17-GII.17 viruses have replaced the previously dominant GII.4 genotype Sydney 2012 variant in some areas in Asia but were only detected in a limited number of cases on other continents. This perspective provides an overview of the available information on GII.17 viruses in order to gain insight in the viral and host characteristics of this norovirus genotype. We further discuss the emergence of this novel GII.P17-GII.17 norovirus in context of current knowledge on the epidemiology of noroviruses. It remains to be seen if the currently dominant norovirus strain GII.4 Sydney 2012 will be replaced in other parts of the world. Nevertheless, the public health community and surveillance systems need to be prepared in case of a potential increase of norovirus activity in the next seasons caused by this novel GII.P17-GII.17 norovirus.
The expression of ΔNp63 and ΔNp73 as early markers in cervical carcinoma
Authors: Inthira Tussakhon, Temduang Limpaiboon, Chanvit Leelayuwat, Pissamai Yuenyao, Anucha Puapairoj, Patcharee Jearanaikoon
Journal: Clinical Cancer Research (2007)

C71    Abstract  Cervical cancer (CXCA) is a major cause of cancer death among women worldwide. It is well established that viral oncoprotein E6 and E7 from high risk HPV is a necessary cause of cervical cancer development by interfering apoptosis and cell cycle via p53 and pRb inactivation. Both p63 and p73 share significant homology in structure and function to p53; however, p63 and p73 can encode truncated N-terminal isoforms (ΔNp63 and ΔNp73) which can inhibit transactivating function of full length isoforms (TAp63 and TAp73). In this study, we attempt to investigate the correlation between overexpression of ΔNp63 and ΔNp73 in cervical dysplasia (n=98) and invasive cervical cancer (n=98) compared to normal cervix (n=54), using immunohisochemistry (IHC) technique. Our data demonstrated significant association between the expression of ΔNp63 and ΔNp73 in both cervical dysplasia ( P  P  2 ) test. Additionally, the expression of ΔNp63 and ΔNp73 was further analyzed between low grade squamous intra-epithelials lesion (LSIL) and high grade squamous intra-epithelials lesion (HSIL) compared to normal cervix. Association was significantly found between LSIL and normal cervix ( P
Clinical Cardiac Electrophysiology: Techniques and Interpretations.
Authors: Mark E. Josephson
Journal: Annals of Internal Medicine (1980)

Historical perspectives electrophysiologic investigation sinus node function atrioventricular conduction intraventricular conduction disturbances miscellaneous phenomena related to atrioventricular conduction ectopic rhythms and premature depolarizations supraventricular tachycardias atrial flutter and fibrilation pre-excitation syndromes recurrent ventricular tachycardia myocardial infarction - special considerations evaluation of therapeutic modalities - antiarrhthymic agents, pacing and defibrilation, surgical and non-surgical ablation.
In vitro activity of telithromycin (HMR 3647) against Greek Streptococcus pyogenes and Streptococcus pneumoniae clinical isolates with different macrolide susceptibilities
Authors: S. Ioannidou, P.T. Tassios, L. Zachariadou, Z. Salem, M. Kanelopoulou, S. Kanavaki, G. Chronopoulou, N. Petropoulou, M. Foustoukou, A. Pangalis, E. Trikka-Graphakos, E. Papafraggas, A.C. Vatopoulos
Journal: Clinical Microbiology and Infection (2003)