tbuckley/cabot-search huggingface dataset:
Abstract 21468: A Novel CaMKII/ERK Interaction n the Heart Sustains Cardiac Hypertrophy in Spontaneously Hypertensive Rats
Authors: Ersilia Cipolleta, Gaetano Santulli, Maria Rosaria Rusciano, Antonio Anastasio, Angela Serena Maione, Carmine del Giudice, Pietro Campiglia, Maddalena Illario, Guido Iaccarino
Journal: Circulation (2010)

The molecular mechanism underlying Cardiac hypertrophy involves, among others, abnormal intracellular Ca++ dynamics. Ca++/Calmodulin protein kinase II (CaMKII) activation mediates Ca++ signaling in the hypertrophic transduction pathways. Nevertheless, the mechanism by which CaMKII integrates with other pathways is incompletely understood. We showed that phenylephrine (PE) induces cell proliferation through CaMKII and ERK complex formation, promoting phosphorylation and nuclear localization of both proteins. We hypothesize that the association with ERK, promotes nuclear localization in hypertrophic cardiomyocytes. In H9C2 cardiomyoblasts, PE induces both ERK and CaMKII activation and interaction which can both be reduced by the non selective CaMKs inhibitor KN93, by the selective CaMKII inhibitor AntCaNtide, and by the MEK/ERK inhibitor UO126. Next, we found that PE induces a time-dependent accumulation of both ERK and CaMKII into the nucleus, prevented by AnTCaNtide and UO126 pretreatment, supporting the ...
Suicide Attempts in the US Army During the Wars in Afghanistan and Iraq, 2004 to 2009
Authors: Robert J. Ursano, Ronald C. Kessler, Murray B. Stein, James A. Naifeh, Pablo A. Aliaga, Carol S. Fullerton, Nancy A. Sampson, Tzu-Cheg Kao, Lisa J. Colpe, Michael Schoenbaum, Kenneth L. Cox, Steven G. Heeringa
Journal: JAMA Psychiatry (2015)

The rate of suicide attempts in the US Army increased sharply during the wars in Afghanistan and Iraq. Research on this important health outcome has been hampered by the lack of integration among Army administrative data systems.
Therapeutic Arteriogenesis Has Arrived
Authors: Wolfgang Schaper
Journal: Circulation (2001)

he report by Seiler et al 1 on a clinical trial using granulocyte-macrophage colony-stimulating factor (GM-CSF) to stimulate the growth of coronary collateral vessels is the temporary culminating point of a long history of research that started in the early 1940s with the observation that the pressure measured in the distal stump of an occluded canine coronary (or femoral or carotid) artery rose as a function of time and was caused by the development of a collateral circulation. 2,3Strandness 4 and Schoop and Jahn 5 were probably the first to measure the pressure in the distal stump of a peripheral artery in the leg of patients for an estimation of residual perfusion.
Identification of critical formulation and processing variables for metoprolol tartrate extended-release (ER) matrix tablets1This manuscript represents the personal opinions of the authors and does not necessarily represent the views or policies of the FDA.1
Authors: Gurvinder Singh Rekhi, Ranjani V Nellore, Ajaz S Hussain, Lloyd G Tillman, Henry J Malinowski, Larry L Augsburger
Journal: Journal of Controlled Release (1999)
986. Efficient Gene Delivery to Human and Rodent Islets with Double Stranded (ds)-AAV2-Based Vectors
Authors: Khaja K. Rehman, Zhong Wang, Rita Bottino, A. N. Balamurugan, Juan Li, Xiao Xiao, Massimo Trucco, Paul D. Robbins
Journal: Molecular Therapy (2004)

Top of pageAbstract
Islet transplantation represents a potential cure for Type 1 diabetes mellitus. However, the survival of allogeneic islets following transplant, especially in an autoimmune background is extremely poor. The transfer of immunomodulatory and anti-apoptotic genes into islet cells can improve islet function and survival post-transplant. Several different viral vectors have been used to infect intact rodent and human islets. The immunogenecity, and transient gene expression of adenoviral vectors and the high multiplicity of infection of adeno-associated viral vectors required for infection have limited their use in clinical human islet transplantation. We have compared the ability of ds-AAV2 and ss-AAV2 viral vectors to transfer green fluorescent protein gene into intact human and murine islets. We demonstrate that ds-AAV-2 efficiently transduced both human and murine islets at lower MOI as compared to ss-AAV without impairing islet viability and insulin secretion capacity of b-cells both in vitro and in vivo following transplantation. Moreover, islets transduced with dsAAV express GFP up to six months in syngeneic islet grafts without eliciting immune response. In conclusion, these results demonstrate dsAAV viral vectors are non-toxic, transduce islet cells efficiently and can be used as tool to deliver therapeutic genes in to islet cells to facilitate future clinical islet transplantation.
Cellular composition of bronchoalveolar lavage (BAL) as inflammation indicator in patients with chronic obstructive pulmonary disease (COPD)
Authors: Vukoica Karlicic
Journal: European Respiratory Journal (2014)

INTRODUCTION:COPD is characterized by constant and progressive airflow restriction due to chronic inflammation in the airways of the lung caused by harmful gases and particles. Comorbidity in COPD is a consequence of systemic inflammation, or occurs as a result of spreading inflammatory processes from lung to systemic circulation.  AIM: Estimate the possibility to determine the inflammation level in the lungs and the importance of inhaled corticosteroids with/without long acting beta agonist in treatment of patients with COPD, based on cell analyses of bronchoalveolar lavage (BAL).  METHOD AND PATIENTS:In 58 patients, COPD was diagnosed; 18 patients in I GOLD stage, 16 in II GOLD stage, 12 in III GOLD stage and 8 patients in IV GOLD stage. All patients underwent functional diagnostic of the lung, MSCT, video bronchoscopy with BAL and cytological analysis of BAL.  RESULTS: I GOLD stage, 19,8% lymphocytes in BAL and 26,9% neutrophils.II GOLD stage,21,2% lymphocytes in BAL and 41% neutrophils.III GOLD stage,9,1% lymphocytes in BAL and 55,2% neutrophils.IV GOLD stage 4,4% lymphocytes in BAL 78,1% neutrophils.  CONCLUSION:Lymphocytes are inversely proportional, and leucocytes are directly proportional to COPD stage. There is larger number of lymphocytes in I and II GOLD stage, while neutrophils number increases from I to IV GOLD stage.As neutrophils in BAL rise, lung function decreases.
No Survival Advantage
Authors: Rebecca Voelker
Journal: JAMA (1998)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
CD Rom: Current Medical Diagnosis and Treatment 1998
Authors: F. Sullivan
Journal: BMJ (1999)

Stephen J McPhee, Lawrence M Tierney Jr, Maxine A Papadakis, Ralph Gonzales Appleton and Lange, £67 ISBN 0 8385 1480 4 Rating: ![Graphic][1]</img>![Graphic][2]</img>![Graphic][3]</img> Can a reference source really meet the needs of “a student, resident or clinician,” as the user's guide for this CD claims? To do so, the information it provides would need to be readily accessible, up to date, and capable of answering the questions … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif [3]: /embed/inline-graphic-3.gif
Abstract 9761: Novel Modulators of Low Density Lipoprotein Receptor Metabolism
Authors: Nabil Elshourbagy, Harold Meyers, Caitlin Medve, Shaker Mousa, Sherin Abdel-Meguid
Journal: Circulation (2014)

Intervention with drugs to reduce Low Density Lipoprotein-cholesterol (LDL-C) has proven to decrease the risk of subsequent cardiovascular events, including mortality. Our goal is to develop novel, small molecule, LDL-C lowering drugs by targeting the Low Density Lipoprotein Receptor (LDLR) degradation pathway, which is modulated by the protease proprotein convertase subtilisin-like kexin type 9 (PCSK9). PCSK9 has been shown to bind to the epidermal growth factor-like repeat A (EGF-A) domain of the LDLR; it enhances the degradation of the LDLR by an unknown. We successfully integrated virtual screening methods and cell based assays into a simple, efficient procedure and identified compounds that interfere with the PCSK9-LDLR interaction. Using the atomic coordinates of the crystal structure of the PCSK9/LDLR-EGF-A complex, about a million drug-like compounds were docked in silico into the region of PCSK9 where LDLR-EGF-A binds. We selected 179 top scoring compounds that showed the best fit in the binding site as well as the greatest number of interactions with PCSK9. These compounds were tested in (a) our PCSK9/LDLR dependent HEK293 cell-based recombinant assay and (b) the endogenously expressed LDLR in HepG2/PCSK9 dependent cell based assay for their ability to upregulate the LDLR. From these screening campaigns, eleven compounds consistently exhibited concentration dependent increase in the LDLR as comparable to control, with IC 50 s in the low micromolar range. Three of the top picks were shown to exhibit a 5 to 10 fold up-regulation at 1.6 μM in two cell lines. In addition, these compounds also exhibited an increase in the fluorescently labeled DiI-LDL uptake in the nanomolar range in situ . Furthermore, in a two week animal study, subcutaneous injection of 4 mg/kg of one of these compounds resulted in a 32% reduction of the total cholesterol level in mice fed a high fat/high cholesterol diet as compared to 27% cholesterol reduction obtained with 40 mg/kg Atorvastatin. To our knowledge, no small molecule antagonist against PCSK9 has been reported, only mAbs. Thus, identifying such an oral small molecule PCSK9 inhibitor represents a tremendous advance and opportunity for drug development.
Self reporting of symptoms and delays in patients presenting to a rapid access lung cancer clinic (RALCC)
Authors: Mateen Uzbeck, Colm Geraghty, Eleanor Dunican, Seamus Linnane, Ross Morgan
Journal: European Respiratory Journal (2011)

Introduction: The RALCC at our hospital is aimed at expediting the diagnosis of suspected thoracic malignancies.

Methods: A self-reported questionnaire to consecutive patients on their first visit. Patient's perception of why they were attending, symptoms, duration before seeking medical attention, time to referral and risks for lung cancer recorded.

Results: 154 patients, 81 male, 73 female, mean age 63 years (21-86). GP's made most referrals 87% and 68% perceived abnormal radiology as reason for attendance. Majority were symptomatic 88.6% with 57% reporting ≥3 symptoms. Cough was most common presenting symptom 61%, fatigue 52%, dyspnoea 45%, chest infection 45%, chest pain 40%, weight loss 32% and haemoptysis 25%. Haemoptysis had the least delay in presenting to a health care provider (mean 30 days, range 2-120) whereas for cough, dyspnoea and chest pain mean dealy was 4.5 months. Average delay in seeking medical attention and referral to RALLC was 14 weeks. 72% were current or ex-smokers and 21% reported at least one first degree relative with lung cancer.

Conclusions: s ignificant delays exist between symptom onset and presentation to a health care provider and depends on symptom type. The bulk of the delay was before patients sought medical attention but there was still a sizeable delay between presentation and referral toRALCC. One in 5 patients had a first degree relative with lung cancer indicating that this may have been a factor in the decision to refer. Our study highlights the need for increased public awareness regarding the presenting symptoms of lung cancer and there exists the opportunity to reduce delays in diagnosis resulting in better outcomes.
Mental disorders and comorbidity in suicide
Authors: M M Henriksson, H M Aro, M J Marttunen, M E Heikkinen, E T Isometsä, K I Kuoppasalmi, J K Lönnqvist
Journal: American Journal of Psychiatry (1993)

The purpose of this study was to investigate the prevalence and comorbidity of current mental disorders defined by DSM-III-R among a random sample of suicide victims from a nationwide suicide population.Using a psychological autopsy method, the authors collected comprehensive data on all suicide victims in Finland during 1 year. Retrospective axis I-III consensus diagnoses were assigned to 229 (172 male, 57 female) victims.One or more diagnoses on axis I were made for 93% of the victims. The most prevalent disorders were depressive disorders (59%) and alcohol dependence or abuse (43%). The prevalence of major depression was higher among females (46%) than among males (26%). Alcohol dependence was more common among the males (39% versus 18% for females). A diagnosis on axis II was made for 31% and at least one diagnosis on axis III for 46% of the cases. Only 12% of the victims received one axis I diagnosis without any comorbidity.The majority of suicide victims suffered from comorbid mental disorders. Comorbidity needs to be taken into account when analyzing the relationship between suicide and mental disorders and in planning treatment strategies for suicide prevention in clinical practice.
593. Recombinant Measles Viruses Encoding Suicide Genes for Oncolytic Therapy
Authors: Christoph Springfeld, von Messling Veronika, Frenzke Marie, Cattaneo Roberto
Journal: Molecular Therapy (2004)

Infection with wild-type measles virus (MV), a negative-stranded RNA virus of the family Paramyxoviridae, has been associated with spontaneous remissions in some patients with Hodgkins lymphoma and leukemia. Subsequent studies in vitro and in mouse models of lymphoma, myeloma, glioma, and ovarian cancer with an attenuated MV strain of the Edmonston lineage (MV-Edm) have demonstrated a strong oncolytic effect. However, in these mouse models, the implanted tumors could not always be eradicated by the treatment with MV-Edm. Therefore, MV with enhanced and inducible oncolytic properties are highly desirable.
Abstract 4295: A 3D culture model for screening of cancer therapeutics
Authors: Kalpana Patel, Belinda O'Clair, Tim O'Callaghan, Daniel M. Appledorn, Derek Trezise
Journal: Cancer Research (2014)

Abstract 3D cell culture models are currently of great interest to the bioscience community. This is most notable in the cancer biology area, where a growing body of evidence suggests that more relevant and translational observations can be made by testing compounds in a physiological relevant 3D model compared to a 2D model. In this study, we take a kinetic, live-cell imaging approach to measure the growth or shrinkage of non-adherent tumor spheroids using Ultra Low Attachment (ULA) 96-well and 384-well microtiter plates (Corning®). These round-bottomed, hydrogel coated plates facilitate the formation of spheroids by promoting self-adherence as opposed to adherence to the plate surface. In a single cell type, monoculture model, A549 lung epithelial carcinoma cells developed into single spheroid structures in each well of 96 and 384-well plates within 48-96 hours in culture. In both plate types, the resulting spheroid size, ranging from 330 µm - 600 µm, was proportional to the number of cells (1K - 5K cells per well). Post formation, spheroids remained untreated or were subjected to three test agents, staurosporine, oxaliplatin or cycloheximide. The increase or decrease in spheroid size was monitored over 3 - 10 days using the IncuCyte™ ZOOM Live Content Imaging system. Using the red fluorescent channel, spheroid growth was analyzed using fluorescent area and intensity metrics. Whereas staurosporine and oxaliplatin significantly decreased spheroid size at high concentrations, cycloheximide treatment resulted in a cytostatic response, effectively inhibiting spheroid growth in a concentration dependent manner, while not reducing total spheroid area at any tested concentration. Interestingly, in side-by-side comparisons of kinetic 2D and 3D assays, we observed a significant, 10-fold (one log) shift in the pharmacology of cycloheximide. In a 3D co-culture breast cancer model, this study also illustrates the effect of Lapatinib on SK-BR-3 cells grown in the presence of mammary derived stromal cells (fibroblasts). Together, this study describes a kinetic, live-cell approach to measuring spheroid size over time, illustrates a differential response of cycloheximide in a 3D system compared to identically treated cells grown in a 2D monolayer, and details a complex co-culture method for elucidating the effect of Lapatinib in a physiologically relevant 3D model of breast cancer. Citation Format: Kalpana Patel, Belinda O'Clair, Tim O'Callaghan, Daniel M. Appledorn, Derek Trezise. A 3D culture model for screening of cancer therapeutics. [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 4295. doi:10.1158/1538-7445.AM2014-4295
Guidelines for the standardization of bronchial provocation tests with allergens
Authors: G. Melillo, K. Aas, A. Cartier, R. J. Davies, M. Debelic, S. Dreborg, K. F. Kerrebijn, A. Lassen, J. Pinto Mendes, A. Rizzo, R. R. Rosenthal, S. Tateishi, R. Corsico
Journal: Allergy (1991)
Correction: Mutations in the protein tyrosine kinase gene, PTPN11, cause Noonan syndrome
Authors: M. Tartaglia, E.L. Mehler, R. Goldberg, G. Zampino, H.G. Brunner, H. Kremer, I. van der Burgt, A.H. Crosby, A. Ion, S. Jeffery, K. Kalidas, M.A. Patton, R.S. Kucherlapati, B. Gelb
Journal: Nature Genetics (2001)
Abstract IA29: PI3′ -kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAFV600E/PTENNull melanoma
Authors: Marian M. Deuker, Victoria Marsh-Durban, Wayne A. Phillips, Jillian M. Silva, Martin McMahon
Journal: Cancer Research (2015)

Abstract Phosphatidylinositide 3′ (PI3′)-lipid signaling promotes the growth of BRAF-mutated melanomas initiated by expression of oncogenic BRAFV600E. Elevation of PI3′-lipid signaling commonly occurs via silencing of the PTEN tumor suppressor, which encodes a PI3′-lipid phosphatase. However mutational activation of PIK3CA, encoding the p110α catalytic subunit of PI3′-kinase (PI3K), or alterations in the PI3′-lipid effectors AKT1-3 have also been observed, albeit infrequently. To characterize the PI3K catalytic isoform dependency of BRAF-mutated melanoma, we utilized a panel of pharmacological isoform-selective PI3K inhibitors in conjunction with melanoma-derived cell lines and genetically engineered mouse (GEM) models of BRAF-mutated melanoma. While BRAFV600E/PIK3CAH1047R mutated melanoma was sensitive to p110α selective blockade, inhibition of BRAFV600E/PTENNull melanoma cell proliferation required combined blockade of p110α, p110δ and p110γ isoforms, and was insensitive to p110β blockade. In GEM models of BRAF-mutated melanoma, PI3K pathway inhibition elicited largely cytostatic effects, and significantly potentiated melanoma regression in response to BRAFV600E pathway-targeted inhibition. Interestingly, an inhibitor of p110α, δ and γ forestalled the onset of MEK inhibitor resistance in a GEM model of BRAFV600E/PTENNull melanoma. Thus, although single agent PI3K inhibition failed to elicit dramatic regression of BRAFV600E expressing melanomas, PI3K inhibitors may be useful in extending the duration of response to BRAFV600E pathway-targeted therapy. Citation Format: Marian M. Deuker, Victoria Marsh-Durban, Wayne A. Phillips, Jillian M. Silva, Martin McMahon. PI3′ -kinase inhibition forestalls the onset of MEK1/2 inhibitor resistance in BRAFV600E/PTENNull melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA29.
566. Inactivation of a Bacterial Quorum-Sensing Signal by Expression of Bacterial Autoinducer Inhibitor, aiiA, in Mammalian Cells
Authors: Egon A. Ozer, Joseph Zabner
Journal: Molecular Therapy (2004)

Many bacteria regulate production of extracellular virulence factors and biofilm formation through the cell-cell communication system, quorum-sensing. Quorum-sensing molecules frequently take the form of acylated homoserine lactones (HSLs). A gene recently isolated from Bacillus sp. 240B1 encodes an enzyme, AiiA, that inactivates HSLs through cleavage of the lactone ring. We asked whether expression of aiiA in mammalian cells would be sufficient to inactivate bacterial quorum-sensing signals in the cells' environment. The aiiA gene was cloned into a mammalian expression vector under the control of the CMV promoter. This construct was transfected into HeLa cells and allowed to express for 18 hours. Full-length transcripts of the gene were detected by RT-PCR in HeLa cells transfected with the aiiA vector, but were not detected in cells transfected with a GFP control vector. Recombinant AiiA activity was found in HeLa cell lysates and cell medium by means of a homoserine lactone bioassay. This bioassay employs a strain of E. coli producing β-galactosidase in response to HSL concentration. The level of HSL in the medium correlates linearly to β-galactosidase expression as assessed by the Galacton assay. We found that cell medium from aiiA-transfected HeLa cells incubated for five hours with 1μM butyryl-HSL (C4-HSL) showed a 20% reduction in HSL levels when compared to medium from control transfected cells and a 30% reduction in HSL levels when compared to medium from untransfected cells. Similarly, aiiA-transfected HeLa cell lysates were found to decrease HSL levels by 20% when compared to both control-transfected and untransfected HeLa cell lysates. Our findings represent the first report of aiiA transcription and function in mammalian cells. Based on these results, recombinant expression of aiiA in vivo may be a novel therapeutic intervention to prevent bacterial biofilm infections in the lungs of cystic fibrosis patients, in the bone in cases of osteomyelitis, or other tissues.
Gender and Primary Percutaneous Coronary Intervention for ST-Segment Elevation Myocardial Infarction: Symptom to Treatment Delay in Women
Authors: Matthijs A Velders, Helen Boden, Barend L van der Hoeven, Su-San Liem, Jael Z Atary, Ernst E van der Wall, Sjoerd H Hofma, Adrianus J van Boven, Martin J Schalij
Journal: Circulation (2011)
A memorable patient: Misery versus pleasure
Authors: C. A Pierach
Journal: BMJ (2000)

Risks of mammographyIt has been calculated that for every two million women aged over 50 who have been screened by means of a single mammogram, one extra cancer a year after 10 years may be caused by the radiation delivered to the breast.Compared with an incidence of breast cancer that approaches 2000 in every million women aged 60, this risk is very small. Unnecessary biopsiesA proportion of women who undergo biopsy will be found not to have cancer, but in Britain the number of women undergoing a biopsy for benign disease is small.The proportion of benign biopsies performed in a screening programme should be monitored and compared with that in an unscreened group of women of the same age.Women who require biopsy are likely to be extremely anxious, but there is no evidence that this anxiety is sustained if the results are benign.