tbuckley/cabot-search huggingface dataset:
Abstract 600: Inhibition of G Protein-Coupled Receptor Kinase-3 (GRK3) Rescues Cardiac Dysfunction after Pressure Overload
Authors: Jørgen A Gravning, Thomas G von Lueder, Thor Edvardsen, Ole J How, Ellen Aasum, Mohammad S Ahmed, Leif E Vinge, Birthe V Mikkelsen, Terje S Larsen, Otto A Smiseth, Havard Attramadal
Journal: Circulation (2006)

Background: Previous studies of transgenic mice with cardiac-restricted inhibition of G protein-coupled receptor kinase-3 (GRK3) have disclosed phenotype consistent with α 1 - adrenergic receptor (α 1 -AR) hyperresponsiveness. As opposed to GRK2 (β-ARK1), an isoenzyme with selectivity for β-AR, the pathophysiologic role of GRK3 in heart failure has not been investigated. Accordingly, the functional role of GRK3 during evolving cardiac dysfunction after pressure overload was dissected in this study. Methods and results: GRK3ct transgenic mice (Tg-GRK3ct) with α-MHC promoter-driven expression of mini-gene encoding the carboxyl-terminal membrane targeting domain of GRK3 were employed. Inhibition of endogenous GRK3 was confirmed by enhanced α 1 -AR mediated activation of ERK 1/2 in cardiac myocytes from Tg-GRK3ct as compared to non-transgenic littermates controls (NLC). Tg-GRK3ct mice characteristically displayed myocardial hypercontractility despite unaltered cardiac mass, compared to NLC. Pressure overload was induced by abdominal aortic banding (AB) in weight matched male Tg-GRK3ct (GRK3ct-AB) and NLC (NLC-AB) mice and compared with sham-operated Tg-GRK3ct (GRK3ct-SH) and NLC (NLC-SH) mice. Echocardiography disclosed similar baseline cardiac dimensions among all groups. Eight and twelve weeks after AB significant increases of cardiac mass were found in AB mice compared to sham, but no differences between GRK3ct-AB and NLC-AB were discerned. Eight weeks after AB, analysis of electrically paced, ex vivo perfused hearts at increasing filling pressures revealed preserved end-diastolic and end-systolic pressure-volume (PV) relations in GRK3ct-AB (n=10), with substantially higher cardiac output and dP/dt max compared to NLC-AB (n=10). Twelve weeks after AB, simultaneous in vivo PV-analysis revealed elevated end-diastolic pressure (10.6±3.1 mmHg vs. 2.7±2.2, p&lt;0.05) and lower cardiac output (7379±738 μL/min vs. 9847±785, p&lt;0.05) in NLC-AB (n=11) compared to GRK3ct-AB (n=16). Consistently, myocardial mRNA level of B-type natriuretic peptide was substantially elevated in NLC-AB compared to GRK3ct-AB (p&lt;0.05). Conclusion: Inhibition of cardiac GRK3 in mice rescues cardiac dysfunction and heart failure after pressure overload.
Neutralization of Glucagon by Antiserum as a Tool in Glucagon Physiology
Authors: J. J. Holst, H. Galbo, E. A. Richter
Journal: Journal of Clinical Investigation (1978)

The method of producing experimental glucagon deficiency by administration of glucagon antiserum was evaluated in rats. A pool of antisera was prepared, the affinity of which exceeded that of the glucagon receptors of liver cell membranes, whereas the binding capacity of the volume used amounted to more than one-third of the total glucagon content in the rat pancreas. That rapid, extensive, and lasting neutralization of glucagon had taken place after antiserum treatment was indicated by the following findings: When examined more than 1 h after the injection and after 60 min of exercise-stimulated glucagon production, all rats had excess free antibodies in plasma. The concentration of free glucagon was lowered to one-third of the concentration in control rats; at 37°C plasma samples could bind 25% of additional 300 pmol/liter of glucagon in 10 s, and 69% in 120 s; the glycemic response to exogenous glucagon was abolished. Antiserum treatment, however, had no effect on blood glucose in rats fasted for 3 and 10 h, in chemically sympathectomized and adrenomedullectomized rats, and in 48-h-fasted, acutely adrenalectomized rats. The antiserum was found to contain 460 nmol/liter of antibody-bound glucagon, originating in the rabbit in which the antiserum was raised. However, antibody preparations from which the bound glucagon had been effectively removed were equally ineffective in lowering the basal blood glucose in rats, although in three-fourths of the rats the concentration of free glucagon was lowered beyond detection limit.
Association of a 4-Tiered Classification of LV Hypertrophy With Adverse CV Outcomes in the General Population
Authors: Sonia Garg, James A. de Lemos, Colby Ayers, Michel G. Khouri, Ambarish Pandey, Jarett D. Berry, Ronald M. Peshock, Mark H. Drazner
Journal: JACC. Cardiovascular imaging (2015)
Allogeneic mixed lymphocyte reactions during a second round of ontogeny: normal accessory cells did not restore defective interleukin- 2 (IL-2) synthesis in T cells but induced responsiveness to exogeneous IL-2
Authors: S Cayeux, S Meuer, A Pezzutto, M Korbling, R Haas, R Schulz, B Dorken
Journal: Blood (1989)
Abstract 13232: Reverse Atrial Electrical Remodeling Induced by Continuous Positive Airway Pressure in Patients with Severe Obstructive Sleep Apnea
Authors: Helen Pang, Damian P Redfearn, Christopher S Simpson, Kevin Michael, Effie J Pereira, Peter W Munt, Michael F Fitzpatrick, Adrian Baranchuk
Journal: Circulation (2011)

Background: Obstructive sleep apnea (OSA) has been associated with atrial enlargement in response to high arterial and pulmonary pressures and increased sympathetic tone. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA although its impact on atrial electrical remodeling has not been investigated. Signal average P-wave (SAPW) is a non-invasive quantitative method to determine P-wave duration, an accepted marker for atrial electrical remodeling. Our objective was to determine whether CPAP induces reverse atrial electrical remodeling in patients with severe OSA. Methods: Prospective study in consecutive patients attending the Sleep Clinic at our institution. All patients underwent full polysomnography. OSA-negative and severe OSA were defined as apnea-hypopnea index (AHI) < 5 events/hour and AHI ≥ 30 events/hour, respectively. In severe OSA patients, SAPW was determined pre- and post-intervention with CPAP. In OSA-negative controls, SAPW was recorded at baseline and 4-6 week...
Plantar Fasciitis
Authors: Rachelle Buchbinder
Journal: New England Journal of Medicine (2004)

A 55-year-old overweight woman presents with a three-month history of pain in her right inferior heel. The pain is worse on taking her first steps in the morning. The physical examination is normal except for nonspecific tenderness in the region of the medial calcaneal tubercle. How should the patient be evaluated and treated?
Abstract 4431: Differential Blood Pressure Effect of Naproxcinod Compared with Naproxen on Ambulatory Blood Pressure in Hypertensive Subjects
Authors: Ray Townsend, Neville Bittar, Jeffrey Rosen, William Smith, Andrea Ramsay, Steven Chrysant, Robert Weiss, Hayet Frayssinet, Jacques Djian
Journal: Circulation (2008)
Comparison of Digital Rectal Examination, Transrectal Ultrasonography, and Multicoil Magnetic Resonance Imaging for Preoperative Evaluation of Prostate Cancer
Authors: Manuel Sanchez-Chapado, Javier Angulo, Cristina Ibarburen, Fernando Aguado, Antonio Ruiz, Juan Viaño, Juan M. Garcia-Segura, Jorge Gonzalez-Esteban, Jose M. Rodriguez-Vallejo
Journal: European Urology (1997)
Abstract 4483: Long-Term Clinical Outcomes of 233 Patients who Presented with Definite/Probable Stent Thrombosis
Authors: Tina L Pinto Slottow, Daniel H Steinberg, Probal Roy, Laurent Bonello, Gilles Lemesle, Kimberly Kaneshige, Zhenyi Xue, Rebecca Torguson, Joseph Lindsay, Augusto Pichard, Lowell Satler, William O Suddath, Kenneth Kent, Ron Waksman
Journal: Circulation (2008)

Stent thrombosis (ST) is the most concerning adverse outcome of drug-eluting stent (DES) placement. Clinical outcomes of patients experiencing definite and definite/probable ST by the Academic Research Consortium definitions, among the 9535 patients undergoing unrestricted percutaneous coronary intervention (PCI) with DES since April 2003, were examined. Clinical outcomes up to 3 years following DES implant of the patients with definite or probable ST were compared to those without ST. Baseline demographics were similar. The population was 65.7% male with a mean age of 63.7 years. 104 patients presented with 109 definite ST events. 233 patients were adjudicated to have experienced definite or probable ST events, 50 due to unexplained death within 30 days of DES implantation and 79 due to target vessel myocardial infarction with unknown culprit. Outcomes in both these groups were uniformly poorer with a much higher incidence of death, Q-wave myocardial infarction, and target vessel revascularization up to 3 years when compared to patients who did not experience definite or probable ST. (Table ) DES ST is an infrequent, but at 3 years 2/3 of the patients with DES ST are dying and the remaining are experiencing high morbidity.
The role of nonconserved amino acid residues of the transmembrane (TM) regions in functional modulation of human P-glycoprotein
Authors: Debjani Mandal, Ruma Dey, Apurba Chattopadhyay, Saibal Dey
Journal: Cancer Research (2006)

591  ATP-dependent drug transport by the human P-glycoprotein (Pgp, ABCB1) contributes to cellular resistance against and poor bioavailability of many anticancer and antimicrobial agents. Successful pharmacological intervention of the drug transport function of Pgp could lead to improved efficacy of many therapeutic agents that are otherwise ineffective being substrates of the efflux pump. For strategic designing of such compounds, it is essential to understand the mode of action and sites of interaction of Pgp inhibitors (also called modulators) from the existing repertoire. Towards achieving that goal, we have generated a library of Pgp mutants with single amino acid substitutions (with alanine) in the transmembrane (TM) regions replacing the residues that are not strictly conserved among its mammalian homologs and less likely to be involved in the normal functioning of the protein. The mutant proteins were expressed in insect cells using a baculovirus-mediated expression system, and studied for their ability to interact with modulators of diverse chemical origin. Effect on substrate binding, as well as, ATP hydrolysis were studied in inside-out membrane vesicles. Initial characterization of the mutants allowed us to group the residues under three different classes. Some of the residues contribute to modulation in a selective manner, replacement of which with alanine affected modulatory potential of either the thioxanthenes (such as flupentixol) or the antiarythmics (verapamil), but not both. Whereas, the second group represents residues that play a more general role in modulation, substitution of which by alanine affect modulatory potential of both classes of modulators. Interestingly, the third group comprises amino acid residues that have a selective role, either contributing to modulation of ATP hydrolysis or to substrate interaction, suggesting distinct pathways of communication with the ATP- and the substrate- sites. A more detailed analysis of the effect of thioxanthene derivatives reveals that the residues in TM12 are most likely involved in modulator recognition, where as those in TM6 seem to be responsible for translating the modulatory effects. We are currently extending our studies to correlate the observed effect of the mutations on modulation of ATP hydrolysis and substrate binding to inhibition of drug transport.
Abstract 175: Effects of Dispatcher-Assisted Cardiopulmonary Resuscitation Recommended in the 2005 AHA Guidelines for CPR
Authors: Kei Nishikawa, Ken Nagao, Eizo Tachibana, Tukasa Yagi, Naohiro Yonemoto, Morimasa Takayama, Hiroshi Hiroshi Nonogi, Shinichi Shirai, Takeshi Kimura
Journal: Circulation (2011)

BACKGROUND The AHA 2010 guidelines for cardiopulmonary resuscitation (CPR) recommended that dispatchers should assertively provide compression-only CPR instructions to untrained rescuers. However, it is unclear whether dispatcher-instructed CPR recommended in the AHA 2005 guidelines can improve survival. METHODS We compared the effects of dispatcher-instructed CPR recommended in the 2005 CPR guidelines with those recommended in the 2000 CPR guidelines from the data of the All-Japan Utstein Registry, a prospective, nationwide, observational registry. The study endpoints were return of spontaneous circulation (ROSC) on hospital arrival and 30-day favorable neurological outcome after cardiac arrest. RESULTS Of the 58,448 adult patients with bystander-witnessed out-of-hospital cardiac arrest due to presumed cardiac etiology in the year 2005, 2008 and 2009, 23,165 who received instructions in CPR given by dispatchers over the telephone were included; 17,282 received the instructions of CPR recommended in the 2005 guidelines, and 5,883 received in the 2000 guidelines. The performance of dispatcher-instructed CPR (chest compression plus mouth-to-mouth ventilation or chest compression only) of the 2005 guidelines group showed a higher proportion than that of the 2000 guidelines group (42% vs.33%, p&lt;0.0001), especially those with compression-only CPR (33% vs.18%, p&lt;0.0001). The 2005 guidelines group had significantly higher rates of ROSC and favorable neurological outcome than the 2000 guidelines group in the whole cohort (ROSC; 12.2% vs. 8.4%, p&lt;0.001, favorable neurological outcome; 5.3% vs. 2.9%, p&lt;0.001), and in the subgroups of patients who received compression-only CPR (ROSC; 13.0% vs. 8.6%, p&lt;0.001, favorable neurological outcome; 6.0% vs. 2.6%, p&lt;0.001). The adjusted odds ratios after dispatcher-instructed CPR recommended in the 2005 guidelines was 1.56 (95% CI, 1.37-1.72) for ROSC and 2.17 (95% CI, 1.79-2.65) for favorable neurological outcome. CONCLUSION Dispatcher-instructed CPR recommended in the 2005 guidelines improved ROSC and favorable neurological outcome in adult patients with bystander-witnessed out-of-hospital cardiac arrest due to presumed cardiac etiology.
Chemotherapy and management of tuberculosis in the United Kingdom: recommendations 1998
Authors: T Joint
Journal: Thorax (1998)

<h3>BACKGROUND</h3> The guidelines on chemotherapy and management of tuberculosis in the United Kingdom have been reviewed and updated. <h3>METHODS</h3> A subcommittee was appointed by the Joint Tuberculosis Committee (JTC) of the British Thoracic Society to revise the guidelines published in 1990 by the JTC. In preparing the revised guidelines the authors took account of new published evidence and graded the strength of evidence for their recommendations. The guidelines have been approved by the JTC and the Standards of Care Committee of the British Thoracic Society. <h3>RECOMMENDATIONS</h3> (1) Patients with tuberculosis should be notified. (2) In view of the rising incidence of drug resistance, bacteriological confirmation and drug susceptibility testing should be sought whenever possible. (3) A six month short course regimen, with four drugs in the initial phase, should be used for all forms of tuberculosis, except meningitis, in both adults and children. (4) The fourth drug (ethambutol) in the initial phase can be omitted in certain circumstances. (5) Treatment of all patients should be supervised by physicians with full training in the management of tuberculosis and with direct working access to tuberculosis nurse specialists or health visitors. (6) Advice is given on (a) management in special situations and patient groups, (b) drug interactions, and special precautions and pretreatment screening, (c) chemoprophylaxis for different groups, and (d) the management of single and multiple drug resistance. (7) Advice is given on follow up after treatment and the organisational framework for tuberculosis services. (8) The role of directly observed therapy is discussed. (9) The management of multidrug resistant tuberculosis is explained in outline: such patients should be managed by physicians with special experience and in close liaison with the Mycobacterium Reference Units, and in hospitals with appropriate isolation facilities. (10) Infection control and segregation for such patients and for patients with dual infection with human immunodeficiency virus (HIV) and tuberculosis are covered in an .
Cyclophosphamide, epirubicin and fluorouracil followed by docetaxel (CEF-DOC) as preoperative chemotherapy in primary operable breast cancer: Evaluation of chemotherapeutic response by breast MRI
Authors: S. Nakamura, S. Ohno, M. Toi, Y. Takatsuka, K. Kuroi, H. Iwata, K. Hisamatsu, K. Yamazaki, N. Masuda, F. Akiyama
Journal: Journal of Clinical Oncology (2004)

812 Background: Preoperative systemic chemotherapy (PST) is used increasingly in the treatment of operable breast cancer. The purpose of this study was to evaluate the feasibility and safety as well as clinical and pathological response of Cyclophosphamide, Epirubicin and Fluoraouracil followed by Docetaxel (CEF-DOC) as PST in pts. with operable breast cancer. Especially, chemotherapeutic response was evaluated by breast MRI. Methods:Primary breast cancer pts. with T1c-3N0M0 or T1–3N1M0, age 20–60, PS 0–1 were eligible for this study. Preoperative chemotherapy consisted of 4 cycles of CEF (500mg/m2, 100mg/m2, 500mg/m2) every 3 weeks followed by 4 cycles of DOC (75mg/m2) every 3 weeks prior to surgery (either modified radical mastectomy or breast-conserving surgery). Breast MRI was performed for three times in 30 pts.(prechemo, after CEF and after DOC), and no adjuvant therapy except radiation, hormone therapy was allowed. Results: Since June 2002, 128 pts. were enrolled in this study, and at the time of this analysis, 50 pts. were evaluable for safety and efficacy. Of 400 planned cycles, 96.5% were administered, and median dose intensity (DI) delivered for epirubicin and DOC reached 91% and 86% of planned DI, respectively. The overall clinical response was 74.0% (20% CR, 54% PR), and 8 pts. (18%) resented SD and two PD (8%).. Diagnostic accuracy of breast MRI was 93.3% (28/30). MRI correctly detected multifocal lesion of the disease. Of note, 8 pts. (16%) improved the response of CEF with DOC, and breast conservation was achieved in 88% of pts. Conclusions: This regimen is active and well tolerated, and breast MRI is a valuable method to monitor accurate response of chemotherapy and helpful to determine appropriate surgical planning. No significant financial relationships to disclose.
Abstract 9409: Aging Inhibits Angiogenic Response in a Rat Model of Hindlimb Ischemia: A HUR-VEGF Dependent Mechanism
Authors: Chang-Ning Hao, Jing-Juan Huang, Yi-Qin Shi, Rui-Lin Li, Jun-Li Duan
Journal: Circulation (2014)

Introduction: Human antigen R (HUR) is a RNA stablilizer and its expression decressed in aging organism, however, its downstream signal pathways remain modest clarified. Here, we examined whether HUR plays a role in angiogenic response using an aging rat model of hindlimb ischemia. Methods and Results: Male Sprague-Dawley rats were divided into 2 groups: the young group (12 week-old) and the aging group (96 week-old). The left femoral artery of all rats were excised, and the extent of angiogenesis and collateral vessels in the ischemic limb were examined for 2 weeks. At postoperative day 14, aging rats exhibited impaired angiogenic action (skin temperature, capillary density and angiography) and decreased angiogenic factor expressions (vascular endothelial growth factor [VEGF], hypoxic inducible factor-1α and nitric oxide [NO]) in ischemic muscles. The protein expression of HUR as well as endothelial nitric oxide synthetase (eNOS) phosphorylation were significantly inhibited in aging rats as well. In vitro, we applied anti-HUR small interfering RNA to transfect human umbilical vein endothelial cells (HUVECs). The results showed that transfected HUVECs exhibited decreased the capacities of VEGF/NO production, tube formation and apoptotic resistence compared with control. Conclusions: Our results domenstrated that the down-regulation of HUR plays a key role in aging-related poor angiogenic response.
Potential role of sialyl Lewisa in adhesion and invasion of cholangiocarcinoma cell line
Authors: Sopit Wongkham, Apa Juntavee, Banchob Sripa, Ake Pugkhem, Vajarabhongsa Bhudhisawasdi
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1308 

Sialyl Lewisa or carbohydrate antigen (CA) 19-9, is a glycosphingolipid of the Lewis blood group that has been proposed as a useful marker for epithelial type gastrointestinal cancers, especially those of the pancreas and biliary tract. It is known to be a ligand of E-selectin that may play role in the adhesion of cancer cells to endothelial cells and resulting in hematogenic metastasis. Patients with cholangiocarcinoma (CCA) always present with high metastasis which lead to the poor prognosis and survival. High levels of sialyl Lewisa are frequently detected in serum and tissues of CCA patients. This project was aimed to investigate the role of sialyl Lewis a in the adhesion and transmigration of CCA cells via E-selectin mediated endothelial cells. KKU-M213, a CCA cell line with high expression of sialyl Lewis a, and HUVEC (human umbilical vein endothelial cells) stimulated with IL-1B, were used in this study. The transmigration assay was performed using a double chamber with monolayer of HUVEC cultured on the filter of upper chamber. The adhesion and transmigration of KKU-M213 to E-selectin-stimulated HUVEC were significantly enhanced comparing to those of non stimulated (p<0.01). This observation was significantly inhibited by either monoclonal antibody against sialyl Lewisa (p<0.01) or E-selectin (p<0.05). The adhesion and transmigration activities were also reduced by inhibiting glycosylation of the cancer cells with benzyl-αGalNAC which reduced the expression of sialyl Lewisa. These results suggested that sialyl Lewisa plays a significant role in metastasis of cholangiocarcinoma by enhance cell adhesion and transmigration via E-selectin mediated endothelial cells. This may lead to the identification of new targets of drugs for anti-metastasis of cholangiocarcinoma. This project is supported in part by the research grant of Faculty of Medicine, and the Graduate School (through A. Jantavee), Khon Kaen University, 2003.
Surgical Aspects of Intrahepatic Artery Therapy
Authors: John E. Niederhuber
Journal: Liver Cancer (1985)

The concept of regional chemotherapy for metastatic and primary liver cancer has been widely tested since its introduction in the 1950s [1–18]. From these numerous reports it was clear that the potential for success, as measured by improved survival, was dependent upon overcoming a number of technical problems. These technical problems significantly limited the duration of regional drug delivery [4–6, 10–18]. Early in 1979, we had the opportunity to adapt a totally implantable drug delivery system (Infusaid, Corporation, Norwood, MA.) for hepatic artery chemotherapy [19–23], Over the past five years we have implanted this device in over 200 patients [23–27]. Based on this experience, a number of critical technical axioms appear paramount to successful treatment. Clearly, the most important of these observations has been the necessity for attaining total liver perfusion and the importance of avoiding extrahepatic perfusion.
Abstract 19736: Patients With Paroxysmal and New Onset Persistent Atrial Fibrillation and Severe Left Atrial Scarring: Outcome With and Without Ablation of Extra Pulmoany Veins Triggers
Authors: Luigi Di Biase, Dhanunjay Lakkireddy, Prasant Mohanty, Subbareddy Vanga, Venkat Nagarajan Darbhamulla, Javier Sanchez, J. Joseph Gallinghouse, Shane Bailey, Jason Zagrodzky, Rodney Horton, Steven Hao, Richard Hongo, Salwa Beheiry, Claude Elayi, Sanghamitra Mohanty, Rong Bai, Douglas Gibson, J. David Burkhardt, Andrea Natale
Journal: Circulation (2010)

Introduction: Severe left atrial (LA) scarring has been shown to be an independent predictor of ablation failure for atrial fibrillation. The aim of this study was to compare the outcome in patient...