tbuckley/cabot-search huggingface dataset:
Abstract 4046: N-myc interactor impacts autophagy via modulation of GSK3β/mTOR signaling
Authors: Brandon J. Metge, Aparna Mitra, Lalita A. Shevde, Rajeev S. Samant
Journal: Cancer Research (2014)

Abstract Autophagy is a cellular mechanism for removal of dysfunctional cellular organelles, large protein complexes. It drives a specialized form of program cell death termed as programmed cell death II. Recent studies have demonstrated a prominent role of the process of autophagy in cancer progression and drug sensitivity. Under conditions of stress, cancer cells try to utilize autophagy to leverage a survival advantage; however, excessive autophagy renders cells vulnerable. Our previous work has demonstrated a pivotal role of N-myc interactor(NMI) in impeding breast cancer progression and metastasis. Loss of NMI is one of the key events that precedes and contributes to invasive progression of breast cancer. Here we provide evidence that NMI plays a crucial role in regulation of mTOR signaling ultimately impacting the autophagic response in breast cancer cells. Our initial observations showed that breast cancer cells restored for NMI expression contained more acidic vacuoles as determined by staining with Lysotracker. Further indication of autophagy was evidenced by the formation of distinct punctae in NMI cells upon transfection with GFP-LC3 which was ablated upon treatment with an autophagy inhibitor. Cells restored for expression of NMI showed decreased levels of p62 along with an increased LC3II processing. The mTOR signaling pathway plays a pivotal role in driving the autophagy. We found that p70S6K phosphorylation dramatically decreases in NMI expressing cells indicating an inhibition of mTOR signaling in these cells. Our observations show that active GSK3β, a negative modulator of mTOR, is responsible for mediating the effects of NMI. Conversely, NMI silenced cells showed indication of inactive GSK3β concomitant with activated mTOR signaling. Functionally, NMI mediated sensitization of cells to autophagy rendered breast cancer cells incapable of sustaining stress of cisplatin treatment. The sensitivity of these cells to cisplatin was notably reduced upon inhibition of the autophagic process. This suggests a possible role for autophagy in NMI induced drug sensitivity. Collectively, our results suggest that NMI plays an important role in modulation of autophagy via activation of GSK3β and consequent inhibition of mTOR signaling. Citation Format: Brandon J. Metge, Aparna Mitra, Lalita A. Shevde, Rajeev S. Samant. N-myc interactor impacts autophagy via modulation of GSK3β/mTOR signaling. [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 4046. doi:10.1158/1538-7445.AM2014-4046
A simple genetic test identifies 90% of UK patients with haemochromatosis
Authors: Kjh Robson, M Worwood, JD Shearman, DF Wallace, JS Dooley, AT Merryweather-Clarke, JJ Pointon, Wmc Rosenberg, DJ Bowen, AK Burnett, HA Jackson, S Lawless, R Raha-Chowdhury, J Partridge, R Williams, A Bomford, A Walker
Journal: Gut (1997)

Background-The diagnosis of genetic haemochromatosis (GH) before iron overload has developed is difficult. However a convincing candidate gene for GH, HFE (previously HLA-H), has been described recently.Aims-To determine the prevalence of the haemochromatosis associated HFE mutations C282Y and H63D in United Kingdom affected and control populations.Methods-The prevalence of the HFE C282Y and H63D mutations was determined by polymerase chain reaction amplification and restriction enzyme digestion in a cohort of 115 well characterised patients with GH and 101 controls from the United Kingdom.Results-One hundred and five of 115 (91%) patients with GH were homozygous for the C282Y mutation. Only one of 101 (1%) controls was homozygous for the C282Y mutation and this individual currently shows evidence of iron overload. Two of five patients who did not have either of the two described mutations of HFE had early onset iron overload (ages 16 and 24). One had a family history of cardiac failure and the second was subsequently hospitalised due to cardiac failure. These are the first phenotypic observations for patients without either C282Y or H63D mutation of HFE.Conclusion-This simple genetic test promises to be a highly effective tool in the diagnosis of GH.
ISOLATED (FIEDLER'S) MYOCARDITIS: REPORT OF CASE FIRST MANIFESTED BY ARTERIAL EMBOLI IN EXTREMITIES AND TERMINALLY BY MURAL THROMBI IN THREE OF THE HEART CHAMBERS
Authors: Roger W. Robinson, Frank B. Queen
Journal: Annals of Internal Medicine (1945)

Case Reports1 November 1945ISOLATED (FIEDLER'S) MYOCARDITIS: REPORT OF CASE FIRST MANIFESTED BY ARTERIAL EMBOLI IN EXTREMITIES AND TERMINALLY BY MURAL THROMBI IN THREE OF THE HEART CHAMBERSROGER W. ROBINSON, FRANK B. QUEENROGER W. ROBINSON, FRANK B. QUEENAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-23-5-860 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptAcute isolated myocarditis was first described in 1900 by Fiedler.1It is a rare disease and one in which inflammation of the myocardium is apparently the only important acute lesion in the body. Engelhardt and Bruno,2in a recent review of the literature, collected nine cases from the American and 46 additional cases from the world literature. Various infections have been suspected as causing this disease such as acute upper respiratory infections, influenza, pneumonia, measles, virus infections, syphilis; also toxins have been suggested as etiologic agents circulating in the blood stream from diphtheria or streptococcus infections. Likewise implicated are vitamin...Bibliography1. FIEDLER A: Über akute interstitielle Myokarditis, Centralbl. f. inn. Med., 1900, cci, 212. Google Scholar2. ENGELHARDTBRUNO HTFE: Fiedler's myocarditis, New England Jr. Med., 1943, cclxxxviii, 222-224. CrossrefGoogle Scholar3. HELWIGSCHMIDT FCEC: A filter-passing agent producing interstitial myocarditis in anthropoid apes and small animals, Science, 1945, cii, 31-33. CrossrefGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: *Received for publication October 16, 1944. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byIdiopathic Myocardial Failure in the Last Trimester of Pregnancy and the Puerperium 1 November 1945Volume 23, Issue 5Page: 860-868KeywordsBacteremiaDiphtheriaInfectious diseasesMyocarditisRiversStreptococcal infectionsStreptococcusSyphilisToxinsUpper respiratory tract infections ePublished: 1 December 2008 Issue Published: 1 November 1945 PDF downloadLoading ...
Abstract 12800: Increased Carotid Intima-Media Thickness and Presence of Carotid Plaque are Associated With Increased Stroke Incidence in Atrial Fibrillation: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Wobo Bekwelem, Faye L Lopez, Elsayed Z Soliman, Sunil Agarwal, Gregory Y Lip, Wei Pan, Aaron R Folsom, Alvaro Alonso, Lin Y Chen
Journal: Circulation (2014)

Purpose:  Increased carotid intima-media thickness (cIMT) and presence of carotid plaque are risk factors for incident ischemic stroke in the general population. We sought to determine whether these carotid indices are independently associated with incident ischemic stroke and improve risk prediction of stroke over and above the CHA 2 DS 2 -VASc variables in participants with incident atrial fibrillation (AF) in the ARIC study.   Methods:  We included participants who developed AF within 5 years after carotid evaluation (1987-98), not on warfarin, and without prior stroke at the time of AF diagnosis. Incident AF was ascertained from study ECGs and hospitalization discharge codes, and ischemic stroke was physician-adjudicated from medical chart review through the end of 2011. We used multivariable Cox models to assess association between carotid indices and ischemic stroke. We determined improvement in model discrimination by calculating the C statistic, net reclassification improvement (NRI) and relative integrated discrimination improvement (IDI) for 10-year risk prediction.   Results:  During a mean follow-up of 8.5 years, there were 724 incident AF cases (mean age 63, 40% female, 16% black), of whom 81 (11%) subsequently developed stroke. Increased cIMT and presence of carotid plaque were independently associated with increased risk of stroke in AF (Table). The addition of cIMT + plaque marginally improved discrimination of a model based on the CHA 2 DS 2 -VASc variables: C statistic (95% CI) improved from 0.685 (0.623-0.747) to 0.698 (0.638-0.759). The NRI and IDI for cIMT + plaque were statistically significant: 0.131 (0.01-0.226) and 0.101 (0.002-0.226), respectively (both p   Conclusion:  Increased cIMT and presence of carotid plaque are associated with increased risk of stroke in AF and modestly improve risk prediction of stroke. Further research is needed to evaluate whether carotid indices should be considered in current risk scores for stroke in AF.
Is the watanabe heritable hyperlipidemic rabbit a suitable experimental model for percutaneous transluminal coronary angioplasty in humans?
Authors: Hideki Wanibuchi, Koert P. Dingemans, Anton E. Becker, Makiko Ueda, Takahiko Naruko, Shinichi Tanizawa, Kenji Nakamura
Journal: Journal of the American College of Cardiology (1993)
654. rAAV Mediated Ribozyme Delivery Targeting Mouse Rhodopsin
Authors: Marina Gorbatyuk, J. J. Pang, William W. Hauswirth, Alfred S. Lewin
Journal: Molecular Therapy (2004)

Our long term goal is to develop ribozymes that may function in a “digest and replace” gene therapy strategy for autosomal dominant retinitis pigmentosa (ADRP) caused by mutations in the gene for rod cell opsin. Previously, we have shown that ribozymes Rz397 and Rz448 designed to cleave canine rhodopsin (RHO) mRNA effectively digest that mRNA in tissue culture experiments. In the present experiments, we test whether these ribozymes would function in vivo in mice. Mouse RHO mRNA matches perfectly with Rz397 but contains a mismatch with Rz448 that should diminish its activity. Genes for both ribozymes were cloned in an AAV vector under the control of the murine opsin proximal promoter and were packaged in AAV2 capsids. Both wild-type C57-Bl/6 (RHO +/+) and rhodopsin knockout hemizygotes (RHO+/−) were treated. Virus was injected in the right eye at postnatal day 6 (0.5 μl) or at postnatal day 30 (1 μl). In the P30 injections, animals were also injected with lactated Ringers solution in the left eye. At 1 and 2 months following injection, animals were analyzed by simultaneous full-field electroretinography (ERG) for a- and b-wave amplitudes. Mice were then sacrificed and enucleated. Retinal extracts were then analyzed for RHO RNA levels (by RT-PCR) and protein levels by western blot. To visualize rhodopsin reduction, immunocytochemistry and in situ hybridization were also performed. For immunocytochemistry, eyes were fixed in 4% paraformaldehyde and 10 μm cryosections were incubated with a 1:1000 dilution of primary antibody. Antibody-antigen complexes were detected with Cy3-conjugated anti-mouse IgG antibodies (1:100). In situ hybridization with a 33P-labeled RNA probe to murine rhodopsin was performed using the mRNA Locator Kit and the In Situ Hybridization Kit from Ambion, Inc. Selected slides were dipped in photographic emulsion and quantitative analysis of hybridization was made both on film and on emulsion-dipped slides. RHO +/− injected withAAV-Rz397 at P6 showed a 50% reduction in b-wave amplitudes of injected eyes relative to the uninjected contralateral eye (P<0.05). However, injection of RHO (+/−) animals at one month and of RHO (+/+) animals at either age had no impact on ERG. AAV-Rz 448 had a lesser impact on b-wave amplitudes of the hemizygous animals. Western blot and RT-PCR analysis indicated a 50% reduction of RHO protein and mRNA in injected eyes of both RHO (+/+) and RHO (+/−) mice. These results were confirmed by in situ hybridization and immunocytochemistry. AAV-Rz397 could lead to significant (50%) reduction of rhodopsin mRNA and protein, though this affected ERG amplitudes only in hemizygous rhodopsin knockout mice. Since this ribozyme is less catalytically active with the canine mRNA than Rz448, we expect both ribozymes to be useful in treating canine models of ADRP.
Retinal pigment epithelium translocation after choroidal neovascular membrane removal in age-related macular degeneration 3 3The authors have no proprietary or financial interest related to this manuscript.
Authors: Paulo E Stanga, Andres Kychenthal, Frederick W Fitzke, Anthony S Halfyard, Roger Chan, Alan C Bird, George W Aylward
Journal: Ophthalmology (2002)
Abstract 4773: Racial Disparity In Outcomes After CABG Is Not Neutralized By Off Pump Techniques
Authors: William A Cooper, Vinod Thourani, Omar Lattouf, Edward Chen, Cullen Morris, David Vega, Thomas Vassiliades, Patrick Kilgo, John Puskas
Journal: Circulation (2008)

Introduction : Race has been shown to be an independent risk factor for operative mortality following coronary artery bypass grafting (CABG). This study sought to determine the extent to which race is a risk factor for adverse events and long-term mortality following CABG and whether off-pump surgery (OPCAB) modifies that risk. Methods: The STS Adult Cardiac Database at a single academic institution was queried for all primary isolated CABG patient records from 1997–2007. A propensity score was formulated based on 51 pre-operative risk factors to balance the patient groups with respect to treatment assignment (OPCAB or CABG on CPB). Multivariable logistic regression was used to assess the impact of African-American (AA) race and OPCAB on in-hospital outcomes (death, stroke, MI, and their composite, MACE). A Cox proportional hazards regression model and Kaplan-Meier curves determined whether AA race impacted long-term all-cause mortality. Interaction terms were constructed to test whether OPCAB surgery produces different results in AA patients than in Caucasian (CAUC) patients. Results: There were 12,874 consecutive CABG patients, including 2033 (15.8%) AA and 10,841 (84.2%) CAUC patients. AA patients had higher baseline rates of hypertension, diabetes, and renal failure, and suffered higher risk-adjusted incidence of death, stroke and MACE than Caucasian patients.. Risk-adjusted survival at 3, 5, and10 years for AA (87.5%, 81.4%, 63.8%) was significantly lower than for CAUC (90.7%, 85.2%, 67.1%, p&lt;0.001). Both AA patients (AOR 0.77, CI 0.44 –1.36) and CAUC patients (AOR 0.72, CI 0.53– 0.99) who had OPCAB had lower risk-adjusted odds of MACE than their racial counterparts who had CABG on CPB. No interactions existed which suggest that OPCAB has the same effect in AA as it does in CAUC. Conclusions: OPCAB is similarly beneficial to both race groups in reducing perioperative morbidity. Short and long-term outcomes are significantly worse in AA than Caucasian patients.
Abstract 19039: Prediction of the Chemoreflex Sensitivity by Common Clinical Variables in Systolic Heart Failure
Authors: Gianluca Mirizzi, Andrea Ripoli, Alberto Giannoni, Giuseppe Vergaro, Francesca Bramanti, Giovanni Iudice, Valentina Raglianti, Alberto Aimo, Michele Emdin, Claudio Passino
Journal: Circulation (2014)

Background: Increased peripheral and central chemoreflex sensitivity, as assessed by the hypoxic or hypercapnic ventilatory response (HVR and HCVR, respectively) are two key determinants of heart failure (HF) progression leading to adrenergic activation, arrhythmias and cardiac mortality, thus making them potential therapeutic targets. Their assessment is however technically demanding and uncomfortable for HF patients. Therefore, to increase the awareness of the chemoreflex gain in a clinical scenario, we tried to define a model of chemoreflex prediction starting from standard biohumoral and instrumental variables. Methods and results: 191 patients with stable systolic HF (left ventricular ejection fraction - LVEF - <50%) underwent chemoreflex assessment by rebreathing technique to calculate both HVR and HCVR. All patients underwent clinical and neurohormonal evaluation, echocardiography, cardiopulmonary exercise test (CPET) and a daytime cardiorespiratory monitoring for breathing pattern evaluation. Rega...
Within the System of No-System
Authors: R L Ferrer
Journal: JAMA (2001)

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
Abstract 15316: Impact of Left Ventricular Systolic Function on Blood Pressure Lowering Effects in Hypertensive Patients With Coronary Artery Disease: the Hij-create Sub-study
Authors: Hiroshi Ogawa, Erisa Kawada-Watanabe, Hisao Otsuki, Shintaro Haruki, Noriko Kikuchi, Jun-ichi Yamaguchi, Nobuhisa Hagiwara
Journal: Circulation (2014)

Purpose: To evaluate the relationship between left ventricular systolic function and blood pressure (BP) lowering effects in hypertensive patients with coronary artery disease (CAD) in the substudy of the HIJ-CREATE trial.

Methods: HIJ-CREATE was a multicenter, prospective, randomized, controlled study that compared the effects of candesartan-based therapy with those of non-ARB-based standard therapy on major adverse cardiac events (MACE) in 2,049 hypertensive patients with angiographically documented CAD. Left ventricular ejection fraction (LVEF) was determined by contrast ventriculography, radionuclide ventriculography, or echocardiography on enrollment in this trial. Titration of antihypertensive agents was performed to reach the target BP of <130/85 mmHg. The primary endpoint was the time to first MACE. Incidence of endpoint events in addition to office BP was determined during the scheduled 6, 12, 24, 36, 48, and 60 month visits. Achieved BP were defined as the mean value of systolic BP in patients who did not meet with MACE and the mean value of systolic BP prior to MACE in those who met with MACE during follow-up.

Results: Participants were divided into 3 groups based on LVEF; < 45% (n=386), 45% < <55% (n=524), and ≤ 55% (n=999). Percutaneous coronary interventions had been performed in 86.0% for the lowest, 80.9% for the second, and in 80.2% for the normal LVEF group patients. During a median follow-up of 4.2 years (follow-up rate of 99.6%), event rates were 30.6% for the lowest, 27.6% for the second, and 24.0% for the normal

LVEF group patients. The relationships between achieved systolic BP and the incidence of MACE did not follow J-shaped except for normal LVEF group patients (Figure).

Conclusions: Although the results of the present study did not confirm “the lower, the better” theory in BP lowering therapy for hypertensive patients with CAD, our results may highlight the significance of intensive BP lowering in hypertensive patients with CAD and reduced LVEF.

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Looking forward: Clinical governance and the drive for quality improvement in the new NHS in England
Authors: G. Scally, L. J Donaldson
Journal: BMJ (1998)

Three groups (N = 8) of rats received five 10-trial sessions of one-way avoidance training in which each trial was initiated by a 10-sec tone stimulus and terminated either by a shuttle response during the tone (avoidance) or by a response during the electric shock (escape). Rats in groups treated with pimozide (0.5 or 1.0 mg/kg i.p.) failed to acquire to avoidance response although they escaped readily when shock was presented, whereas control rats consistently avoided the shock. The same rats then received several sessions of food-reinforced lever-pressing in a different apparatus; no drugs were given during these sessions. When responding had stabilized, the tone that had signalled shock in the avoidance sessions was presented for a 1-min period. A significant decrease in responding during the tone was observed in all groups when compared to unshocked controls, demonstrating that the pimozide-treated rats, although failing to acquire the avoidance response in the shuttle box, had learned the association between the tone and shock. The results suggested that the neuroleptic-treated animals failed to avoid because of a deficit in the ability to initiate responses rather than a deficit in associative learning.
Physician Specialty Board Certification
Authors: Todd Lang
Journal: JAMA (2004)

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