tbuckley/cabot-search huggingface dataset:
Abstract 18440: Cardiac Output Reserve Predicts Exercise Capacity and Need for Surgery in Aortic Stenosis
Authors: Matthew Lumley, Rupert Williams, Michelle Navales, Denise Parkin, Helen Rimington, Michael Marber, Ronak Rajani, John Chambers, Divaka Perera
Journal: Circulation (2014)

Background: The development of symptoms in patients with aortic stenosis (AS) relates inconsistently with echocardiographic measures of stenosis severity. This is a reflection of the dynamic interaction between the valve and ventricle on exercise, which is not captured by any single parameter. We hypothesised that cardiac output reserve (COR), the ratio of cardiac output at peak exercise to cardiac output at rest, would predict exercise capacity (EC) and the need for aortic valve surgery. Methods: 40 patients with moderate-severe AS, were prospectively recruited. All patients underwent resting transthoracic echocardiography, modified Bruce exercise treadmill testing (ETT), B-type natriuretic peptide measurement and bicycle exercise stress echocardiography. EC was defined by exercise duration during the ETT. The decision to refer the patient for surgery was made by the specialist valve team who had access to all data but were blinded to COR results. Regression analysis was performed using independent variables shown to correlate with each outcome measure on univariate analysis. Results: The mean±SD of the EC was 645±294s, aortic valve area (AVA) 0.92±0.28cm 2 and COR 1.86±0.39. 22 of the 40 patients were referred for surgery. Exercise Capacity: On univariate analysis, resting AVA or mean/peak pressure gradient (AVG) did not correlate with EC. EC significantly correlated with COR (r = 0.71, p &lt; 0.000001), age (r = -0.63, p &lt; 0.00005), BNP (r = -0.49, p = 0.03), peak AVG at maximal exercise (peak AVG ex ) (r = 0.32, p = 0.04) and tissue Doppler lateral mitral valve annulus systolic velocity, Sa (r = 0.32, p = 0.05). By multiple linear regression, only COR (β = 0.5, p = 0.0004) and peak AVG ex (β = 0.3, p = 0.09) were predictive of EC. Referral for Surgery: By ROC analysis, a COR of 1.8 (AUC 0.87, 95% CI 0.77-0.98) best predicted the need for surgery. Energy loss index at maximal exercise, meanAVG at rest and AVA at maximal exercise were also predictors of need for surgery. By binary logistic regression, only COR was predictive of the need for surgery (OR 0.02, 95% CI 0.00001-0.53, p = 0.03) Conclusion: Cardiac Output Reserve is a novel index that predicts exercise capacity and the need for surgery in moderate to severe AS.
Repression of vascular endothelial growth factor-A over-expression in glioblastoma cells using engineered zinc-finger transcription factors
Authors: Andrew W. Snowden, Lei Zhang, Fyodor Urnov, Carolyn Dent, Andrew R. McNamara, Yann Jouvenot, Steven H. Zhang, Xiaohong Zhong, Edward J. Rebar, Andrew C. Jamieson, Siyuan Tan, Casey C. Case, Alan P. Wolffe, Philip D. Gregory
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1447 

Angiogenesis is of critical importance to tumor progression and therefore is an attractive target in the treatment of cancer. The pro-angiogenic Vascular Endothelial Growth Factor A (VEGF-A), a potent effector of angiogenesis, is over-expressed in a variety of human cancers including highly invasive brain tumors. In this study, we have applied engineered zinc-finger protein transcription factors (ZFP TFs) to the regulation of VEGF-A expression in human cancer cell lines. We show that ZFP TFs containing either the ligand-binding domain of thyroid hormone receptor or its viral relative vErbA are potent transcriptional repressors of VEGF-A expression. The engineered ZFP chimera specifically binds its target site within the VEGF-A promoter in vitro and in vivo and represses in a HDAC dependant manner via targeted deacetylation of promoter nucleosomes. The therapeutic relevance of ZFP-driven VEGF-A repression was addressed using the highly tumorigenic glioblastoma cell line U87MG. Despite the aberrant over-expression of VEGF-A in this cell line, engineered ZFP TFs were able to repress the expression of this gene by >20-fold. Furthermore, the levels of VEGF-A following ZFP TF-mediated repression were comparable to those of a non-angiogenic cancer line, U251MG, suggesting that this degree of repression would be sufficient to suppress tumor angiogenesis. The use of ZFP-mediated recruitment of alternative repression domains and activities which may confer long term, epigenetic repression; such as DNA methylation, histone H3 lysine 9 methylation and HP1 recruitment in the repression of VEGF-A transcription will also be discussed.
Targeted Temperature Management for Cardiac Arrest
Authors: Nathan S. Deal, Robert B. Schock, W. Frank Peacock
Journal: JAMA Neurology (2015)

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 Neurology HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Neurology journal
From metapsychology to molecular biology: explorations into the nature of anxiety
Authors: Eric R. Kandel
Journal: American Journal of Psychiatry (1983)

Through the use of animal models, specific forms of mentation can now be explored on the cellular and molecular levels. Chronic anxiety and anticipatory anxiety in humans are closely paralleled by two forms of learned fear in the sea snail Aplysia: sensitization and aversive classical conditioning. In Aplysia's simple nervous system it is possible to delineate how the two forms are acquired and maintained. Both rely on the mechanisms of presynaptic facilitation. An augmented form of presynaptic facilitation accounts for the associative component of conditioning. These findings suggest that a surprisingly simple set of cellular and molecular mechanisms in various combinations may underlie a wide range of both adaptive and maladaptive behavioral modifications.
Case 6-2015
Authors: Michael R. Wessels, Kathryn S. Brigham, Alfred DeMaria
Journal: New England Journal of Medicine (2015)

A 16-year-old boy presented with a 3-week history of cough and nasal congestion and a 3-day history of severe coughing spells, post-tussive emesis, and trouble breathing. A chest radiograph was normal. A diagnostic test was performed.
Progesterone regulation of hTERT transcription in human endometrial cancer cells.
Authors: Victoria L. Bae-Jump, Chunxiao Zhou, Paola A. Gehrig, John F. Boggess
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

5352 

Objectives: In the normal endometrium, progesterone antagonizes the actions of estrogen and inhibits estrogen-induced cellular proliferation. Consequently, progestins have had some therapeutic benefit in the treatment of endometrial cancer. Telomerase activity is dynamic throughout the menstrual cycle and is highest during the proliferative phase under the influence of estrogen and then falls during the secretory phase under the influence of progesterone. Despite this observation, little is known regarding the role of progesterone in the control of telomerase expression. Thus, our goal was to determine progesterone’s role in regulation of telomerase activity in progesterone receptor (PR)-positive endometrial cancer cell lines. Mehods: In our lab, Ishikawa and ECC-1 cells have been previously shown to be estrogen receptor (ER) and PR-positive, and HEC-1B and RL 95-2 cells to be ER and PR-negative. Telomerase activity was assayed using a PCR-based telomeric repeat amplification protocol (TRAP) after cells were exposed to estradiol (E2), medroxyprogesterone acetate (MPA) or both. hTERT mRNA expression was assessed by real-time RT-PCR. To determine whether progesterone regulates transcripton of the hTERT gene, transient expression assays using luciferase reporter plasmids containing varying lengths of the 5’ promoter region of the hTERT gene were performed. Results: Among the PR-positive endometrial cancer cell lines, E2 (10−5 - 10−7 M) increased telomerase activity and hTERT mRNA expression in a dose-dependent manner. In contrast, MPA (10−6 M) inhibited E2 induced telomerase activity in the PR-positive endometrial cancer cell lines by 24 hours. This effect was not seen in the PR-negative endometrial cancer cell lines. hTERT mRNA levels were decreased parallel to suppression of telomerase activity. Luciferase assays demonstrated that exposure to MPA inhibited E2-induced activation of the hTERT promoter which contains two putative estrogen response elements (EREs) but no progesterone response elements (PREs). Conclusions: We provide evidence that progesterone suppresses estrogen-induced hTERT mRNA expression in PR-positive endometrial cancer cell lines. Downregulation of the PR and reactivation of telomerase activity are thought to occur in advanced stages of endometrial cancer; and thus, may be related. Further work focused on the interaction between progesterone, estrogen and telomerase may provide insight into endometrial carcinogenesis as well as the underlying molecular mechanisms of progestins as a targeted therapy for this estrogen-dependent tumor.
Abstract 1542: Value of High Output Pacing in Mapping of Post-Infarction Ventricular Tachycardia
Authors: Jean-Francois Sarrazin, Eric Good, Michael Kuhne, Darryl Wells, Nagib Chalfoun, Thomas Crawford, Alan Wimmer, Sujoya Dey, Warangkna Boonyapisit, Hakan Oral, Fred Pelosi, Krit Jongnarangsin, Aman Chugh, Fred Morady, Frank Bogun
Journal: Circulation (2007)

Introduction: Identification of critical isthmus sites for post-infarction ventricular tachycardia (VT) ablation can be challenging. Unexcitable scar during pacing can identify one of the borders of the re-entry circuit. This area however is not thought to be critical to the circuit. Because of current-to-load mismatch, higher power might be required in order to obtain capture of individual surviving muscle bundles within scar tissue. The purpose of this study was to evaluate the value of high output capture of scar tissue in patients with post-infarction VT. Methods: In a consecutive series of 18 patients (15 men, age 62 ± 9, EF 0.28 ± 0.15) with post-infarction VT, mapping was performed using an electroanatomic mapping system. A voltage map was obtained during sinus rhythm and bipolar pace-mapping was performed in areas with low voltage (&lt; 1.5 mV) with an output of 10 mA at a pulse width (PW) of 2 ms. High output capture was defined when capture at these settings failed but capture could be achieved with increased output. If there was no capture at the initial settings, output was increased to 20 mA at a PW of 2 ms, eventually the PW was increased up to 10 ms as required to achieve capture. A critical isthmus was defined as a site with a matching pace-map, and/or matching stimulus-QRS to electrogram-QRS intervals in the presence of concealed entrainment, and/or mechanical termination of VT and failure to induce VT after radiofrequency ablation. Results: Focal areas with high output capture could be observed in 10/18 (56%) patients. In 9/10 patients in whom high output capture was present (mean output: 20 mA; mean pulse width: 7.4 ms), this area was critical for the re-entry circuit of 10 VTs (cycle length 444 ± 72 ms). A total of 77 VTs (cycle length 390 ± 115 ms) was induced in these patients. Forty-three isthmus sites could be identified and effectively ablated for 56 of the VTs. During a follow-up of 4.9 ± 5.3 months 2 patients had VTs that were not targeted during the ablation. Conclusions: High output pacing is helpful in identifying critical areas of post-infarction VT that otherwise might be missed.
Role of E-selectin in the modulation of metastatic phenotype
Authors: Gregorio Seidita, Anna Maria Flugy, Paolo Colomba, Valentina Di Caro, Giacomo De Leo, Riccardo Alessandro
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

3029 

The selectins are a family of intercellular adhesion molecules with three members: E-, P- and L-selectin. E-selectin (ELAM-1, CD62E) is a type Ia transmembrane protein containing lectin-like and endothelial growth factor-like domains, followed by short cysteine-rich repeats. Absent in resting epithelium, E-selectin is rapidly expressed in the vascular lining during inflammation. Indeed, activation of endothelial cells by proinflammatory cytokines results in the cell surface appearance of E-selectin, facilitating leukocyte rolling and extravasation through activated endothelium. During a screening of gene expression in several human colon cancer cell lines we surprisingly identified E-selectin, as a molecule that was modulated in response to TNF-α. The up-regulation of E-selectin was also confirmed at the protein level with a mAb against human E-selectin. In order to better understand the role of E-selectin in the expression of tumor phenotype, we transfected T84 human colon cancer cells with the full length E-selectin cDNA and cDNA coding for the E-selectin shedded domain. We selected clones with a variable expression of the proteins and tested them for their ability to form aggregates, migrate, establish colonies in soft agar as well as to adhere to extracellular matrix substrates. The results we obtained strongly support the hypothesis that E-selectin plays an active role in metastatic cascade not only determining the extravasation site for tumor cells but also modulating growth rate and survival.

Acknowledgments

This work was supported by Italian Association for Cancer Research (AIRC)
Dysfunctional breathing and asthma
Authors: S. J C Davies, P. R Jackson, L. E Ramsay, D. Kuiper, M. Thomas
Journal: BMJ (2001)

Editor—Thomas et al report an appreciable prevalence of dysfunctional breathing in adults with asthma and discuss the scope for wider use of breathing therapy.1 Neither Thomas et al nor Keeley and Osman in their editorial2 consider whether such symptoms might occur equally often in the normal population or represent panic attacks and panic disorder, well defined entities common in otherwise healthy people. Without a control group their study is incapable of identifying the prevalence of dysfunctional breathing associated specifically with asthma.

Dysfunctional breathing and the hyperventilation syndrome are by no means the same as panic syndromes, but overlap between them may be considerable. Thomas et al acknowledge limitations of the Nijmegen questionnaire.3 This instrument cannot differentiate the “chimeric” hyperventilation syndrome from panic attacks and panic disorder. The 16 items in the Nijmegen questionnaire include “anxiety,” “feeling tense,” and nine of the 13 panic attack symptoms listed in the Diagnostic and Statistical Manual of Mental Disorders, third edition, revised (DSM-III-R). The questionnaire was not defined to attempt to make this distinction. A 23% lifetime prevalence of spontaneous panic attacks has been reported in patients with asthma.4 This figure is not dissimilar to the 29% of asthmatic patients labelled by Thomas et al as having experienced dysfunctional breathing and again suggests appreciable overlap. The lifetime prevalence of asthmatics meeting DSM-III-R criteria for panic disorder in the same study was 9.7%4.

We reported a significant excess of panic attacks and panic disorder among primary care and hospital patients with hypertension compared with matched normotensive people, and 202 of 287 people who had experienced panic attacks related “shortness of breath” or “difficulty catching breath” as symptoms in their worst panic attack.5 The relation of history of panic attacks to a patient's sex in our sample was strikingly similar to that reported for dysfunctional breathing1, with a significant excess in female patients of around 15% in both studies.

The importance of considering panic disorder in a discussion of dysfunctional breathing lies in the availability of treatment of proved efficacy. Thomas et al limit their consideration of therapeutic intervention to breathing therapy. In a patient with recurrent difficult breathing and history suggestive of panic disorder, a much broader range of treatment, from tricyclic antidepressants and selective serotonin reuptake inhibitors to cognitive therapy, may be effective. Failure to identify panic attacks or panic disorder may deprive patients of valuable treatment options, some of which can be instigated in primary care.
Differences in tuberculosis disease among immigrant and native populations
Authors: Diana Badenes, August Supervia, Francisco del Baño, Sabina Herrera, Oriol Pallàs, Roberto Chalela
Journal: European Respiratory Journal (2013)

Introduction: Tuberculosis (TB) is a public health problem although its incidence has declined. In the last decade there has been an epidemiological shift caused by immigrants from high-prevalence countries, HIV infection and immunosuppressive treatments. Barcelona reaches a TB incidence of > 90 per 100,000 inhabitants in some areas.  Methodology: TB disease cases between 2006 and 2012 were retrospectively selected. Data on demographic and clinical characteristics, comorbidities, drug abuse, laboratory tests, radiographic pattern, treatment and resistances were collected.  Results: 222 TB cases were included. 62.6% of the patients were immigrants, and the clinical presentation was pulmonary TB in 76.8%, pleural TB in 23.2% and nodal TB in 7.3% of the cases. These percentages were 86.7%, 19.3% and 2.4%, respectively in native population. No statistical differences were found in clinical presentation, radiographic pattern, treatment resistance or days of stay in hospital.  Conclusions: TB disease in immigrants appears at a lower age than in native patients and in those patients living in group. There are no differences in clinical, radiological presentations and in the development of resistances to treatment. Since immigrant patients showed more smear negativity, this might suggest indication for >3 serial sputum analysis and sustained isolation.
The inhibitory effects of xanthorrhizol against 7,12-dimethylbenz[a]anthracene-induced carcinogenesis in hamster buccal pouch and carcinogen-mediated DNA damage in oral cancer cells
Authors: Kyoung-Ok Hong, Won-Yoon Chung, Jae-Kwan Hwang, Chang-Ki Lee, Kwang-Kyun Park, Min-jung Park
Journal: Cancer Research (2004)

Proc Amer Assoc Cancer Res, Volume 45, 2004

1551 

Curcuma xanthorrhiza Roxb. (Zingiberaceae) has been traditionally used for medicine in Indonesia and its anti-tumor and anti-inflammatory activities have been reported. We found in the previous studies that xanthorrizol, one of the active components in C. xanthorrhiza , inhibited the tumor formation in two-stage mouse skin carcinogenesis, induced apoptosis in HL-60 cells and suppressed VEGF-induced angiogenesis in HUVECs. In the present work, the topical application of xanthorrhizol prior to the treatment of 7,12-dimethylbenz[ a ]anthracene (DMBA) significantly reduced both the incidence and the multiplicity of tumors in hamster buccal pouch. Bromodeoxyuridine and terminal deoxynucleotidyl transferase-mediated nick end labeling indices were examined to determine the ratio of cell proliferation to apoptosis in the buccal pouch tissues. In addition, we evaluated the protective effect of xanthorrhizol on DNA damage induced by 4-nitroquinolin 1-oxide (4-NQO), DMBA and several carcinogens closely related to oral carcinogenesis using single cell gel electrophoresis (Comet assay). These effects were compared with that of curcumin, a promising chemopreventive agent isolated from C. longa . Xanthorrhizol- and curcumin-pretreated oral cancer cells showed the markedly decrease of tail DNA(%) compared with 4-NQO-, and DMBA-treated cells, respectively. These findings demonstrate that xanthorrhizol has the chemoprotective potential against oral carcinognenesis and genotoxicity by carcinogens. Furthermore, we are studying the molecular mechanism underlying protective effect of xanthorrhizol on carcinogen-mediated DNA damage.
Abstract 12993: The Association of Resting Heart Rate and Incident Hypertension: The Henry Ford HospITal Exercise Testing (FIT) Project
Authors: Amer I Aladin, Mahmoud Al Rifai, Shereen H Rasool, Steven J Keteyian, Clinton A Brawner, Erin D Michos, Michael J Blaha, Mouaz Al-Mallah, John W McEvoy
Journal: Circulation (2014)

OBJECTIVE: While high resting heart rate (RHR) is associated with cardiovascular disease (CVD), the mechanism is unclear. Given that sympathetic tone is associated with prevalent hypertension (HTN), we sought to determine whether RHR, as a surrogate for cardiac autonomic function, was associated with incident HTN.

METHODS: We analyzed 22,187 individuals without a history of HTN who underwent a clinically indicated exercise stress test between January 1991 and May 2009. Baseline RHR was categorized as  85 beats-per-minute (bpm). Seated RHR was assessed before each stress test. Incident HTN was defined by coding for new onset HTN on claims files on three or more subsequent encounters. Adjusted Cox models were used to study the association of RHR and incident HTN. We tested for effect modification by age and gender.

RESULTS: Mean age was 49 years (SD 12), 55% were men and 21% were black. 90% of patients achieved ≤ 85% of predicted maximal HR during the stress test. Compared to the lowest RHR ( 85 bpm) were more likely to be younger, female, heavier, non-smokers, diabetic, and have a family history of CVD (p 85 bpm was independently associated with risk for incident HTN after adjustment for demographics, cardiac risk factors and peak METS [Hazard ratios= 1.22 (95% CI 1.12-1.32), compared to RHR <70 (TABLE)]. Age, but not gender, was an effect-modifier (p for interaction 0.008). In age stratified analyses the relationship remained significant only in <60 year olds (TABLE).

CONCLUSION: Elevated RHR is an independent risk factor for incident HTN, particularly in persons < 60 years. Whether lifestyle modification or other strategies to reduce RHR can prevent incident HTN in individuals at risk for HTN warrants further study.

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