tbuckley/cabot-search huggingface dataset:
Rare, Protein-Altering Variants in <i>AS3MT</i> and Arsenic Metabolism Efficiency: A Multi-Population Association Study
Authors: Dayana A. Delgado, Meytal Chernoff, Lei Huang, Lin Tong, Lin Chen, Farzana Jasmine, Justin Shinkle, Shelley A. Cole, Karin Haack, Jack Kent, Jason Umans, Lyle G. Best, Heather Nelson, Donald Vander Griend, Joseph Graziano, Muhammad G. Kibriya, Ana Navas-Acien, Margaret R. Karagas, Habibul Ahsan, Brandon L. Pierce
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Common genetic variation in the arsenic methyltransferase (AS3MT) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine.Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated.OBJECTIVES: We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants.METHODS: We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, n = 2,434), Strong Heart Study (SHS, n = 868), and New Hampshire Skin Cancer Study (NHSCS, n = 666).We assessed the collective effects of rare (allele frequency <1%), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32region, age, sex, and population structure).RESULTS: We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants.DMA% was 6-10% lower in carriers compared with noncarriers in HEALS [b = -9:4 (95% CI: -13:9, -4:8)], SHS [b = -6:9 (95% CI: -13:6, -0:2)], and NHSCS [b = -8:7 (95% CI: -15:6, -2:2)].In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [b = -8:7 (95% CI: -11:9, -5:4)].DISCUSSION: Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME.Although a small percentage of the population (0.5-0.7%) carry these variants, they are associated with a 6-10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds.
Safety And Efficacy oF Hot Versus Cold Avulsion for Treatment Of Residual, Non-Lifting Colonic Polyps During EMR Procedure
Authors: PA Senada, H Pohl, M Raimondo, V Gomez, B Brahmbhatt, E Bouras, A Gavric, DJ Yang, A Singh, S Ngamruengphong, JA Gill, D von Renteln, S Gordon, MB Wallace
Journal: Endoscopy (2021)

Aims Endoscopic mucosal resection (EMR) of removal of large (≥20mm) colorectal polyps may be challenging in the presence of submucosal fibrosis. Avulsion with a biopsy forceps has been used to treat fibrotic areas, either with (hot) or without electrocautery (cold). We aimed to compare safety and efficacy of hot and cold avulsion to remove residual polyp during EMR.
111In-labeled platelet scintigraphy and two-dimensional echocardiography for detection of left atrial appendage thrombi. Studies in a new canine model.
Authors: B FVandenberg, J ESeabold, G RConrad, RKieso, JJohnson, KFox-Eastham, JPonto, PBruch, R EKerber
Journal: Circulation (1988)

111In-labeled platelet scintigraphy and two-dimensional echocardiography were performed in 40 dogs to determine the ability of the two techniques to detect left atrial appendage thrombi. Thrombi were induced in 33 dogs that were classified into two groups,  or chronic, according to the time of labeled-platelet injection after thrombus induction. In the acute group (17 dogs), platelets were injected 24 hours after thrombus induction. In the chronic group (16 dogs), platelets were injected 4-8 days after thrombus induction. Sham thoracotomies were performed on seven additional control dogs who did not receive thrombin injections. Analog and blood pool-corrected 111In-labeled platelet scintigraphy images were obtained 4-72 hours later. Closed-chest two-dimensional echocardiography was performed before thoracotomy and repeated at the time of scintigraphy. The location and size of each thrombus were verified at autopsy. Two-dimensional echocardiography detected three of 17 acute (mean volume, 1.2 +/...
PTH-066 Aspirin, nsaids, and dysplastic colonic polyps – lessons from bowel cancer screening
Authors: Ali Taha, Caroline McCloskey, Theresa Craigen, Debbie Callaghan, MrRobert Diament, Wilson Angerson
Journal: Endoscopy (2018)

<h3>Introduction</h3> Studies on bowel cancer chemoprevention have been limited by the failure to distinguish between the activities of low-dose aspirin and standard non-steroidal anti-inflammatory drugs (NSAIDs). Also, little is known about the activities of these agents in bowel cancer screening programs. We, therefore, aimed to assess the numbers and sizes of polyps/cancers detected in bowel cancer screening of patients using low-dose aspirin (75-mg/day), NSAIDs, and controls. <h3>Methods</h3> Guaiac peroxidase faecal occult blood test kits were sent to 71 026 local residents, aged 50–74 years, over the 12 calendar months of 2016: 38 799 subjects filled in and returned the kits. Those with positive kits (n=849) were interviewed and invited for colonoscopy. Their colonoscopic findings were classified according to their use of aspirin, NSAIDs, or neither. Only dysplastic or cancerous lesions were analysed. The Mann-Whitney test and Fisher's exact test were used as appropriate. Odds ratios were adjusted for age and sex by logistic regression. <h3>Results</h3> DEMOGRAPHY: 528 subjects were colonoscoped at one single centre. The aspirin group (n=112) had 74 (66%) males and a median age of 68 years. The NSAID group (n=46) had 23 (50%) males and a median age of 58 years. The control group, not using either of these agents (n=370), had 207 (56%) males and a median age of 63 years (p&lt;0.001 vs aspirin users; p=0.012 vs NSAID users). POLYPS: ASPIRIN vs CONTROLS. Polyps&gt;5 mm were found in 21 (19%) subjects taking aspirin vs 99 (27%) controls [odds ratio, OR, 0.57; 95% confidence intervals, CI, (0.33–0.98); p=0.042]. Polyps &gt;5 mm or cancer were found in 24 (21%) aspirin users vs 118 (32%) controls [OR, 0.50; 95% CI (0.30.0.84); p=0.009]. POLYPS: NSAIDs vs CONTROLS. Polyps &gt;5 mm were found in 5 (11%) subjects taking NSAIDs vs 99 (27%) controls [OR, 0.36; 95% CI (0.14–0.86); p=0.036]. Polyps &gt;5 mm or cancer were found in 6 (13%) NSAID users vs 118 (32%) controls [OR, 0.35; 95% CI (0.14–0.86); p=0.022]. <h3>Conclusions</h3> (1) In this bowel cancer screening program, subjects taking low-dose aspirin were older while those taking NSAIDs were younger than controls not using either of these agents. (2) After adjusting the odds ratios for age and sex, the use of aspirin or NSAIDs was associated with lower prevalence of dysplastic colonic polyps or cancers. These results provide further evidence for the potential use of aspirin or NSAIDs for bowel cancer chemoprevention.
Geographic origin of the family as a determinant of serum levels of lipids in Finnish children.
Authors: EPesonen, JViikari, H KAkerblom, LRäsänen, KLouhivuori, SSarna
Journal: Circulation (1986)

Children in the eastern part of Finland have higher serum total and low-density lipoprotein (LDL) cholesterol levels than children in the western part of the country. This is consonant with the high mortality rate for coronary heart disease in eastern Finland. Eastern and western Finns are assumed to have different geographic origins; because of this we divided into groups 630 newborns and 3554 children and adolescents according to their grandparents' birthplace, which, in Finland, reflect the origins of the children. No differences in serum lipid levels were found in the newborns but in the 3- to 18-year-old children the differences in mean serum total and LDL cholesterol levels were accentuated by this division. Boys with grandparents from the extreme eastern part and those with grandparents from the western part of the country showed the greatest differences. Prepubescent boys 3 to 12 years old living in the west but with grandparents from the east had total and LDL cholesterol levels similar to those ...
Exosomes and extracellular vesicles: Rethinking the essential values in cancer biology
Authors: Akira Yokoi, Takahiro Ochiya
Journal: Seminars in Cancer Biology (2021)

Extracellular vesicles (EVs) such as exosomes are released by all living cells and contain diverse bioactive molecules, including nucleic acids, proteins, lipids, and metabolites. Accumulating evidence of EV-related functions has revealed that these tiny vesicles can mediate specific cell-to-cell communication. Within the tumor microenvironment, diverse cells are actively interacting with their surroundings via EVs facilitating tumor malignancy by regulating malignant cascades including angiogenesis, immune modulation, and metastasis. This review summarizes the recent studies of fundamental understandings of EVs from the aspect of EV heterogeneity and highlights the role of EVs in the various steps from oncogenic to metastatic processes. The recognition of EV subtypes is necessary to identify which pathways can be affected by EVs and which subtypes can be targeted in therapeutic approaches or liquid biopsies.
Identification of functional angiotensin II receptors on rat cardiac fibroblasts.
Authors: F JVillarreal, N NKim, G DUngab, M PPrintz, W HDillmann
Journal: Circulation (1993)

BACKGROUNDCardiac hypertrophy results in an increased deposition of the extracellular matrix (ECM) proteins fibronectin and collagen. Recent evidence indicates that angiotensin II (Ang II) might have an important role in the development of myocardial fibrosis accompanying cardiac hypertrophy. We sought to determine whether fibroblasts of cardiac origin (isolated from neonatal and adult animals) express receptors for Ang II and to examine the ability of this peptide to regulate fibronectin and collagen gene expression in a cultured adult cardiac fibroblast cell preparation.METHODS AND RESULTSBinding of 125I-Ang II to both neonatal and adult cardiac fibroblasts in culture was specific, reversible, and saturable, with the receptor evenly distributed over the cell population. Competition binding experiments with receptor-specific antagonists indicate that Ang II receptors found on both fibroblast types were of the AT1 subtype. Analysis of mRNA levels for the AT1 receptor indicates that adult cardiac fibroblas...
Effects of regional alpha- and beta-blockade on resting and hyperemic coronary blood flow in conscious, unstressed humans.
Authors: J MHodgson, M DCohen, SSzentpetery, M DThames
Journal: Circulation (1989)

Our purpose was to determine if there are basal adrenergic influences on the coronary circulation in humans. We studied 56 patients with denervated hearts after cardiac transplantation and 19 normally innervated patients with angiographically normal coronary arteries. Coronary blood flow velocity was measured during cardiac catheterization with a subselective 3F intracoronary Doppler catheter. Heart rate was controlled by atrial pacing. Epicardial coronary artery diameter was measured by automated analysis of digital coronary angiograms. Coronary flow reserve was assessed by intracoronary papaverine hydrochloride (12 mg) injections. Regional sympathetic blockade was produced by intracoronary injections of phentolamine (3 mg, alpha) and propranolol (2 mg, beta) or metoprolol (3 mg, beta 1). After alpha-blockade, mean arterial pressure fell significantly (p less than 0.05) in both the denervated transplant (-5.8 +/- 1.5%) (mean +/- SEM) and normally innervated patients (-12.6 +/- 3.2%). Reductions in corona...
The deceptive aortic root.
Authors: MViamote, MCamacho, D RCahill, MViamonte, KMori
Journal: Circulation (1975)

Coronal, horizontal, and sagittal sections through the mid-line are excellent ways of depicting the anatomical position of the aortic root and for studying its topographical relationship to the surrounding vascular structures. Minimal radiographic abnormalities or no abnormalities at all may be present with an enlarged ascending portion of the thoracic aorta. Thus, frontal chest roentgenograms obtained with high kilovoltage, fluoroscopy and left anterior oblique projections should be utilized routinely for the evaluation of the ascending aorta. Calcification of the aortic valve and of the coronary arteries and the study of aortic valve prosthesis also demand a dynamic study and the use of complementary views, such as lateral and both oblique projections.
Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung
Authors: Rania G. Aly, Natasha Rekhtman, Xiaoyu Li, Yusuke Takahashi, Takashi Eguchi, Kay See Tan, Charles M. Rudin, Prasad S. Adusumilli, William D. Travis
Journal: Journal of Thoracic Oncology (2019)
Induction of myocardial insulin-like growth factor-I gene expression in left ventricular hypertrophy.
Authors: T JDonohue, L DDworkin, M NLango, KFliegner, R PLango, J ABenstein, W RSlater, V MCatanese
Journal: Circulation (1994)

BACKGROUNDLeft ventricular hypertrophy is a generalized adaptation to increased afterload, but the growth factors mediating this response have not been identified. To explore whether the hypertrophic response was associated with changes in local insulin-like growth factor-I (IGF-I) gene regulation, we examined the induction of the cardiac IGF-I gene in three models of systolic hypertension and resultant hypertrophy.METHODS AND RESULTSThe model systems were suprarenal aortic constriction, uninephrectomized spontaneously hypertensive rats (SHR), and uninephrectomized, deoxycorticosterone-treated, saline-fed rats (DOCA salt). Systolic blood pressure reached hypertensive levels at 3 to 4 weeks in all three systems. A differential increase in ventricular weight to body weight (hypertrophy) occurred at 3 weeks in the SHR and aortic constriction models and at 4 weeks in the DOCA salt model. Ventricular IGF-I mRNA was detected by solution hybridization/RNase protection assay. IGF-I mRNA levels increased in all th...
Variability of transient myocardial ischemia in ambulatory patients with coronary artery disease.
Authors: E GNabel, JBarry, M BRocco, SCampbell, KMead, TFenton, E JOrav, A PSelwyn
Journal: Circulation (1988)

Ambulatory electrocardiographic (ECG) monitoring of patients with chronic stable angina has demonstrated frequent and prolonged episodes of ischemic ST segment depression, but its clinical use requires an understanding of the components and extent of variability. Therefore, variations in the frequency and duration of episodes of ST segment depression were evaluated with ambulatory ECG recording at daily, weekly, and monthly intervals in 42 patients with chronic stable angina and known coronary artery disease. Data were analyzed with a nested analysis of variance design that yields estimates of variance components. From the estimates of variance components, power calculations and minimum significant percent reductions in frequency and duration of ischemia were derived. During 4,656 hours of ambulatory ECG monitoring, 1,262 episodes of ischemic ST segment depression were detected. The frequency of episodes was 6.3 +/- 0.45/24 hr (mean +/- SEM), and the duration of episodes was 18.3 +/- 2.8/24 hr. Because of...
Isometric relaxation of rat myocardium at end-systolic fiber length.
Authors: A WWiegner, S HBing
Journal: Circulation Research (1978)

In a   contraction (PSC), which loads the isolated muscle preparation in a manner which approximates that of the intact heart, isometric relaxation precedes isotonic relaxation and occurs at minimum (end-systolic) length. We studied the effects of inital muscle length, load, temperature, calcium, and isoproterenol on the isometric relaxation phase of physiologically sequenced contractions to define the determinants of the rate of isometric relaxation of rat left ventricular myocardium. At the baseline temperature (28 degrees C), relaxation was found to be nonexponential, and the maximum rate of decline of force (-dF/dtmax) was used to evaluate changes in relaxation. Three factors, shortening, end-systolic length, and total load, were examined as possible mechanical determinants of -dF/dtmax. We found that -dF/dtmax is linearly related to end-systolic muscle length for lengths below 94% of Lmax; -dF/dtmax is also strongly related to total load for lightly loaded contractions, bu...
Evaluation of left ventricular function (ejection fraction and segmental wall motion) by single pass radioisotope angiography.
Authors: J AJengo, IMena, ABlaufuss, J MCriley
Journal: Circulation (1978)

Changes in ejection fraction (EF) and segmental wall motion (SWM) have been shown to be sensitive indicators of left ventricular (LV) function. This information is only obtainable by contrast angiography or gated blood pool scans. Gated studies assume a fixed geometry for the LV for EF determinations, are lengthy and limited primarily to the LAO projection. We correlated contrast and Tc-99m pertechnetate angiograms by singl pass radioisotope angiography (immediately preceding the contrast study) in 12 patients. EF was calculated from the LV time/activity curve and values ranged from .21 to .72. Angiographic correlation yielded r = 0.97. Regional LV wall motion was evaluated by dividing a summated cardiac cycle into 16 frames and dynamically and sequentially displaying these frames. Regional wall motion evaluation of four LV quadrants correlated well with angiography (r = 0.97). For quantitation these images were divided into four anterior and four inferior segments and the areas of respective segments wer...
Analysis of baroreflex control of heart rate in conscious dogs with pacing-induced heart failure.
Authors: J SChen, WWang, TBartholet, I HZucker
Journal: Circulation (1991)

The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin. BRS was significantly depressed in the heart failure state [nitroglycerin slope, 5.0 +/- 2.7 (mean +/- SD) versus 16.6 +/- 5.1 msec/mm Hg, p less than 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 msec/mm Hg, p less than 0.005]. There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes. After beta 1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p less than 0.001). Atropine significantly increased resting heart rate more in the...
Inhibition of coronary atherosclerosis by propranolol in behaviorally predisposed monkeys fed an atherogenic diet.
Authors: J RKaplan, S BManuck, M RAdams, K WWeingand, T BClarkson
Journal: Circulation (1987)

We studied the effect of propranolol on the diet-induced coronary artery atherosclerosis (CAA) in 30 adult male cynomolgus monkeys living in social groupings of five animals each. Animals in the treated segment (n = 15) consumed propranolol, which was mixed into an atherogenic diet. Animals in the  group (n = 15) consumed only the atherogenic diet. Finally, the social groupings were subjected to disruption through monthly redistribution of monkeys among the groups within each treatment segment. The experiment lasted 26 months, following which all animals underwent autopsy during which the coronary arteries were evaluated for atherosclerosis. Regarding atherosclerosis, we observed a significant interaction between social status and experimental condition (p less than .03). Socially dominant animals had (as in previous studies) significantly exacerbated CAA, but only in the untreated segment; the effect of social dominance on CAA was abolished by long-term administration of propranolol. The ant...
Acidemia and hypernatremia enhance postischemic recovery of excitation-contraction coupling.
Authors: KHarada, AFranklin, R GJohnson, WGrossman, J PMorgan
Journal: Circulation Research (1994)

The purpose of the present study was to determine whether Na(+)-H+ and Na(+)-Ca2+ exchanges modulate postischemic recovery of excitation-contraction coupling. Experiments were performed in 43 isolated isovolumic dog hearts perfused with blood (pH 7.40, 141 mmol/L Na+, 34 degrees C, paced at 2 Hz). A 3 x 3-mm region at the left ventricular (LV) apex was loaded with aequorin for monitoring [Ca2+]i simultaneously with LV pressure. No-flow ischemia for 2 to 3 minutes was followed by 20 minutes of aerobic reperfusion with (1) unmodified control blood (141 mmol/L Na+, pH 7.40), (2) acidemic blood (141 mmol/L Na+, pH 6.60, at 0 to 3 minutes of reperfusion), (3) hypernatremic blood (149 or 157 mmol/L Na+, pH 7.40, at 0 to 20 minutes of reperfusion), or (4) hyperosmotic blood (141 mmol/L Na+ + 30 mmol/L mannitol, pH 7.40, at 0 to 20 minutes of reperfusion). Reperfusion with unmodified control blood was immediately followed by an increase in [Ca2+]i and LV systolic and diastolic pressure that persisted for 2 to 3 m...
Restoration by insulin of impaired prostaglandin E1/I2 receptor activity of platelets in acute ischemic heart disease.
Authors: N NKahn, H SMueller, A KSinha
Journal: Circulation Research (1991)

Treatment of normal platelet-rich plasma with a physiological amount of insulin (100 microunits/ml, optimum concentration) for 3 hours at 23 degrees C stimulated the binding of prostaglandin E1 by more than twofold (3,940 +/- 250 sites/10(8) platelets) compared with the nontreated, control platelet-rich plasma (1,590 +/- 265 sites/10(8) platelets). After platelet-rich plasma from patients with acute ischemic heart disease (n = 43), whose platelets showed impaired prostaglandin E1/I2 receptor activity (850 +/- 100 sites/10(8) platelets), was incubated with insulin (optimum amounts varied from 100 to 200 microunits/ml), the binding of the prostanoid was restored to normal levels (1,790 +/- 140 sites/10(8) platelets) in 75% of the cases. Twenty-five percent of the patients did not respond to the stimulatory effect of insulin. The increased binding of the prostanoid to the insulin-treated platelets also resulted in increased cyclic AMP levels both in normal subjects (44.14 +/- 3.1 pmol/10(8) [insulin-treated]...
Epicardial mapping of ventricular defibrillation with monophasic and biphasic shocks in dogs.
Authors: XZhou, J PDaubert, P DWolf, W MSmith, R EIdeker
Journal: Circulation Research (1993)

To study the mechanism of defibrillation and the reason for the increased defibrillation efficacy of biphasic waveforms, the potential gradient in a 32 x 30-mm region of the right ventricle in 15 dogs was progressively lowered in four steps while a strong potential gradient field was maintained throughout the rest of the ventricular myocardium. The volume of right ventricle beneath the plaque was 10 +/- 2% of the total ventricular mass. A 10-msec monophasic (eight dogs) or 5/5-msec biphasic (seven dogs) truncated exponential shock 30% above the defibrillation threshold voltage was given via electrodes on the left ventricular apex and right atrium to create the strong potential gradient field. Simultaneously, a weaker shock with the same waveform but opposite polarity was given via mesh electrodes on either side of the small right ventricular region to cancel part of the potential difference in the region and to create one of the four levels of potential gradient fields. Shock potentials and activations we...