tbuckley/cabot-search huggingface dataset:
A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.
Authors: A GBostom, D RGagnon, L ACupples, P WWilson, J LJenner, J MOrdovas, E JSchaefer, W PCastelli
Journal: Circulation (1994)

BACKGROUNDSinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women.METHODS AND RESULTSFrom 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band pr...
Postoperative changes in aortocoronary saphenous vein grafts revisited: angiographic studies at two weeks and at one year in two series of consecutive patients.
Authors: LCampeau, DCrochet, JLespérance, M GBourassa, C MGrondin
Journal: Circulation (1975)

Comparison of aortocoronary saphenous vein graft status at two weeks and at one year was made in two series of patients. The early postoperative evaluation includes 122 patients of the first 138 operated in our institution (182 grafts) and 83 subjects from a second series of 100 patients operated after modifications of surgical techniques (184 grafts). The one-year follow-up study was obtained in 105 patients of the first series (154 grafts) and in 67 of the second (152 grafts). The patency rate at two weeks was not significantly different between the two groups: 86.3% vx. 91.8%. A marked decrease of steonses noted early at anastomotic sites was observed: 15% to 5.5% (P less than 0.025). The patency rate at one year improved from 67% to 85,5% (P less than 0.0005). Grafts having flows at operation of at least 50 ml/min had patency rates of 90% in both series. The patency in grafts with initial flows below 50 ml/min increased from 28% to 73% (P less than 0.005). The incidence of late localized graft stenose...
End-systolic pressure as a balance between opposing effects of ejection.
Authors: W CHunter
Journal: Circulation Research (1989)

Ejection has previously been thought to exert only negative effects on end-systolic left ventricular pressure, via mechanisms like shortening deactivation and the force-velocity relation. Whether ejection also exerted a positive influence on pressure generation was tested by comparing two successive beats: 1) the last beat of steady-state ejection versus 2) a totally isovolumic contraction at the end-systolic volume. In 12 isolated, blood-perfused canine hearts loaded with a simulated arterial system, ejecting end-systolic pressure exceeded isovolumic pressure by approximately 10 mm Hg when ejection fraction was 0.3. With both higher and lower ejection fractions, the excess of ejecting end-systolic pressure was smaller; beyond an ejection fraction of roughly 0.5, the trend reversed so that ejecting end-systolic pressure fell below isovolumic pressure. The maximum excess in ejecting end-systolic pressure was quite variable (1-17 mm Hg), but the pattern of its variation with ejection fraction was consistent...
Parasympathetic effects on in vivo rat heart can be regulated through an alpha 1-adrenergic receptor.
Authors: P AMcGrattan, J HBrown, O MBrown
Journal: Circulation Research (1987)

A prejunctional mechanism involving an alpha 1-adrenergic receptor may exert control on the release of acetylcholine from parasympathetic nerve endings in the heart. To test this hypothesis in vivo, rats were prepared for electrical stimulation of the vagus nerves. Blood pressures and heart rates were monitored, and the animals were treated with alpha-agonists and alpha-antagonists. The alpha 1-selective agonist phenylephrine significantly attenuated vagally induced bradycardia in a dose-dependent fashion (ED50 = 19 micrograms/kg). This is consistent with the hypothesis that there is alpha-adrenergic inhibition of ACh release. In contrast, the alpha 2-selective agonist, BHT-920, caused no change in heart rate during vagal stimulation. The effects of phenylephrine to raise heart rate and blood pressure during vagal stimulation were blocked by the alpha 1-selective antagonist prazosin (ID50 approximately 1 microgram/kg) but not by the alpha 2-selective antagonists yohimbine and rauwolscine. This further sup...
The Endocrine System
Authors: E. Hindle, M. Calzada-Naucaudie, I. Keller, Serge Askienazy
Journal: Clinical Nuclear Medicine (2008)

Although sonography (US) and cytology (fine-needle aspiration, FNA) play the principal role in the diagnosis of thyroid nodules, thyroid scintigraphy remains an important tool for guiding clinical decisions in thyroid diseases. Thyroid scintigraphy is so used in the diagnosis of the cause of a patient's hyperthyroidism (Graves' disease, thyroid autonomy, subacute, silent and post-partum thyroiditis, etc.), in the evaluation of selected patients with thyroid nodules and in the identification of normal and ectopic thyroid tissue (neonatal hypothyroidism).
Vascular angiotensin II receptors and sodium balance in rats. Role of kidneys and vascular renin activity.
Authors: J DSwales, J DTange, HThurston
Journal: Circulation Research (1975)

The relationship between the vascular response. to angiotensin II and sodium balance was studied by measuring the volume of specific antiserum needed to block the pressor response to a standard dose of angiotensin II in rats. In normal rats, sodium depletion reduced the volume of antiserum required to prevent a pressor response to 50 ng of angiotensin II from 0.32 to 0.22 ml; sodium loading increased the volume required to 0.65 ml. After bilateral nephrectomy, there was a progressive increase in the antibody requirement to a maximum of 0.63 ml at 6 hours. At this stage, there was no change in the blocking requirement with sodium depletion by either pretreatment with a low-salt diet (0.60 ml) or peritoneal dialysis (0.62 ml). The pressor response to a 50-ng bolus of angiotensin II was closely correlated with the antibody requirement in all experiments (r equals plus 0.93). These observations indicate that sodium-induced changes in the vascular response to angiotensin II require the presence of kidney tissu...
Remodeling of myocyte dimensions in hypertrophic and atrophic rat hearts.
Authors: S ECampbell, BKorecky, KRakusan
Journal: Circulation Research (1991)

Changes in hemodynamic load cause alterations in cardiac myocyte size, with regional variations in myocyte size distribution possible within the ventricular wall. We studied regional changes in cellular dimensions and their distribution in two models of cardiac hypertrophy and in cardiac atrophy in the rat. Combined volume-pressure overload was produced by 3,3',5-triiodo-L-thyronine (T3) treatment; atrophy was produced by heterotopic isotransplantation. Our previous data from long-term pressure overload after aortic constriction were used for comparison. Isolated ventricular myocytes were obtained after in vitro coronary perfusion with collagenase. Cell volume and its distribution were determined; cell length was directly measured by image analysis, and cross-sectional area was estimated from the cell volume/cell length ratio, assuming a cylindrical model. Myocyte hypertrophy resulting from hyperthyroidism and aortic constriction was primarily due to increased cross-sectional area. In both cases, the rela...
Subxiphoid two-dimensional imaging of the interatrial septum in infants and neonates with congenital heart disease.
Authors: F ZBierman, R GWilliams
Journal: Circulation (1979)

The interatrial septum (IAS) was studied by subxiphoid two-dimensional echocardiography (S2DE) in 88 infants under 12 months of age who weighed 1.2-9.1 kg. The IAS was adequately displayed in 87 of 88 patients. The morphology, presence and localization of defects in the IAS were evaluated by S2DE and retrospectively related to the findings at cardiac catheterization. In seven patients with no interatrial communication at cardiac catheterization, the IAS was straight, with an area of central thinning corresponding to the veil-like cover of the septum primum over the foramen ovale. The morphology of the IAS with a stretched, patent foramen ovale (56 patients) indicated the coexistence of a right or left ventricular volume or pressure overload, and was readily distinguishable from the IAS with a secundum type communication (13 patients). In patients with a stretched, patent foramen ovale and left ventricular overload lesions, the IAS was a nearly homogenous, curvilinear structure bowing into the right atrium...
Biochemical evidence of a chronic abnormality in platelet and vascular function in healthy individuals who smoke cigarettes.
Authors: JNowak, J JMurray, J AOates, G AFitzGerald
Journal: Circulation (1987)

Cigarette smoking is associated with increased mortality from cardiovascular disease that declines after cessation. This study extends the evidence regarding the effects of chronic smoking on platelets and the vessel wall in vivo. Excretion of a major urinary thromboxane metabolite, 2,3-dinor-thromboxane B2, is significantly (p less than .01) elevated in apparently healthy chronic smokers (20 cigarettes daily) compared with that in nonsmoking control subjects. This difference in excretion of 2,3-dinor-thromboxane B2 was abolished by the administration of 20 mg aspirin twice daily, a dose shown to selectively inhibit platelet cyclooxygenase. After aspirin, the return of the excretion of 2,3-dinor-thromboxane B2 to pretreatment levels paralleled the recovery of platelet cyclooxygenase. These findings indicate that excessive thromboxane A2 generation in chronic smokers predominantly derives from platelets. The urinary excretion of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1 alpha also is in...
Heterotopic Gastric Mucosa of the Rectum
Authors: P. De Angelis, A. Trecca, P. Francalanci, F. Torroni, G. Federici di Abriola, B. Papadatou, G. Ciofetta, L. Dall’Oglio
Journal: Endoscopy (2004)

Heterotopic gastric mucosa (HGM), which results from embryonic tissue displacement, can be found throughout the length of the gastrointestinal tract. Heterotopic gastric mucosa in the rectum is uncommon, and few cases have been described in children [1] [2] [3].
Effects of endothelial denudation and cholesterol feeding on in vivo transport of albumin, glucose, and water across rabbit carotid artery.
Authors: A VChobanian, J OMenzoian, JShipman, KHeath, C CHaudenschild
Journal: Circulation Research (1983)

An in vivo system for studying arterial transport was developed which utilized the rabbit carotid artery perfused in vivo with Dulbecco's modified Eagle's medium containing 125I-labeled albumin, [3H]-3-methyl-d-glucose, or tritiated water. The appearance of labeled materials in jugular venous blood was measured serially over 4 hours. Vascular integrity was assessed by scanning electron and transmission microscopy. Maintenance of endothelial integrity appeared dependent on perfusion with nutrient tissue culture medium, use of papaverine to inhibit arterial spasm, and circulation of the medium under pressure. Acute endothelial denudation with a balloon catheter induced an approximate 10-fold increase in plasma concentration of labeled albumin and a 3-fold rise in plasma [3H]-3-methyl-d-glucose activity, compared with results in animals with intact endothelium. Increased appearance of tritiated water in venous blood was also observed in the rabbits with denuded endothelium, although the relative rise was les...
The relationships between alcoholic beverage use and other traits to blood pressure: a new Kaiser Permanente study.
Authors: A LKlatsky, G DFriedman, M AArmstrong
Journal: Circulation (1986)

In a new study controlled for many factors, we reconfirmed the relationship of higher blood pressure to alcohol use. This relationship was slightly stronger in men, whites, and persons 55 years of age or older. A slight increase in blood pressure appeared in men who drank one to two drinks daily, and a continuous increase occurred at all higher drinking levels among white men who had constant drinking habits. Among women, an increase occurred only at three or more drinks daily. The data suggest complete regression, beginning within days, of alcohol-associated hypertension upon abstinence. Blood pressure showed minor differences with beverage preference: those who preferred liquor had higher adjusted mean blood pressure than those preferring wine or beer. The results of this study contribute to the likelihood that the alcohol-blood pressure association is causal. Smoking, coffee use, and tea use showed no association with higher blood pressure. Systolic pressure showed a positive relationship to total seru...
Endogenous biosynthesis of prostacyclin during cardiac catheterization and angiography in man.
Authors: LRoy, H RKnapp, R MRobertson, G AFitzGerald
Journal: Circulation (1985)

The potent platelet inhibitory and vasodilator properties of prostacyclin suggest that levels of this substance may be of relevance to drug action and pathologic processes in the coronary vascular bed. Attempts to estimate the coronary secretion rate of prostacyclin have relied on measurements of metabolites obtained via cardiac catheter, usually as an adjunct to coronary angiography. To test the hypothesis that such procedures might themselves perturb endogenous biosynthesis of prostacyclin we used mass spectrometry to measure plasma levels of 6-keto-prostaglandin (PG) F1 alpha across the coronary vascular bed, as well as to assess the excretion of a major urinary metabolite, 2,3-dinor-6-keto-PGF1 alpha (PGI-M), in patients undergoing cardiac catheterization. PGI-M excretion increased variably from a median 100 to 205 pg/mg creatinine (p less than .01) during catheterization with angiography and remained elevated 2 to 4 hr after initiation of the procedure. However, cardiac catheterization without angiog...
Fluorescence-guided laser-assisted balloon angioplasty in patients with femoropopliteal occlusions.
Authors: M BLeon, YAlmagor, A LBartorelli, L GPrevosti, P STeirstein, RChang, D LMiller, P DSmith, R FBonner
Journal: Circulation (1990)

In 12 patients (aged 64 +/- 10 years) with femoropopliteal occlusions (1-27 cm; average, 8.4 cm length) that could not be recanalized by standard guidewire-balloon angioplasty techniques, percutaneous laser-assisted balloon angioplasty was performed by use of a new fluorescence-guided dual-laser system. Plaque detection by 325-nm laser-excited fluorescence spectroscopy provided real-time feedback control to a 480-nm pulsed dye laser (2-microseconds pulses) for atheroma ablation. By means of a common 200-microns optical fiber, after diagnostic fluorescence sensing, computer algorithms directed a fire or no-fire signal (5 Hz) to the treatment laser for selective plaque removal. Laser recanalization (15-50 mJ/pulse) was successful in 10 of 12 patients; this procedure was followed by definitive balloon angioplasty in seven of 12 patients with increased ankle/arm indexes (from 0.60 +/- 0.12 at baseline to 0.84 +/- 0.11 after treatment, p = 0.0043). In laser and balloon angioplasty failures, all femoropopliteal...
Lack of involvement of thromboxane A2 in postischemic recovery of stunned canine myocardium.
Authors: N EFarber, G MPieper, G JGross
Journal: Circulation (1988)

Modification of the thromboxane: prostacyclin ratio alters the severity of reperfusion arrhythmias and postischemic damage in long-term, irreversibly injured myocardium. In this study, the effects of the thromboxane synthetase inhibitor dazmegrel and the thromboxane receptor antagonist BM 13.505 on myocardial postischemic functional recovery and preservation of tissue adenine nucleotides was examined after a 15-minute episode of ischemia followed by 3 hours of reperfusion (myocardial stunning). Dazmegrel (3 or 8 mg/kg) or BM 13.505 (10 mg/kg) was given 15 minutes before coronary occlusion and compared with a control group in barbital-anesthetized dogs. Regional segment shortening (percent segment shortening, sonomicrometry), regional myocardial blood flow (microspheres), and coronary venous eicosanoid and high-energy phosphate levels (biopsies after 3 hours of reperfusion) were measured. Areas at risk, regional myocardial blood flow, and regional segment shortening during coronary occlusion were similar i...
Mechanisms of bradycardia-induced ventricular arrhythmias in myocardial ischemia and infarction.
Authors: B JScherlag, GKabell, LHarrison, RLazzara
Journal: Circulation (1982)

Experimental and clinical cases have been described in which bradycardia, i.e., heart rates below 60 beats/min or slowing of the heart rate, resulted in lethal ventricular arrhythmias during various stages of myocardial ischemia and infarction. The present study was designed to determine the relationship of lethal ventricular arrhythmias and slow heart rates. In 18 dogs anesthetized with sodium pentobarbital, the left anterior descending (LAD) coronary artery was ligated. Standard ECGs, His bundle electrograms and composite electrograms from intramural and epicardial areas in ischemic and normal zones were recorded during the first 3 hours of ischemia. Vagosympathetic trunk stimulation caused varying degrees of slowing and bradycardia. Of the 18 dogs, slowing of the heart rate or marked bradycardia induced ventricular ectopic beats coupled to the sinus beats in two, sustained ventricular tachycardia in two, and ventricular fibrillation in two. In another group of six dogs studied 17-25 days after LAD liga...
SERCA2a stimulation by istaroxime improves intracellular Ca2+ handling and diastolic dysfunction in a model of diabetic cardiomyopathy
Authors: Eleonora Torre, Martina Arici, Alessandra Maria Lodrini, Mara Ferrandi, Paolo Barassi, Shih-Che Hsu, Gwo-Jyh Chang, Elisabetta Boz, Emanuela Sala, Sara Vagni, Claudia Altomare, Gaspare Mostacciuolo, Claudio Bussadori, Patrizia Ferrari, Giuseppe Bianchi, Marcella Rocchetti
Journal: Cardiovascular Research (2021)

Diabetic cardiomyopathy is a multifactorial disease characterized by an early onset of diastolic dysfunction (DD) that precedes the development of systolic impairment. Mechanisms that can restore cardiac relaxation improving intracellular Ca2+ dynamics represent a promising therapeutic approach for cardiovascular diseases associated to DD. Istaroxime has the dual properties to accelerate Ca2+ uptake into sarcoplasmic reticulum (SR) through the SR Ca2+ pump (SERCA2a) stimulation and to inhibit Na+/K+ ATPase (NKA). This project aims to characterize istaroxime effects at a concentration (100 nmol/L) marginally affecting NKA, in order to highlight its effects dependent on the stimulation of SERCA2a in an animal model of mild diabetes.Streptozotocin (STZ) treated diabetic rats were studied at 9 weeks after STZ injection in comparison to controls (CTR). Istaroxime effects were evaluated in vivo and in left ventricular (LV) preparations. STZ animals showed (i) marked DD not associated to cardiac fibrosis, (ii) LV mass reduction associated to reduced LV cell dimension and T-tubules loss, (iii) reduced LV SERCA2 protein level and activity and (iv) slower SR Ca2+ uptake rate, (v) LV action potential (AP) prolongation and increased short-term variability (STV) of AP duration, (vi) increased diastolic Ca2+, and (vii) unaltered SR Ca2+ content and stability in intact cells. Acute istaroxime infusion (0.11 mg/kg/min for 15 min) reduced DD in STZ rats. Accordingly, in STZ myocytes istaroxime (100 nmol/L) stimulated SERCA2a activity and blunted STZ-induced abnormalities in LV Ca2+ dynamics. In CTR myocytes, istaroxime increased diastolic Ca2+ level due to NKA blockade albeit minimal, while its effects on SERCA2a were almost absent.SERCA2a stimulation by istaroxime improved STZ-induced DD and intracellular Ca2+ handling anomalies. Thus, SERCA2a stimulation can be considered a promising therapeutic approach for DD treatment.
Atractylenolide I enhances responsiveness to immune checkpoint blockade therapy by activating tumor antigen presentation
Authors: Hanchen Xu, Kevin Van der Jeught, Zhuolong Zhou, Lu Zhang, Tao Yu, Yifan Sun, Yujing Li, Changlin Wan, Ka Man So, Degang Liu, Michael Frieden, Yuanzhang Fang, Amber L. Mosley, Xiaoming He, Xinna Zhang, George E. Sandusky, Yunlong Liu, Samy O. Meroueh, Chi Zhang, Aruna B. Wijeratne, Cheng Huang, Guang Ji, Xiongbin Lu
Journal: Journal of Clinical Investigation (2021)

One of the primary mechanisms of tumor cell immune evasion is the loss of antigenicity, which arises due to lack of immunogenic tumor antigens as well as dysregulation of the antigen processing machinery. In a screen for small-molecule compounds from herbal medicine that potentiate T cell-mediated cytotoxicity, we identified atractylenolide I (ATT-I), which substantially promotes tumor antigen presentation of both human and mouse colorectal cancer (CRC) cells and thereby enhances the cytotoxic response of CD8+ T cells. Cellular thermal shift assay (CETSA) with multiplexed quantitative mass spectrometry identified the proteasome 26S subunit non-ATPase 4 (PSMD4), an essential component of the immunoproteasome complex, as a primary target protein of ATT-I. Binding of ATT-I with PSMD4 augments the antigen-processing activity of immunoproteasome, leading to enhanced MHC-I-mediated antigen presentation on cancer cells. In syngeneic mouse CRC models and human patient-derived CRC organoid models, ATT-I treatment promotes the cytotoxicity of CD8+ T cells and thus profoundly enhances the efficacy of immune checkpoint blockade therapy. Collectively, we show here that targeting the function of immunoproteasome with ATT-I promotes tumor antigen presentation and empowers T cell cytotoxicity, thus elevating the tumor response to immunotherapy.
Composition of the Sepsis Definitions Task Force—Reply
Authors: Clifford S. Deutschman, Mervyn Singer
Journal: JAMA (2016)

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