tbuckley/cabot-search huggingface dataset:
Regular Aerobic Exercise Augments Endothelium-Dependent Vascular Relaxation in Normotensive As Well As Hypertensive Subjects
Authors: YukihitoHigashi, ShotaSasaki, SatoshiKurisu, AtsunoriYoshimizu, NobuoSasaki, HideoMatsuura, GoroKajiyama, TetsuyaOshima
Journal: Circulation (1999)

Background—Several nonpharmacological interventions, including exercise, are recommended in primary prevention of hypertension and other cardiovascular diseases in which the pathogenetic role of endothelial dysfunction has been suggested. We studied the effects of long-term aerobic exercise on endothelial function in patients with essential hypertension. Methods and Results—The forearm blood flow was measured by strain-gauge plethysmography. The responses of forearm vasculature to acetylcholine were smaller in the hypertensive patients than in the normotensive subjects. There was no significant difference in forearm vascular responses to isosorbide dinitrate in the normotensive and hypertensive subjects. We evaluated the effects of physical exercise for 12 weeks on forearm hemodynamics in untreated patients with mild essential hypertension who were divided randomly into an exercise group (n=10) and a control group (n=7). After 12 weeks, the forearm blood flow response to acetylcholine increased significan...
Thrombosis in Connection with Serum Lipidic Changes in the Rat
Authors: SergeRenaud, ClaudeAllard
Journal: Circulation Research (1962)

Addition of either propylthiouracil or cholic acid to a natural diet (Purina Laboratory Chow) enriched in certain lipids resulted in hypercholesteremia and hyperlipemia of about the same amplitude. However, only cholic acid could induce a high incidence of thrombosis and cardiac infarct and a regular decrease in the percentage of serum alphalipoproteins with an electrophoretic pattern similar to that found in essential hyperlipemia or in certain nephrotic syndromes associated with thrombosis. In the rat, the thrombi, located in the arterioles and the capillaries of the heart and other organs, presented a histological picture that resembled thrombotic-thrombocytopenic-purpura rather than coronary disease. This thrombotic phenomenon was preceded by an acute increase in serum cholesterol and total lipids and was accompanied by the production of a large quantity of macrophages, with a foamy appearance, in the lung and the spleen. If propylthiouracil was added to this thrombogenic diet, the survival time of th...
Abstract 18849: Blood Pressure and Excess Cardiovascular Events in Middle-aged Adults
Authors: Kunal N Karmali, Hongyan Ning, Donald M Lloyd-Jones
Journal: Circulation (2014)

Introduction: Blood pressure (BP) is continuously associated with atherosclerotic cardiovascular disease (ASCVD) risk, even when BP is at goal levels. Objectives: In this study, we sought to examine whether individuals at goal BP levels, who nonetheless experience ASCVD events, can be identified using multivariable risk assessment. Methods: We stratified participants (45-64 years) from the Framingham Offspring Study (exams 4-6) and Atherosclerosis Risk in Communities Study (exams 1-4) based on systolic BP levels (<120, 120-129, 130-139, 140-149, 150-159, ≥160 mm Hg). We calculated risk of an incident ASCVD event over 10 years using Cox models. We determined the number of excess ASCVD events in each BP stratum by calculating the difference between observed and expected number of events (with the ASCVD rate in SBP < 120 group used as referent). We estimated 10-year ASCVD risk at baseline for each participant using the 2013 ACC/AHA Pooled Cohort risk equations. Results: There were 14,985 participants (80% wh...
Abstract 4705: The novel oncolytic peptide, DTT-304, induces regression of colorectal cancer tumors in vivo
Authors: Karianne G. Fleten, Johannes J. Eksteen, Brynjar Mauseth, Ketil Camilio, Øystein Rekdal, Meng Yu Wang, Gunhild M. Mælandsmo, Kjersti Flatmark
Journal: Cancer Research (2018)

Abstract Colorectal cancer (CRC) is the third most common cancer in the world, and approximately 50% of the patients develop liver metastasis, which is a major cause of disease mortality. New drugs and treatment options are therefore necessary to improve the survival of these patients. Lately, different types of immunotherapy, such as check point inhibitors, have shown great promise in the treatment of metastatic cancer, although for most patients with CRC the efficacy has been restricted to cases with microsatellite instable disease. Another novel immunotherapeutic strategy is oncolytic immunotherapy, which has been shown to cause immunogenic cancer cell death. Following cancer cell lysis, damage associated molecular patterns (DAMPs) are released, which are recognized by immune cell receptors. Pro-inflammatory responses will then be triggered to induce release of tumor specific antigens that are presented to the immune system, leading to tumor-specific immune responses. In the present study, we have investigated the efficacy of a novel oncolytic peptide, DTT-304, using two mouse models. Subcutaneous tumors were established in Balb c mice using the cell line CT26 and in C57Bl6 mice using the cell line MC38, both murine CRC cell lines. In both models, intra-tumoral injection of the peptide induced tumor necrosis and complete regression a few days after initiation of treatment, thus showing the potential of this peptide for use in colorectal cancer. In ongoing experiments we are investigating if the peptide has the potential to induce long lasting protective tumor-specific immune responses by re-challenging previously treated mice with the same cell line in a liver metastasis model. In addition, the possibility of treating liver tumors by direct peptide injection will be investigated. Citation Format: Karianne G. Fleten, Johannes J. Eksteen, Brynjar Mauseth, Ketil Camilio, Øystein Rekdal, Meng Yu Wang, Gunhild M. Mælandsmo, Kjersti Flatmark. The novel oncolytic peptide, DTT-304, induces regression of colorectal cancer tumors in vivo [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4705.
Induced Adipocyte Cell-Sheet Ameliorates Cardiac Dysfunction in a Mouse Myocardial Infarction Model
Authors: YukikoImanishi, ShigeruMiyagawa, NorikazuMaeda, SatsukiFukushima, SatoruKitagawa-Sakakida, TakashiDaimon, AyumuHirata, TatsuyaShimizu, TeruoOkano, IichiroShimomura, YoshikiSawa
Journal: Circulation (2011)

Background—A drug delivery system that constitutively and effectively retains cardioprotective reagents in the targeted myocardium has long been sought to treat acute myocardial infarction. We hypothesized that a scaffold-free induced adipocyte cell-sheet (iACS), transplanted on the surface of the heart, might intramyocardially secrete multiple cardioprotective factors including adiponectin (APN), consequently attenuating functional deterioration after acute myocardial infarction. Methods and Results—Induced ACS were generated from adipose tissue–derived cells of wild-type (WT) mice (C57BL/6J), which secreted abundant APN, hepatocyte growth factor, and vascular endothelial growth factor in vitro. Transplanted iACS secreted APN into the myocardium of APN-knockout (KO) mice at 4 weeks. APN was also detected in the plasma of iACS-transplanted APN-KO mice at 3 months (245±113 pg/mL). After left anterior descending artery ligation, iACS, generated from either WT (n=40) or APN-KO (n=40) mice, were grafted onto ...
Acute Morphological Change in an Extracranial Carotid Artery Dissection on Transoral Carotid Ultrasonography
Authors: HikaruNagasawa, YasuhiroTomii, ChiakiYokota, KazunoriToyoda, HidekiMatsuoka, RiekoSuzuki, KazuoMinematsu
Journal: Circulation (2008)
Abstract 17264: β-Adrenergic Signaling Promotes Calcium Oscillations in Human Cardiac Progenitor Cells
Authors: NicolaAlesi, ChiaraMangiaracina, PolinaGoichberg, GiuliaBorghetti, SergioSignore, SilvanaBardelli, MarcoMoccetti, AndreaSorrentino, EwaWybieralska, LauraGraciotti, AntonioCannata, KanakoWaight, Sang HunShin, JungKim, AnnarosaLeri, PieroAnversa, TizianoMoccetti, MarcelloRota
Journal: Circulation (2014)

Catecholamines enhance cardiac function by activating effector molecules targeting Ca2+ handling proteins in myocytes, but the impact of these neurohumoral factors on the pool of resident primitive cells is poorly defined. The aim of this study was to establish whether catecholaminergic stimulation of human cardiac progenitor cells (hCPCs) promotes intracellular Ca2+ oscillations, critical events for cell cycle progression. For this purpose, c-kit-positive hCPCs were loaded with the Ca2+ indicator Fluo-4 and monitored by two-photon microscopy. After documenting that intracellular Ca2+ elevations in hCPCs are mediated by Ca2+ translocation from the endoplasmic reticulum to the cytoplasm via IP3 receptor channels, the effects of adrenergic receptor (AR) stimulation were tested. In Tyrode solution, Ca2+ spikes were observed in 12% of the cell population over a period of 33 minutes, and exposure to norepinephrine, agonist of α- and β-AR, increased the fraction of active cells to 26%. To dissect the contributi...
Abstract 15771: Genetic and Pharmacological Regulation of Circadian Energy Metabolism
Authors: Kwon Jeong, Baokun He, Seung-Hee Yoo, Zheng (Jake) Chen
Journal: Circulation (2015)

The circadian clock governs essential metabolic and physiological processes. For example, the sharp rise of blood pressure in the morning coincides with peak incidence rate for cardiovascular episodes such as heart attacks. The objective of the current studies is to elucidate novel mechanisms of genetic and pharmacological regulation of circadian clock and clock-related energy metabolism important for cardiovascular health. On the one hand, we investigated the functional mechanism of the Clockdelta19 mutation. Homozygous mutant mice (Clk/Clk) for this mutation have been shown to exhibit a wide spectrum of metabolic and cardiovascular disorders, correlated with a severe circadian misalignment or loss of rhythmicity in these mice. In comparison, Clockdelta19/+ heterozygous (Clk/+) mice showed sustained circadian rhythms, yet with significantly lengthened periodicity and dampened amplitude. We showed that Clk/+ mice exhibited improved glycemic control and resistance to circadian behavioral period lengthening under high-fat diet (HFD). Molecular analysis revealed that BMAL1 protein levels in Clk/+ mouse liver were upregulated compared with wild-type (WT) mice under HFD conditions. Mechanistic studies further demonstrated that CLOCKdelta19 stabilized BMAL1 proteins. Consistent with an important role of BMAL1 in glycemic control, enhanced activation of insulin signaling was observed in Clk/+ mice relative to WT. This study reveals an unforeseen plasticity of the circadian and metabolic networks, providing important insight into potential therapeutic intervention of clocks under disease conditions. On the other hand, we also identified small molecule modulators of the circadian clock. These small molecules, termed C lock amplitude- E nhancing small M olecules (CEMs), were able to enhance circadian amplitude of reporter rhythms in cardiomyocyte cells in vitro and improve energy expenditure and reduce cholesterol levels in vivo in a clock-dependent manner. Our studies together elucidate novel regulatory mechanisms for the circadian clock, and suggest novel therapeutic targets and drug candidates against clock-associated metabolic and cardiovascular diseases.
Abstract 17667: Local Atrophy of Parahippocampal Gyrus is Prominent in Heart Failure Patients Without Dementia
Authors: TomomiMeguro
Journal: Circulation (2014)

Introduction: The exacerbation of heart failure (HF) induces brain damage and the cognitive impairment that attenuates the effects of treatment. The medial lateral lobe of brain, including parahippocampal gyrus, is known to reduce its volume in patients with cognitive disorder especially in Alzheimer’s disease. The magnetic resonance imaging (MRI) scans identify morphological changes in the brains of patients with HF. Therefore, the Voxel-based morphometry (VBM) of three-dimensional brain MRI may contribute to predict the potential risk of mild cognitive impairment (MCI) of patients with HF. Hypothesis: The severity of local atrophy of parahippocampal gyrus, a potential risk of MCI, is prominent in heart failure patients without dementia. Methods: Ten HF patients (age 72+/-15 years, NYHA class II, EF43+/-15 %) and 9 control (age 76+/- 8 years) were enrolled. Patients with dementia were excluded from this study. Three dimensional T1 weighted sagittal images of whole brain were taken using 1.5T MRI. Image a...
Abstract 126: MYC-driven lymphomas suppress NK surveillance by blocking maturation of early NK cells
Authors: Line D. Heftdal, Srividya Swaminathan, Dean W. Felsher
Journal: Cancer Research (2018)

Abstract The MYC oncogene is commonly overexpressed in hematopoietic cancers. In a transgenic mouse model of MYC-induced T-cell lymphoma, we found that there was a systemic reduction in NK cell (CD3- NKp46High) numbers and activation in lymphoid organs such as spleen and bone marrow. MYC inactivation in lymphoma-bearing MYCON mice partially restored NK cell numbers and activation. Hence, the MYC oncogene appears to suppress NK cell-mediated immune surveillance of lymphomas. We evaluated whether reduction in mature and activated NK cells (CD3- NKp46High) in MYCON mice was due to increased death of NK cells in these mice when compared to normal and MYCOFF mice. Using flow cytometry, NK cells were measured in age matched spleens and bone marrows of normal (n = 8), MYCON (n = 8), and MYCOFF (n = 8) mice. Surprisingly, we observed a significant reduction in proportions of dead NK cells (NKp46+ PI+) in spleen and bone marrow of MYCON mice, in comparison to normal and MYCOFF cohorts. Hence, the reduction in activated NK cell numbers during MYC-driven lymphomagenesis does not occur because of increased death of NK cells. Next, we investigated whether MYC arrests early NK cell development in the bone marrow of lymphoma mice, leading to systemic NK suppression. NK cell lineage specification begins with CD122 expression, that is maintained throughout NK development starting at the precursor stage. NK precursors (NKP) transition to immature NK (iNK) cells by expressing the cytotoxicity marker NKp46. iNK cells leave the bone marrow to populate peripheral lymphoid organs. We measured NKP (CD122+ NKP46-), and iNK (CD122+ NKp46+) cells in bone marrow of normal (n = 8), MYCON (n = 8), and MYCOFF (n = 8) mice. We observed no significant changes in the percentages of NKP. However, the proportions of iNK cells were significantly reduced in MYCON mice, in comparison to MYCOFF and normal mice. Our results suggest that MYC may block transition from NKP to iNK stage during early NK cell development. The reduction of iNK cells in spleens of MYCON mice was concordant with the reduction of iNK cells in bone marrow from the same mice. We conclude that MYC-induced lymphomagenesis blocks early NK cell development, thereby suppressing NK-mediated immune surveillance. Citation Format: Line D. Heftdal, Srividya Swaminathan, Dean W. Felsher. MYC-driven lymphomas suppress NK surveillance by blocking maturation of early NK cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 126.
IgG3 regulates tissue-like memory B cells in HIV-infected individuals
Authors: Lela Kardava, Haewon Sohn, Christine Youn, James W. Austin, Wei Wang, Clarisa M. Buckner, J. Shawn Justement, Valerie A. Melson, Gwynne E. Roth, Marissa A. Hand, Kathleen R. Gittens, Richard W. Kwan, Michael C. Sneller, Yuxing Li, Tae-Wook Chun, Peter D. Sun, Susan K. Pierce, Susan Moir
Journal: Nature Immunology (2018)
Abstract 5266: Current smoking habit is a risk factor for poor surgical outcome of non-B, non-C hepatocellular carcinoma
Authors: Keita Kai, Hiroki Koga, Shinichi Aishima, Atsushi Kawaguchi, Koutaro Yamaji, Takao Ide, Junji Ueda, Hirokazu Noshiro
Journal: Cancer Research (2018)

Abstract Background: Many factors are recognized as risks for the development of hepatocellular carcinoma (HCC) in non-B non-C (NBNC) patients. Although cigarette smoking has been recognized as one of the risk factors for HCC, the surgical outcomes and clinicopathological characteristics according to smoking habits of NBNC-HCC patients are unclear. Methods: Consecutive cases of 83 NBNC-HCC patients who underwent curative surgical treatment for the primary lesion at Saga University Hospital were enrolled the study. The information about possibly carcinogenic factors such as alcohol abuse, diabetes mellitus, obesity and smoking habit were collected from medical records. Smoking habits were subcategorized as never, ex- and current smoker at the time of surgery. The diagnosis of non-alcoholic steatohepatitis (NASH) was based on both clinical information and pathological confirmation. Results: Alcohol abuse, diabetes mellitus, obesity and NASH had no significant effect on the surgical outcomes. Current smoking status was strongly correlated with both overall survival (p=0.0058) and disease-specific survival (p=0.0105) by multivariate analyses. Subset analyses revealed that current smokers were significantly younger at the time of surgery (p=0.0002) and more likely to abuse alcohol (p=0.0188) and to have multiple tumors (p=0.023). Conclusion: Current smoking habit at the time of surgery is a risk factor for poor long-term survival in NBNC-HCC patients. Current smokers tend to have multiple HCCs at a younger age than other patients. Citation Format: Keita Kai, Hiroki Koga, Shinichi Aishima, Atsushi Kawaguchi, Koutaro Yamaji, Takao Ide, Junji Ueda, Hirokazu Noshiro. Current smoking habit is a risk factor for poor surgical outcome of non-B, non-C hepatocellular carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5266.
Novel Mechanism for Brugada Syndrome
Authors: GhayathBaroudi, ValeriePouliot, IsabelleDenjoy, PascaleGuicheney, AlvinShrier, MohamedChahine
Journal: Circulation Research (2001)

Abstract—The SCN5A gene encodes the α subunit of the human heart sodium channel (hH1), which plays a critical role in cardiac excitability. Mutations of SCN5A underlie Brugada syndrome, an inherited disorder that leads to ventricular fibrillation and sudden death. This study describes changes in cellular localization and functional expression of hH1 in a naturally occurring SCN5A mutation (R1432G) reported for Brugada syndrome. Using patch-clamp experiments, we show that there is an abolition of functional hH1 expression in R1432G mutants expressed in human tsA201 cells but not in Xenopus oocytes. In tsA201 cells, a conservative positively charged mutant, R1432K, produced sodium currents with normal gating properties, whereas other mutations at this site abolished functional sodium channel expression. Immunofluorescent staining and confocal microscopy showed that the wild-type α subunit expressed in tsA201 cells was localized to the cell surface, whereas the R1432G mutant was colocalized with calnexin wit...
Occurrence and Prognostic Significance of Ventricular Arrhythmia Is Related to Pulmonary Function
Authors: GunnarEngström, PerWollmer, BoHedblad, SteenJuul-Möller, SvenValind, LarsJanzon
Journal: Circulation (2001)

Background—Reduced lung function has been associated with increased rates of myocardial infarction. Whether the occurrence and prognostic significance of ventricular arrhythmia is related to lung function is largely unknown. Methods and Results—We performed a population-based study of 68-year-old men without a history of stroke or myocardial infarction; 402 men participated. Mortality and coronary events (fatal or nonfatal) were studied in relation to ventricular arrhythmia during 24 hours, percentage of the predicted forced expiratory volume (FEV1%pred), vital capacity (VC%pred), and the FEV/VC ratio. During 14 years of follow-up, 181 men died and 87 experienced a coronary event. Occurrence of frequent or complex ventricular arrhythmia (Lown class 2 to 5) was significantly and inversely associated with FEV1%pred. Men with Lown class 2 to 5 and a low FEV1%pred (below median) had significantly higher mortality (71.5 versus 26.8 per 1000 person-years; P<0.0001) and coronary event rates (37.7 versus 18.0; P=...
Incidence and Clinical Significance of Poststent Optical Coherence Tomography Findings
Authors: Tsunenari Soeda, Shiro Uemura, Seung-Jung Park, Yangsoo Jang, Stephen Lee, Jin-Man Cho, Soo-Joong Kim, Rocco Vergallo, Yoshiyasu Minami, Daniel S. Ong, Lei Gao, Hang Lee, Shaosong Zhang, Bo Yu, Yoshihiko Saito, Ik-Kyung Jang
Journal: Circulation (2015)

Background— Optical coherence tomography (OCT) was recently introduced to optimize percutaneous coronary intervention. However, the exact incidence and significance of poststent OCT findings are unknown. Methods and Results— A total of 900 lesions treated with 1001 stents in 786 patients who had postprocedure OCT imaging were analyzed to evaluate the incidence of poststent OCT findings and to identify the OCT predictors for device-oriented clinical end points, including cardiac death, target vessel–related myocardial infarction, target lesion revascularization, and stent thrombosis. Patients were followed up to 1 year. Stent edge dissection was detected in 28.7% of lesions, and incomplete stent apposition was detected in 39.1% of lesions. The incidences of smooth protrusion, disrupted fibrous tissue protrusion, and irregular protrusion were 92.9%, 61.0%, and 53.8%, respectively. Small minimal stent area, defined as a lesion with minimal stent area &lt;5.0 mm 2 in a drug-eluting stent or &lt;5.6 mm 2 in a bare metal stent, was observed in 40.4% of lesions. One-year device-oriented clinical end points occurred in 33 patients (4.5%). Following adjustment, irregular protrusion and small minimal stent area were independent OCT predictors of 1-year device-oriented clinical end points ( P =0.003 and P =0.012, respectively). Conclusions— Abnormal poststent OCT findings were frequent. Irregular protrusion and small minimal stent area were independent predictors of 1-year device-oriented clinical end points, which were primarily driven by target lesion revascularization.
Norepinephrine Induces the raf-1 Kinase/Mitogen-Activated Protein Kinase Cascade Through Both α1- and β-Adrenoceptors
Authors: TsutomuYamazaki, IsseiKomuro, YunzengZou, SumiyoKudoh, IchiroShiojima, YukioHiroi, TakehikoMizuno, RyuichiAikawa, HiroyukiTakano, YoshioYazaki
Journal: Circulation (1997)

Background Although norepinephrine induces cardiac hypertrophy by activating protein kinase A and C through β- and α1-adrenoceptors, respectively, protein kinase A has been reported to inhibit cell growth in many other cell types. Methods and Results To elucidate the molecular mechanism of norepinephrine-induced hypertrophic responses, we examined the effects of protein kinase A and protein kinase C on the activities of raf-1 kinase and mitogen-activated protein (MAP) kinases and on protein synthesis rates using cultured cardiomyocytes of neonatal rats. Norepinephrine-induced activation of MAP kinases was partially inhibited by either an α1-adrenoceptor blocker (prazosin) or a β-adrenoceptor blocker (propranolol) and was completely abolished by both blockers. Both a β-adrenoceptor agonist, isoproterenol, and an α1-adrenoceptor agonist, phenylephrine, increased the activities of raf-1 kinase and MAP kinases and phenylalanine incorporation into proteins. Furthermore, isoproterenol and phenylephrine synergis...