tbuckley/cabot-search huggingface dataset:
CD30 Characterizes Polylobated Lymphocytes and Disease Progression in HTLV-1–Infected Individuals
Authors: Makoto Nakashima, Tadanori Yamochi, Mariko Watanabe, Kaoru Uchimaru, Atae Utsunomiya, Masaaki Higashihara, Toshiki Watanabe, Ryouichi Horie
Journal: Clinical Cancer Research (2018)

Purpose: Although expression of CD30 is reported in a subset of adult T-cell leukemia/lymphoma cases, its clinicopathologic significance is poorly understood. We aimed to characterize CD30-positive cells and clarify their tumorigenic role in human T-cell lymphotropic virus type 1 (HTLV-1)-infected cells.Experimental Design: CD30-positive peripheral blood mononuclear cells from individuals with differing HTLV-1 disease status were characterized, and the role of CD30 signaling was examined using HTLV-1-infected cell lines and primary cells.Results: CD30-positive cells were detected in all samples examined, and the marker was coexpressed with both CD25 and CD4. This cell population expanded in accordance with disease progression. CD30-positive cells showed polylobation, with some possessing "flower cell" features, active cycling, and hyperploidy. CD30 stimulation of HTLV-1-infected cell lines induced these features and abnormal cell division, with polylobation found to be dependent on the activation of PI3K. The results thus link the expression of CD30, which serves as a marker for HTLV-1 disease status, to an active proliferating cell fraction featuring polylobation and chromosomal aberrations. In addition, brentuximab vedotin, an anti-CD30 monoclonal antibody conjugated with auristatin E, was found to reduce the CD30-positive cell fraction.Conclusions: Our results indicate that CD30-positive cells act as a reservoir for tumorigenic transformation and clonal expansion during HTLV-1 infection. The CD30-positive fraction may thus be a potential molecular target for those with differing HTLV-1 disease status. Clin Cancer Res; 24(21); 5445-57. ©2018 AACR.
The Prognosis of Essential Hypertension Treated Conservatively
Authors: Mauricesokolow, Dorotheeperloff
Journal: Circulation (1961)

Four hundred thirty-nine consecutive patients (143 men and 296 women) with essential hypertension were followed on conservative therapy for a minimum of 5 years or until death. The initial blood pressure taken by a standard method and the presence and degree of vascular involvement at the time of registration were recorded on all patients. On the basis of these observations, each patient was classified in one of four classes of over-all hypertensive severity. At the end of the 5-year follow-up period, 161 patients were dead, 78 men and 83 women. The higher mortality among men was significant and was apparent after the first year of follow-up. A progressive rise in 5-year mortality was observed with increasing degrees of initial blood pressure elevation, fundal involvement, cardiac size by radiogram, and electrocardiographic evidence of left ventricular hypertrophy, as well as with progressively higher classification of over-all hypertensive severity. Patients with mild hypertension and minimal cardiovascu...
Abstract 10110: Effects of Inorganic Nitrate on Endothelial Dysfunction Induced by Periodontitis
Authors: DanielFernandes, RayomandKhambata, AmritaAhluwalia
Journal: Circulation (2015)

Introduction: Evidence supports an association between periodontal disease and cardiovascular disease (CVD) risk. Periodontal disease is thought to cause vascular dysfunction contributing to atherogenesis and resulting in an increased risk of stroke and coronary heart disease. Safe therapeutics that might improve vascular function in such patients to reduce risk of CVD is a current unmet need. It is thought that a critical step in the increased CVD risk relates to a periodontitis-induced endothelial dysfunction. Evidence suggests that the intervention of dietary nitrate, to elevate circulating nitrite levels, improves endothelial function. We investigated whether dietary nitrate might provide a method for prevention or reversal of the endothelial dysfunction induced by periodontitis. Methods: Male C57BL6 mice were either untreated or randomly assigned to receive KNO3 or KCl (15 mmol/L; in the drinking water) either 7 days prior or 7 days post ligature placement (periodontitis) or a sham procedure. After 1...
Cartilage Oligomeric Matrix Protein Inhibits Vascular Smooth Muscle Calcification by Interacting With Bone Morphogenetic Protein-2
Authors: YaoyaoDu, YueWang, LiWang, BoLiu, QingyunTian, Chuan-juLiu, TaoZhang, QingboXu, YiZhu, OldbergAke, YongfenQi, ChaochuTang, WeiKong, XianWang
Journal: Circulation Research (2011)

Rationale:Vascular calcification is a significant contributor to cardiovascular morbidity and mortality. We recently reported that cartilage oligomeric matrix protein (COMP) is pivotal for maintaining the homeostasis of vascular smooth muscle cells (VSMCs). Whether COMP affects the process of vascular calcification is unknown. Objective:We aimed to test whether COMP modulates vascular calcification. Methods and Results:VSMC calcification in vitro was induced by calcifying media containing high inorganic phosphate or calcium. In vivo medial vessel calcification was induced in rats by 5/6 nephrectomy with a high-phosphate diet or by periadventitial application of CaCl2 to the abdominal aorta. COMP protein level was markedly reduced in both calcified VSMCs and arteries. COMP deficiency remarkably exacerbated VSMC calcification, whereas ectopic expression of COMP greatly reduced calcification. Furthermore, COMP knockdown facilitated osteogenic markers expression by VSMCs even in the absence of calcifying medi...
Laser treatments in early wound healing improve scar appearance: a randomized split-wound trial with nonablative fractional laser exposures vs. untreated controls
Authors: K.E. Karmisholt, C.A. Banzhaf, M. Glud, K. Yeung, U. Paasch, A. Nast, M. Haedersdal
Journal: British Journal of Dermatology (2018)

In recent years, various lasers have increasingly been applied during wound healing to minimize scar formation. However, no consensus regarding treatment procedures exists. To assess scar formation clinically after three nonablative fractional laser (NAFL) exposures, targeting the inflammation, proliferation and remodelling wound healing phases in patients vs. untreated controls. A randomized controlled trial was performed using a split‐wound design to assess excisional wound halves treated with 1540‐nm NAFL vs. no laser treatment. Three NAFL exposures were provided: immediately before surgery, at suture removal and 6 weeks after surgery. NAFL exposures were applied using two handpieces, sequentially distributing energy deeply and more superficially in the skin (40–50 mJ per microbeam). Evaluated at 3 months of follow‐up, the primary outcome was blinded, on‐site evaluation using the Patient Observer Scar Assessment Scale (POSAS total; range from 6, normal skin to 60, worst imaginable scar). Secondary outcomes comprised blinded evaluation on the Vancouver Scar Scale (VSS) and standardized assessment comparing scar sides, carried out by blinded on‐site, photo and patient assessments. This trial was registered with ClinicalTrials.gov (NCT03253484). Thirty of 32 patients completed the trial. At the 3‐month follow‐up, the NAFL‐treated scar halves showed improvement compared with the untreated control halves on POSAS total: NAFL treated, median 11, interquartile range (IQR) 9–12 vs. control, median 12, IQR 10–16; P = 0·001. The POSAS subitems showed that the NAFL‐treated halves were significantly less red and more pliable, and presented with smoother relief than the untreated controls. VSS total correspondingly revealed enhanced appearance in the NAFL‐treated halves: median 2, IQR 1–2·5 vs. control, median 2, IQR 1·75–3, P = 0·007. The standardized assessment comparing appearance of scar halves demonstrated a low degree of correspondence between on‐site, photo and patient assessments. NAFL‐treated scars were rated as superior to untreated scars by 21 of 29 patients. NAFL‐treated scars showed subtle improvement compared with untreated control scars.
Echocardiography in the Diagnosis of Congenital Mitral Stenosis and in Evaluation of the Results of Mitral Valvotomy
Authors: Nils-Runelundström
Journal: Circulation (1972)

Seven patients with congenital mitral stenosis have been investigated with echocardiography using reflected ultrasound. In all cases the mitral stenosis was combined with other cardiovascular malformations. The results are compared with those obtained at clinical investigation, cardiac catheterization, and operation and/or autopsy. It is concluded that the method is of definite value in diagnosing congenital mitral stenosis, even when this is combined with other cardiovascular malformations. The method is also found to be of value in assessing the severity of mitral stenosis. Three patients have been investigated after mitral valvotomy. It is concluded that the findings at echocardiographic examination agree quite well with the clinical findings and with the results of postoperative cardiac catheterization in the evaluation of the result of mitral valvotomy.
The Legacy Effect in Type 2 Diabetes: Impact of Early Glycemic Control on Future Complications (The Diabetes &amp; Aging Study)
Authors: Neda Laiteerapong, Sandra A. Ham, Yue Gao, Howard H. Moffet, Jennifer Y. Liu, Elbert S. Huang, Andrew J. Karter
Journal: Diabetes Care (2018)

To examine for a legacy effect of early glycemic control on diabetic complications and death.
Abstract 63: A Novel Inotropic Gene Therapy Approach for Aging Induced Cardiac Dysfunction
Authors: Vikram Shettigar, Bo Zhang, Svetlena Tikunova, Brandon Biesiadecki, Paul Janssen, Noah Weisleder, Jonathan P Davis, Mark T Ziolo
Journal: Circulation Research (2017)

We have developed a novel approach to increase cardiac contractility without the deleterious effects of existing inotropes (beta agonists, Ca2+ sensitizers). Using the strengths of protein engineering, we have shown that cardiac function can be directly controlled and strongly influenced by manipulating the Ca2+ dependent switch in cardiac muscle, troponin C (TnC). Our smartly formulated construct, L48Q TnC, is a strong Ca2+ sensitizer. Although effective acutely, long-term inotropic support is detrimental. We transduced mice with AAV9 L48Q TnC at 3 months of age and serially performed echocardiography for 2 years. The current dogma would suggest that chronic Ca2+ sensitization with L48Q TnC should result in a hypertrophic cardiomyopathy and compromised function. Astonishingly, the L48Q TnC mice maintained ejection fraction unlike the progressive decline observed in the controlled, age-matched mice. Furthermore, L48Q TnC mice had an increased rate of survival. Considering cardiovascular disease is an elderly issue, we reasoned L48Q TnC would be beneficial in other age-related cardiovascular problems (i.e., hypertension and pressure-overload). We tested this in two models, transverse aortic constriction (TAC, pressure-overload) and angiotensin II infusion (AngII, hypertension). Consistent with the aging results, L48Q TnC mice displayed enhanced cardiac function (ejection fraction, contractility, relaxation), performance (VO 2max , distance run before exhaustion), less adverse remodeling, and enhanced survival. These studies provide a promising approach (i.e., inotropic support via L48Q TnC) that can be used therapeutically to enhance heart function in a variety of cardiomyopathies associated with aging.
Abstract 1354: TonEBP mediates PCNA polyubiquitination on DNA damage sites via interaction with SHPRH and USP1
Authors: Hyunje Kang, Hyun Park, Eun Jin Yoo, Jun Ho Lee, Soo Youn Choi, Whaseon Lee-Kwon, Kyoo-young Lee, Jin-Hoe Hur, Jeong Kon Seo, Kyungjae Myung, Hyug Moo Kwon
Journal: Cancer Research (2018)

Abstract PCNA ubiquitination is important for DNA damage tolerance in eukaryotic replication. While PCNA monoubiquitination activates a mutagenic translesion synthesis pathway, polyubiquitination activates an error-free template switching for DNA damage bypass. Even though PCNA polyubiquitination is critical for the maintenance of genomic integrity, underlying mechanisms are poorly understood. Here, we report that TonEBP (tonicity-responsive enhancer binding protein) is involved the PCNA polyubiquitination in response to DNA damage. TonEBP sequentially recruited an E3 ubiquitin ligase SHPRH followed by a deubiquitinase USP1 into DNA damaged sites, which showed direct correlation with dynamics of PCNA polyubiquitination. The Rel-homology domain (RHD) of TonEBP, which encircles DNA, was required for the interaction with SHRPH and USP1. Consistent with its importance for DNA damage bypass, knockdown or deletion of RHD in TonEBP increased sensitivity to methyl methanesulfonate. Collectively, TonEBP is a key player in the post-replication DNA repair. Citation Format: Hyunje Kang, Hyun Park, Eun Jin Yoo, Jun Ho Lee, Soo Youn Choi, Whaseon Lee-Kwon, Kyoo-young Lee, Jin-Hoe Hur, Jeong Kon Seo, Kyungjae Myung, Hyug Moo Kwon. TonEBP mediates PCNA polyubiquitination on DNA damage sites via interaction with SHPRH and USP1 [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 1354.
Relative Role of Alkalosis and Sodium Ions in Reversal of Class I Antiarrhythmic Drug–Induced Sodium Channel Blockade by Sodium Bicarbonate
Authors: EliasBou-Abboud, StanleyNattel
Journal: Circulation (1996)

Background Hypertonic sodium salts are used to treat sodium channel–blocking drug cardiotoxicity. The relative roles of alkalinization and increased sodium concentration ([Na+]o) for various drugs are incompletely known. Methods and Results The effects of four class I drugs on action potential characteristics of canine Purkinje fibers at equi-effective concentrations (disopyramide 30 μmol/L, mexiletine 80 μmol/L, flecainide 7 μmol/L, imipramine 5 μmol/L) were studied in the presence of normal Tyrode solution and one altered solution (increased [Na+]o, increased bicarbonate concentration, or both) in each experiment. Combined increases in sodium and bicarbonate concentration significantly reduced the depressant effects of flecainide, imipramine, and mexiletine on phase 0 upstroke (Vmax) but did not alter the effects of disopyramide. The effects of sodium bicarbonate were entirely due to alkalinization in the case of imipramine, but both alkalinization and increased [Na+]o contributed to the interaction wit...
Abstract 4679: Rectal cancer-infiltrating T cells show clonal expansion associated with spatially restricted tolerogenic phenotypes
Authors: Livius Penter, Kerstin Dietze, Felix Aigner, Lars Bullinger, Thomas Blankenstein, Leo Hansmann
Journal: Cancer Research (2018)

Abstract T cell infiltration correlates with prognosis and outcome in colorectal cancer regardless of the tumor stage. However, data on clonal expansion, phenotypes, functions, and spatial distribution of tumor-infiltrating T cells (TILs) are limited. We hypothesized that subsets of clonally expanded rectal cancer-associated T cells are specifically recruited into the tumor and show characteristic phenotypes and functions. Paired TILs and T cells from adjacent unaffected mucosa were isolated from five treatment-naïve rectal cancer patients. Although T cell immune phenotypes were heterogeneous, the frequencies of CD38+, PD-1+, and TIM-3+ cells were significantly higher in CD8+ TILs when compared to T cells from unaffected mucosa (p &amp;lt; 0.05). To track clonal expansion and phenotypes at the single cell level, we combined 13-parameter FACS single cell index sorting with next generation T cell receptor (TCR) and phenotype sequencing. Paired TCRαβ sequences were obtained from 1237 TILs (on average 412 TILs per patient) and 1257 T cells infiltrating the unaffected mucosa (on average 419 T cells per patient) from three selected patients. Clonal T cell expansion was not restricted to TILs and occurred predominantly in CD8+ T cells (p &amp;lt; 0.05). Expanded TIL clones were more frequently TIM-3+, PD-1+, and CD38+ (p &amp;lt; 0.05) and occupied characteristic phenotype compartments when compared to T cells from unaffected mucosa with t-stochastic neighbor embedding (t-SNE) visualization. FOXP3 expression was enriched in non-expanded TILs (p &amp;lt; 0.05). Only 11 out of 179 TIL clones were also detectable in unaffected mucosa of the same patients and these overlapping clones were exclusively PD-1- TIM-3-. In conclusion, rectal cancer is infiltrated by oligoclonal T cells. Selected clones were exclusively detected in TILs suggesting their expansion and recruitment driven by tumor-associated cues. Tolerance was induced i) in an antigen-specific manner by the expression of immune checkpoint molecules predominantly on clonally expanded TILs, and ii) in an antigen-independent manner by infiltrating polyclonal FOXP3+ regulatory T cells. Citation Format: Livius Penter, Kerstin Dietze, Felix Aigner, Lars Bullinger, Thomas Blankenstein, Leo Hansmann. Rectal cancer-infiltrating T cells show clonal expansion associated with spatially restricted tolerogenic phenotypes [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 4679.
Abstract 14593: TemporalTrends of Heart Failure Patients Undergoing Percutaneous Coronary Intervention: Findings From Melbourne Interventional Group Registry
Authors: Ken L Chin, Mark Tacey, Christopher M Reid, Andrew Tonkin, Ingrid Hopper, Angela Brennan, Nick Andrianopoulos, Stephen J Duffy, David Clark, Andrew E Ajani, Danny Liew
Journal: Circulation (2017)

Background: Technological advances have led to an increasing number of patients with left ventricular dysfunction to be referred for revascularisation. However, limited data exist on whether outcomes of heart failure (HF) patients undergoing percutaneous coronary intervention (PCI) have improved over time. The purpose of this study was to assess temporal trends in patient characteristics, treatment and outcomes of HF patients undergoing PCI. Methods: Using data from the Melbourne Interventional Group (MIG), we evaluated temporal trends of the procedure volume, major adverse cardiac events (MACE; a composite of all-cause mortality, myocardial infarction and target vessel revascularisation) and rates of cardiovascular readmission, all-cause death and cardiovascular death in consecutive HF patients undergoing PCI. Change over time was assessed by Box-Jenkins autoregressive integrated moving average (ARIMA) models. Goodness-of-fit was assessed using minimal Akaike and Bayesian Information Criterion. The predi...
Coronary Arterial Flow-Velocity Dynamics in Children With Angiographically Normal Coronary Arteries
Authors: KenjiHamaoka, ZenshiroOnouchi, YutakaOhmochi, KohichiSakata
Journal: Circulation (1995)

Background There have been few reports about coronary hemodynamics in children during the process of growth. In the present study, to assess the characteristics of coronary flow dynamics in children, we examined the phasic coronary flow-velocity (CFV) patterns at rest and during peak hyperemic responses in children with angiographically normal coronary arteries. Methods and Results Spectral Doppler phasic coronary flow velocity was recorded with a 0.018-in intracoronary Doppler guidewire at rest and during peak responses after intracoronary bolus injection of ATP in 30 patients with Kawasaki’s disease (age, 8.2±5.1 years; 24 boys and 6 girls) without angiographic coronary lesions. Average peak velocity (APV), maximum peak velocity (MPV), and diastolic-to-systolic velocity ratio (DSVR) were evaluated in the left anterior descending coronary artery (LAD), left circumflex artery (LCx), and right coronary artery (RCA). Coronary vasodilator reserve (coronary flow reserve [CFR]) was calculated as the ratio of A...
Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer
Authors: Karen E. Hoffman, K. Ranh Voong, Lawrence B. Levy, Pamela K. Allen, Seungtaek Choi, Pamela J. Schlembach, Andrew K. Lee, Sean E. McGuire, Quynh Nguyen, Thomas J. Pugh, Steven J. Frank, Rajat J. Kudchadker, Weiliang Du, Deborah A. Kuban
Journal: Journal of Clinical Oncology (2018)

Hypofractionated radiotherapy delivers larger daily doses of radiation and may increase the biologically effective dose delivered to the prostate. We conducted a randomized trial testing the hypothesis that dose-escalated, moderately hypofractionated intensity-modulated radiation therapy (HIMRT) improves prostate cancer control compared with conventionally fractionated IMRT (CIMRT) for men with localized prostate cancer.
Abstract 5688: Humanized double knock-in mouse models for evaluating in vivo efficacy of the combination therapy of immune-oncology drugs
Authors: Tian Gan, James Jin, Chaoshe Guo, Yuelei Shen, Yanan Guo
Journal: Cancer Research (2018)

Abstract Over the past years, monoclonal antibodies have been successfully utilized in clinical trials to block or activate key mediators of immune checkpoint pathways, including CTLA-4, PD-1, PD-L1 and OX40 et.al,. Although significant benefits including complete regression and long-term survival were reported among the majority of participants, not all patients respond. In order to optimize the efficacy and minimize toxicities of anticancer immunotherapies, immune checkpoint antibodies are being tested in combination with other conventional therapeutics (radiation, chemotherapy and targeted therapies) and newer immunotherapies (cancer vaccines, oncolytic viruses). However, along the IO drug development process, in vivo efficacy models have always been a rate-limiting step, especially for the combination therapy of two IO antibodies. Therefore, we generated humanized double knock-in mouse to evaluate the in vivo efficacy of combination therapy. For example, humanized double Knock-in B-hPD-1/hOX40 mice pairing with mouse cancer cells, demonstrated a synergistic effect of using hPD-1 and hOX40 antibodies. Additionally, more double knock-in mice targeting immune checkpoint molecules were developed, such as B-hPD-1/hPD-L1, B-hPD-1/hCTLA-4, B-hPD-1/hLAG3, B-hPD-1/hTIM3, B-hPD-1/hTIGIT, B-hPD-1/hBTLA, et al,. Humanized double knock-in mice, represent useful in vivo efficacy models for evaluation of the combination effects of various IO drugs. Citation Format: Tian Gan, James Jin, Chaoshe Guo, Yuelei Shen, Yanan Guo. Humanized double knock-in mouse models for evaluating in vivo efficacy of the combination therapy of immune-oncology drugs [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 5688.
Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis
Authors: ManikandanSubramanian, EdwardThorp, IraTabas
Journal: Circulation Research (2015)

Rationale:Granulocyte macrophage colony-stimulating factor (GM-CSF, Csf2) is a growth factor for myeloid-lineage cells that has been implicated in the pathogenesis of atherosclerosis and other chronic inflammatory diseases. However, the role of GM-CSF in advanced atherosclerotic plaque progression, the process that gives rise to clinically dangerous plaques, is unknown. Objective:To understand the role of GM-CSF in advanced atherosclerotic plaque progression. Methods and Results:Ldlr−/− mice and Csf2−/−Ldlr−/− mice were fed a Western-type diet for 12 weeks, and then parameters of advanced plaque progression in the aortic root were quantified. Lesions from the GM-CSF–deficient mice showed a substantial decrease in 2 key hallmarks of advanced atherosclerosis, lesional macrophage apoptosis and plaque necrosis, which indicates that GM-CSF promotes plaque progression. Based on a combination of in vitro and in vivo studies, we show that the mechanism involves GM-CSF–mediated production of interleukin-23, which ...