tbuckley/cabot-search huggingface dataset:
FRI0605 The use of hand perfusion scintigraphy to assess raynaud's phenomenon associated with hand-arm vibration syndrome
Authors: KA Lee, HW Chung, S-H Lee, H-R Kim
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Raynaud9s phenomenon (RP) is a prominent manifestation of hand-arm vibration syndrome (HAVS). Previous studies have evaluated the diagnostic validity and characteristics of hand perfusion scintigraphy. However, no study to date has classified or differentiated the findings of this technique based on the aetiology of RP. <h3>Objectives</h3> This study aimed to evaluate the hand perfusion scintigraphic features of hand-arm vibration syndrome (HAVS) and to compare these with the features of primary and secondary Raynaud9s phenomenon (RP) associated with connective tissue disease (CTD). <h3>Methods</h3> Hand perfusion scintigraphy was performed in 57 patients with primary RP, 71 patients with HAVS-related RP, and 36 patients with CTD-related RP. We calculated 6 ratios by using the time-activity curve and static blood pool images, the chilled to ambient hand and wrist ratios of the first peak height, initial slope, and blood pool uptake. We analysed 3 morphologic characteristics: slow progress pattern, paradoxically increased uptake pattern in the time-activity curve, and the inhomogeneous radioactivity uptake in the blood pool image. <h3>Results</h3> All of the 71 patients with HAVS-related RP were mine workers. The onset of RP after exposure to vibration was at 21.8±7.3 years, with 26.3±7.0 years of vibration exposure time. The chilled to ambient hand ratios of the first peak height and the initial slope were significantly lower in patients with HAVS-related occupational RP than in patients with primary RP. The presence of a paradoxically increased uptake pattern was significantly lower in HAVS than in primary RP. <h3>Conclusions</h3> There were significant differences in hand perfusion scintigraphic features between primary RP and HAVS. These results suggest that the underlying pathophysiology of the two diseases differs; thus, different criteria might be applied for their evaluation <h3>References</h3> Palmer KT, Bovenzi M. Rheumatic effects of vibration at work. Best Pract Res Clin Rheumatol 2015;29:424–39. <h3>Acknowledgements</h3> The author(s) received no financial support for the research, authorship, and/or publication of this article. <h3>Disclosure of Interest</h3> None declared
Abstract 3702: A novel nanoparticle-based theranostic agent targeting low-density lipoprotein receptor-related protein-1 enhances the efficacy of neoadjuvant radiotherapy in colorectal cancer
Authors: Kyoung Jin Lee, Serk In Park, Seong-Yun Jeong, Eun Kyung Choi
Journal: Cancer Research (2018)

Abstract Neoadjuvant radiotherapy is becoming an important therapeutic option for colorectal cancer (CRC) patients, although complete tumor response is observed only in 20 to 30% patients. However, precise biologic mechanisms underlying resistance to radiotherapy remain to be elucidated. In this study, we established a radiotherapy-resistant CRC patient-derived xenograft (PDX) mouse model, and we discovered that low-density lipoprotein receptor-related protein-1 (LRP-1) is increased in radiotherapy-resistant tumors compared with radiotherapy-sensitive tumors. Immunohistochemistry, mRNA and protein expression analyses of radiotherapy-sensitive vs. -refractory CRC patient samples confirmed a statistically significant association between LRP-1 levels and radiotherapy resistance of CRC. We also found that LRP-1 expression is significantly associated with the prognosis of CRC patients by analyzing gene expression data of CRC patients in Gene Expression Omnibus public database. Subsequently, aiming to develop radio-sensitizing nanoparticles targeting LRP-1 for chemotherapeutic drug delivery and in vivo imaging, we screened and identified an LRP-1-binding peptide in a radiotherapy-resistant CRC PDX mouse model using M13 phage display. We next engineered human serum albumin nanoparticles (HSA NPs) containing the LRP-1-binding peptide (for tumor localization), 5-FU (for cytotoxic chemotherapy) and Cy7 fluorophore (for in vivo imaging). When administered in CRC PDX-bearing mice, the LRP-1-targeting HSA NPs accumulated specifically in the CRC tumor tissue and dramatically increased the efficacy of radiotherapy. In addition, whole-body fluorescence imaging of PDX CRC-bearing mice showed that the HSA-NP accumulated only in radiation-treated tumors with high ROI values. In summary, we identified that LRP-1 is a novel signature protein of radiotherapy-resistant CRC, and validated that LRP-1 is closely associated with the progression of CRC. We developed a novel HSA nanoparticle-based theranostic agent loaded with LRP-1-binding peptide, 5-FU and a fluorophore that is applicable to both diagnostic imaging and radio-sensitizing neoadjuvant therapy of CRC. This approach is clinically applicable to improve the effectiveness of neoadjuvant radiotherapy and increase the ratio of complete tumor response in radio-resistant CRC. Citation Format: Kyoung Jin Lee, Serk In Park, Seong-Yun Jeong, Eun Kyung Choi. A novel nanoparticle-based theranostic agent targeting low-density lipoprotein receptor-related protein-1 enhances the efficacy of neoadjuvant radiotherapy in colorectal cancer [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 3702.
Inhibition of Nitric Oxide Synthesis Increases Adenosine Production via an Extracellular Pathway Through Activation of Protein Kinase C
Authors: TetsuoMinamino, MasafumiKitakaze, KoichiNode, HiroharuFunaya, MasatsuguHori
Journal: Circulation (1997)

Background NO is known to deactivate protein kinase C (PKC). Because we have reported that the activation of PKC activates ecto-5′-nucleotidase, we examined whether the inhibition of NO synthesis increases ecto-5′-nucleotidase activity through the activation of PKC. Methods and Results The left anterior descending coronary artery (LAD) was cannulated and perfused with blood through a bypass tube from the left carotid artery in 65 open-chest dogs. The intracoronary administration of NG-nitro-l-arginine methyl ester (L-NAME, 10 μg · kg−1 · min−1), an NO synthase inhibitor, for 30 minutes increased (P<.05) adenosine levels in coronary venous blood (123±10 versus 21±3 pmol/mL) and ecto-5′-nucleotidase activity (64±6 versus 41±4 nmol · mg−1 · min−1) in the LAD-perfused myocardium. The intracoronary administration of α,β-methyleneadenosine 5′-diphosphate, an inhibitor of ecto-5′-nucleotidase, or GF109203X or calphostin C, both of which are PKC inhibitors, attenuated the L-NAME–induced increases in adenosine lev...
Short-Term Oral Endothelin-Receptor Antagonist Therapy in Conventionally Treated Patients With Symptomatic Severe Chronic Heart Failure
Authors: GaborSütsch, WolfgangKiowski, Xiao-WeiYan, PatrickHunziker, StefanChristen, WernerStrobel, Jong-HunKim, PeterRickenbacher, OsmundBertel
Journal: Circulation (1998)

Background—The vasoconstrictor peptide endothelin-1 (ET-1) is important for increased vascular tone in patients with chronic heart failure, but the effects of endothelin-receptor blockade in addition to conventional triple therapy are unknown. Methods and Results—Thirty-six men (mean age±SD, 55±8 years) with symptomatic heart failure (NYHA class III; left ventricular ejection fraction, 22.4±4.5%) despite treatment with diuretics, digoxin, and ACE inhibitors received, in a double-blind and randomized fashion, either additional oral bosentan (1.0 g BID; n=24) or placebo (n=12) over 2 weeks. Hemodynamic and hormonal (plasma ET-1, norepinephrine, renin activity, and angiotensin II) measurements were obtained before and repeatedly for 24 hours after administration of bosentan on days 1 and 14. Bosentan was discontinued in 1 patient with symptomatic hypotension, and 2 patients (bosentan group) declined hemodynamic investigations on day 14. Compared with placebo, bosentan on day 1 significantly decreased mean ar...
Noninvasive Quantification of Left-to-Right Shunt in Pediatric Patients
Authors: PhilippBeerbaum, HermannKörperich, PeterBarth, HermannEsdorn, JürgenGieseke, HansMeyer
Journal: Circulation (2001)

Background—Blood flow can be quantified noninvasively by phase-contrast cine MRI (PC-MRI) in adults. Little is known about the feasibility of the method in children with congenital heart disease. Methods and Results—In 50 children (mean age 6.2 years, range 1.1 to 17.7 years) with an atrial- or ventricular-level shunt, blood flow rate in the great vessels was determined by PC-MRI, and the ratio of pulmonary to aortic flow (Qp/Qs) was compared with Qp/Qs by oximetry. We found a difference of 2% and a range of −20% to +26% (limits of agreement, mean±2 SD). In another 7 children with congenital heart disease but no cardiac shunting (mean age 7.9 years, range 1.3 to 13.5 years), Qp/Qs by PC-MRI was 1.02 (SD ±0.06). No difference between systemic venous and aortic flow volumes was found (range −17% to +20%, n=37). Blood flow through a secundum atrial septal defect as assessed by PC-MRI (n=24) overestimated the shunt compared with the difference between pulmonary and aortic flows. The mean difference betw...
Abstract 17167: Identification of Circulating Stem Cells Originating From the Endocardium of the Human Heart
Authors: Han-Mo Yang, Ju-Young Kim, Hyun-Jai Cho, Joo-Eun Lee, Sooryeonhwa Jin, So-Jung Lim, Sahmin Lee, Hae-Young Lee, Byung-Hee Oh, Young-Bae Park, Hyo-Soo Kim
Journal: Circulation (2013)

Background: There have been several studies showing the presence of cardiac stem cells in myocardium and epicardial progenitor cells in epicardium, respectively. Until recently, however, there has been no report showing the presence of stem cells in the endocardium. In this study, we identified circulating multipotent stem cells from human peripheral blood. Furthermore, we investigated the origin of these cells and the differentiation potential in vivo. Methods and Results: From human peripheral blood mononuclear cells grown on non-coated dishes, we identified a new population of cells, which were quite distinct from previously reported other stem cells. Newly identified cells had the gene profiles such as Oct3/4, KLF4, Nanog, and c-Myc. Moreover, FACS analysis excluded the possibility that these cells might be hematopoietic stem cells. To investigate the origin of these cells, we collected peripheral blood from patients receiving the transplantation of bone marrow, liver, heart, or kidney. After culturin...
Abstract 14346: Correlation of Corevalve Device Implantation ‘Cover Index’ With One Month Aortic Regurgitation
Authors: Manolis Vavuranakis, Konstantinos Kalogeras, Angelos_Michail Kolokathis, Maria Lavda, Dimitrios Vrachatis, Maria Kariori, Evelina Bei, Sophia Vaina, Gerasimos Siasos, Euaggelos Oikonomou, Dimitrios Tousoulis
Journal: Circulation (2015)

Introduction: Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) has been demonstrated to be related with haemodynamic deterioration and left ventricle remodeling, leading to impaired long-term prognosis. ‘Cover index’ has been proposed to appraise the congruence between the aortic annulus and the device, correlating with AR after device deployment. Hypothesis: Hypothesis of the study was that the annulus-prosthesis-size mismatch, as expressed through ‘cover index’, is correlated with one month AR after implantation of a self-expandable aortic prosthesis. Methods: From June 2008 until June 2014, patients who had undergone TAVI with the CoreValve device, were retrospectively studied. The ‘cover index’ was evaluated, as previously shown, as a ratio of: 100 X ([prosthesis diameter - annulus diameter]/prosthesis diameter). The aortic valve regurgitation was echocardiographically evaluated early after the device employment and at 30 days after TAVI and classified as none, mild and moderate. Results: A total of 133 patients (mean age 80.5±5.4 yrs, 72 males) were finally enrolled. The implantation was performed either transfemoraly, or through subclavian route (15 patients). Immediately after the implantation, no statistically significant difference was detected, regarding the evaluated ‘cover index’, between the assessed AR classifications. However, a statistically significant difference was found for the ‘cover index’ between the three one month post-TAVI aortic regurgitation classifications (18.7±4.2 for none AR, 17.2±5mm for mild and 15.2±3.9mm for moderate AR, p=0.037 between groups), indicating increased AR for lower ‘cover index’. Conclusions: The congruence between the aortic annulus and the device, as expressed with ‘cover index’, is strongly correlated with the mid-term one month AR after CoreValve implantation. These data reinforce the importance of appropriate pre-procedural aortic valve sizing and the dynamic component of the self-expandable valves during the early post implantation period.
Abstract 590: Marital status and survival among breast cancer patients
Authors: Yan Lu, Bradford E. Jackson, Bassam Ghabach, Rohit P. Ojha
Journal: Cancer Research (2018)

Abstract Background: Recent evidence suggests improved survival for married breast cancer patients compared with unmarried patients, but unclear is whether this survival benefit extends to socioeconomically disadvantaged women. We aimed to assess the association between marital status and breast cancer survival among socioeconomically disadvantaged breast cancer patients and breast cancer patients from the general population. Methods: We used data from the John Peter Smith (JPS) Oncology Registry, which comprises cancer patients in Tarrant County, TX treated at a safety-net institution, and the Texas Cancer Registry (TCR), a statewide population-based registry. Our eligible population included females aged 18 – 64 years diagnosed with primary breast cancer between January 2008 and June 2013 with follow-up through 2016. We categorized marital status into three groups: single, married, or separated/divorced/widowed. We estimated the 36-month restricted mean survival time, which allows survival comparisons within a specified period. Results: Our study populations comprised 614 JPS and 32,985 TCR patients. The age distribution at diagnosis was similar for both groups (JPS: median=51 years; TCR: median=52 years). JPS patients were more often non-White (JPS=62%; TCR=42%) and uninsured (JPS=56%; TCR=9.6%). A higher frequency of TCR patients were married (TCR=65%; JPS=39%). Survival was shorter for JPS patients (JPS=33.1 months; TCR =34.8 months) after 36-months (Table 1). Married women had longer survival than unmarried women in both populations. Conclusion: Our results suggest similar magnitudes of improved survival for married women with breast cancer compared with unmarried women in both populations, but socioeconomically disadvantaged patients have consistently lower survival estimates across marital subgroups compared with patients from the general population. Our findings warrant further studies that explore mechanisms of how marital status influences breast cancer survival in different populations. Table 1. Restricted mean survival time (RMST) after breast cancer diagnosis based on marital statusDisadvantaged Cancer PatientsaCancer Patients from General PopulationbRMSTc (months)Difference in RMST (95% CLd) (months)RMST (months)Difference in RMST (95% CL) (months)Separated/Divorced/Widowed32.2-0.89 (-2.8, 1.0)34.10.01 (-0.23, 0.25)Married33.80.56 (-0.96, 2.1)35.10.54 (0.36, 0.71)Single33.00 (Reference)34.10 (Reference)aCancer patients from JPS Oncology RegistrybCancer patients in the Texas Cancer RegistrycBased on 36-month restricted mean survivaldCL: Confidence limits Citation Format: Yan Lu, Bradford E. Jackson, Bassam Ghabach, Rohit P. Ojha. Marital status and survival among breast cancer patients [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 590.
Immune mechanism of action of talabostat: a dipeptidyl peptidase targeted antitumor agent
Authors: Michael Jesson, Paul McLean, Glenn Miller, Sharlene Adams, Justin Aubin, Barry Jones
Journal: Cancer Research (2007)

1894  Talabostat (PT-100, L-valinyl-L-boroproline) is a selective inhibitor of the dipeptidyl peptidase (DPP) IV/CD26 family of serine proteases and exhibits potent antitumor activity in mice. In tumor stroma, talabostat can directly target FAP expressed by reactive fibroblasts. Talabostat also stimulates innate and adaptive immune responses against tumors involving transcriptional upregulation of cytokines and chemokines. In vivo and in vitro studies have elucidated the immunostimulatory mechanism of action. The role of IL-1 in vivo was indicated by the abrogation of both cytokine/chemokine responses and antitumor activity in B6.129S7-Il1r1tm1Imx mice deficient in the type I IL-1 receptor (IL-1RI) and B6 mice treated with IL-1 receptor antagonist. In vitro, talabostat upregulated cytokines/chemokines in human bone marrow stromal cells, and flow cytometry suggested an interaction between stromal fibroblasts and monocytes was involved. Similar cytokine/chemokine responses were obtained in talabostat stimulated cocultures of PMA-differentiated THP-1 monocytic cells and the MM46T fibroblast cell line. Sensitivity to inhibition by anti-IL-1β or anti-IL-1RI antibody indicated that cytokine/chemokine upregulation resulted from IL-1β autocrine stimulation of THP1 cells and paracrine stimulation of MM46T cells. Talabostat induced IL-1β in PMA-differentiated THP-1 cells incubated in MM46T cell-conditioned medium, thereby allowing analysis of molecular targets in a monoclonal system. Highly selective inhibitors of DPP 8 and DPP 9--cyclohexylglycine (PTX-1200) and 1-(4,4’-difluor-benzhydryl)-piperazine in amide linkage to aspartate β-carboxyl (PTX-1210) derivatives of isoindoline--induced IL-1β in THP-1 cells similarly to talabostat. DPP 8 and 9 are closely related members of the DPP-IV/CD26 family. Incubation of THP-1 cells with talabostat, PTX-1200 or PTX-1210 caused activation of caspase-1 in a fluorogenic assay with the synthetic substrate N-acetyl-Trp-Glu-His-Asp-trifluoromethylcoumarin. Caspase-1 activation and secretion of mature IL-1β were detectable after 2 hours and, thereafter, both increased with similar kinetics up to 4 hours. Caspase-1 activation is a critical regulatory checkpoint for processing of pro-IL-1β into mature, secreted IL-1β. DPP 8 and 9 are expressed in the cytoplasm where caspase-1 activation occurs. Their involvement in the process suggests that DPP activity could regulate the cytosolic levels of polypeptides involved in signaling the assembly of the inflammasome complex required for the processing of the caspase-1 zymogen. Although DPP 8 and 9 are widely distributed in normal tissues, the induction of IL-1β by talabostat will primarily occur in cells of the monocyte/macrophage lineage that co-express pro-caspase-1 and pro-IL-1β.  *M. Jesson, P. McLean, and G. Miller contributed equally to this work.
Differences in Short-Term Versus Long-Term Outcomes of Older Black Versus White Patients With Myocardial Infarction
Authors: Robin Mathews, Anita Y. Chen, Laine Thomas, Tracy Y. Wang, Chee Tang Chin, Kevin L. Thomas, Matthew T. Roe, Eric D. Peterson
Journal: Circulation (2014)

Blacks are less likely than whites to receive coronary revascularization and evidence-based therapies after acute myocardial infarction, yet the impact of these differences on long-term outcomes is unknown.
Endocrine Deficiency As a Function of Radiation Dose to the Hypothalamus and Pituitary in Pediatric and Young Adult Patients With Brain Tumors
Authors: Ralph E. Vatner, Andrzej Niemierko, Madhusmita Misra, Elizabeth A. Weyman, Claire P. Goebel, David H. Ebb, Robin M. Jones, Mary S. Huang, Anita Mahajan, David R. Grosshans, Arnold C. Paulino, Takara Stanley, Shannon M. MacDonald, Nancy J. Tarbell, Torunn I. Yock
Journal: Journal of Clinical Oncology (2018)

Purpose There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. Materials and Methods Dosimetric and clinical data were collected from children and young adults (&lt; 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. Results Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. Conclusion Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.
Evaluation of Myocardial Metabolism in Ischemic Heart Disease
Authors: Richardgorlin
Journal: Circulation (1969)

Metabolism of the human heart during myocardial infarction may be studied by means of arterial and coronary sinus catheterization at little risk, but definite inconvenience. Ischemia has been readily detected through myocardial production or release of lactate, potassium, hydrogen, and certain enzymes. These findings may be of help in identifying the presence of acute myocardial injury or infarction and in evaluation of applied therapy. Other studies, particularly of metabolized substrates, including oxygen, have been less rewarding. The patchy nature of coronary atherosclerosis and its partial compensation by collateral vessels renders coronary venous inflow nonuniform. This makes interpretation of the meaning of the concentration of substances contained within the coronary venous effluent extremely difficult. Multiple-site venous sampling is particularly helpful in overcoming this inherent defect in the method.