tbuckley/cabot-search huggingface dataset:
Abstract 9635: Percutaneous vs. Surgical Pulmonary Valve Implantation: How Does the Right Ventricle Fare?
Authors: Karima Addetia, Giuseppe Martucci, Adrian Dancea, Ariane Marelli, Judith Therrien
Journal: Circulation (2012)

Introduction. Percutaneous pulmonary valve implantation (PPVI) to non-invasively correct pulmonary valve dysfunction is a recent advancement. Cardiopulmonary bypass is known to have a negative impact on right ventricular (RV) function. This study was designed to assess RV recovery using echocardiographic parameters post surgical pulmonary graft placement versus PPVI. Methods. Retrospective study of consecutive adult patients who underwent PPVI and received graft bioprosthesis between 2007 and 2011. Echocardiographic parameters analyzed included tricuspid annular systolic excursion (TAPSE), RV tissue Doppler velocity (TDV), and myocardial performance index (MPI). Graphs of relative differences (between postoperative and preoperative values) for each parameter were constructed to compare preoperative, early (≤60 days) and late postoperative (≥6-12 months) measurements. Significance of results was determined using T-test. Results. Ten patients received PPVI and 26 underwent open heart surgery with graft insertion. Average patient age was 31±20 years. Pre-operative TDV (p=0.008), and MPI (p=0.05) were significantly higher for the surgical population than the percutaneous group. Postoperative, TDV and TAPSE were significantly lower early (p&lt;0.001) and late (p&lt;0.001) in the surgical group than preoperative measures. No significant differences were seen for the PPVI group. On comparison of relative differences in parameters between groups TDI was significantly higher both early (p&lt;0.001) and late (p&lt;0.006) postoperatively in the percutaneous group. Conclusion. RV systolic recovery as measured by TDV and TAPSE was significantly impaired post surgery but relatively unchanged post PPVI. On analysis of relative differences in RV parameters, TDI was significantly higher early and late post PPVI than open-heart surgery suggesting that surgery may impact RV function more significantly than its percutaneous counterpart.
Hemodynamic Sequelae of Cardiac Arrhythmias
Authors: Philipsamet
Journal: Circulation (1973)

The hemodynamic consequences of cardiac arrhythmias depend on various factors, including the ventricular rate and the duration of the abnormal rate, the temporal relationship between atrial and ventricular activity, the sequence of ventricular activation, the functional state of the heart, the irregularity of the cycle length, associated drug therapy, the peripheral vascular vasomotor system, disease in organ systems other than the heart, and the degree of anxiety caused by the disease processes. Sinus bradycardia, even with rates as low as 40 beats/min, may not be associated with significant hemodynamic consequences unless the stroke volume is limited by myocardial or valvular disease, as in acute myocardial infarction. Cardiac output usually, but not invariably, falls when atrial fibrillation replaces normal sinus rhythm, even at comparable ventricular rates, both at rest and during exercise. Similar observations have been made during the development of atrial flutter despite the persistence of effectiv...
Abstract P393: Consumption of Bread and Tortilla and Incidence of Self-Reported Hypertension in Mexican Women
Authors: AdrianaMonge, TonatiuhBarrientos, IsabelleRomieu, RuyLopez-Ridaura, MartinLajous
Journal: Circulation (2014)

Background: Mexico is undergoing a fast-paced epidemiologic and nutritional transition and hypertension affects 31% of Mexicans. Bread and wheat tortilla have almost three times more sodium than corn tortillas and long-term sodium intake may increase the risk of hypertension. Methods and Results: We investigated the relation between bread and tortilla intake and the incidence of self-reported hypertension in 43,619 women from the Mexican Teachers’ Cohort who were free of hypertension at baseline in 2008 when diet was assessed using a food frequency questionnaire. Between baseline and 2011 we identified 2,699 incident cases of self-reported hypertension. Total bread (white and whole grain) and corn and wheat tortilla consumption were categorized into energy-adjusted quintiles and logistic regression models were fit. Median servings per week for extreme categories were 2.0 and 12.5 for total bread (1.4 and 11.0 for white bread; 0.2 and 3.0 for whole grain), 3.0 and 17.5 for corn tortilla, and 0.2 and 3.0 fo...
Abstract 239: Development of DNA chip for detection of predictive SNPs for gemcitabine-induced adverse events
Authors: Noriaki Nakamura, Koichi Hirayama, Hirofumi Yamano, Hiroshi Okamura, Hitoshi Zembutsu
Journal: Cancer Research (2018)

Abstract [Introduction] Anticancer agent gemcitabine is one of the effective chemotherapies and has been widely used for the treatment of patients with various tumors. However, 13-35% of patients receiving gemcitabine experience severe leukopenia/neutropenia. In our previous studies, we identified four novel SNPs (rs11141915, rs1901440, rs11719165 and rs12046844) associated with this toxicity. To predict the risk of gemcitabine-induced myelosuppression, we developed a high accuracy DNA chip system for genotyping of these four SNPs. [Methods] We used 17 and 170 germline DNA samples of patients who received gemcitabine therapy in the first stage and second stage respectively. For SNP genotyping using the DNA chip, we amplified target regions by PCR with 10 ng of DNA extracted from blood samples. The PCR product was hybridized with the probe on the DNA chip. Genotype was detected by genotyping score, which was calculated the ratio of risk allele fluorescence intensity to total fluorescence intensity. To confirm the accuracy and reliability of this method, TaqMan genotyping assay was performed for 187 samples. [Results and Discussion] In the first stage, genotypes of 17 samples were clearly divided into 3 types (non-risk type homo, hetero type, risk type homo). We defined an appropriate cut off value of genotyping score for detection of genotype according to the results of first stage. In the second stage, 170 samples, whose genotype were unknown, were genotyped using the DNA chip. The genotype results were completely concordant (100%) with those using TaqMan genotyping assay. Our DNA chip system is extremely useful as a simple method that is capable of genotyping using DNAs extracted from small amount of blood samples in general hospitals. The development of our DNA chip system provides new insights into personalized anti-cancer drug therapy including gemcitabine for the patients with cancer. Citation Format: Noriaki Nakamura, Koichi Hirayama, Hirofumi Yamano, Hiroshi Okamura, Hitoshi Zembutsu. Development of DNA chip for detection of predictive SNPs for gemcitabine-induced adverse events [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 239.
Gene therapy for C1 esterase inhibitor deficiency in a Murine Model of Hereditary angioedema
Authors: Ting Qiu, Maria J. Chiuchiolo, Adele S. Whaley, Anthony R. Russo, Dolan Sondhi, Stephen M. Kaminsky, Ronald G. Crystal, Odelya E. Pagovich
Journal: Allergy (2018)

Abstract Background Hereditary angioedema ( HAE ) is a life‐threatening, autosomal dominant disorder characterized by unpredictable, episodic swelling of the face, upper airway, oropharynx, extremities, genitalia, and gastrointestinal tract. Almost all cases of HAE are caused by mutations in the SERPING 1 gene resulting in a deficiency in functional plasma C1 esterase inhibitor (C1 EI ), a serine protease inhibitor that normally inhibits proteases in the contact, complement, and fibrinolytic systems. Current treatment of HAE includes long‐term prophylaxis with attenuated androgens or human plasma‐derived C1 EI and management of acute attacks with human plasma‐derived or recombinant C1 EI , bradykinin, and kallikrein inhibitors, each of which requires repeated administration. As an approach to effectively treat HAE with a single treatment, we hypothesized that a one‐time intravenous administration of an adeno‐associated virus ( AAV ) gene transfer vector expressing the genetic sequence of the normal human C1 esterase inhibitor ( AAV rh.10hC1 EI ) would provide sustained circulating C1 EI levels sufficient to prevent angioedema episodes. Methods To study the efficacy of AAV rh.10hC1 EI , we used CRISPR /Cas9 technology to create a heterozygote C1 EI ‐deficient mouse model (S63±) that shares characteristics associated with HAE in humans including decreased plasma C1 EI and C4 levels. Phenotypically, these mice have increased vascular permeability of skin and internal organs. Results Systemic administration of AAV rh.10hC1 EI to the S63± mice resulted in sustained human C1 EI activity levels above the predicted therapeutic levels and correction of the vascular leak in skin and internal organs. Conclusion A single treatment with AAV rh.10hC1 EI has the potential to provide long‐term protection from angioedema attacks in affected individuals.
Abstract 540: β-Catenin/LIN28B promotes cell proliferation of human trophoblast cells via let7a repression
Authors: Jing Wu, Baoxin Luan, Huandi Yu, Yinhua Yu, Congjian Xu, Hongbo Zhao
Journal: Cancer Research (2018)

Abstract LIN28 is a highly conserved RNA-binding proteins, have been implicated in key biological functions such as development, glucose metabolism and pluripotency. LIN28 overexpression induces the reprogramming of pluripotent stem cells (iPSCs) and supports the proliferative and metabolic capacities of iPSCs. Therefore LIN28 is crucial for the regulation of the cell fate and human embryonic development. In addition, LIN28B is frequently up-regulated in a variety of cancers and correlates with poor prognosis and cancer recurrence, indicating the crucial role of LIN28B in tumorigenesis. Aberrantly expression of LIN28B is responsible for the decrease in the let-7 microRNA family observed in many cancers and Let-7 is frequently down-regulated in numerous different tumors and lower levels of let-7 correlates with poor prognosis. Therefore, LIN28/Let7 may be crucial for the regulation of cell cycle and cell proliferation. In our present study, We first detected the expression of LIN28B in normal placental villi and choriocarcinoma tissue. Our data showed LIN28B was highly expressed in human choriocarcinoma tissues and most LIN28B staining was localized in the nucleus. Comparatively, LIN28B staining was faint in normal placental villi. Our data then demonstrated that LIN28B was highly expressed in human choriocarcinoma cell lines JEG-3 and JAR. However, LIN28B expression was undetectable in HTR-8/Svneo normal trophoblast cells. Our data then demonstrated that LIN28B knockdown by small interfering RNA (siRNA) caused an increase in Let-7a expression. Further, silencing of LIN28 inhibited IGF2BP1 expression and suppressed cell proliferation capacity, which can be markedly restored by Le7a siRNA. These findings reveal that LIN28 may promote IGF2BP1 expression and cell proliferation by Let-7a repression. Moreover, β-catenin knockdown resulted in reduced LIN28 expression and Let-7a up-regulation. β-catenin is the major mediator of canonical Wnt signaling pathway, and activation of canonical Wnt signaling has been reported to play a critical role in the proliferation, invasion, and differentiation of various tumors. Collectively, our present data indicated that β-catenin/LIN28B/Let7a pathway may be crucial for cell proliferation regulation in human choriocarcinoma cells. Citation Format: Jing Wu, Baoxin Luan, Huandi Yu, Yinhua Yu, Congjian Xu, Hongbo Zhao. β-Catenin/LIN28B promotes cell proliferation of human trophoblast cells via let7a repression [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 540.
Abstract 18390: Ang II activates the RhoA Exchange Factor Arhgef1 in Humans
Authors: Maria-LuigiaCarbone, JérémyBrégeon, NabilaDevos, AnneBlanchard, MichelAzizi, PierrePacaud, XavierJeunemaitre, GervaiseLoirand
Journal: Circulation (2014)

Introduction: Although a causative role for RhoA-Rho kinase signaling has been recognized in the development of human hypertension, the molecular mechanism(s) as well as the RhoA exchange factors (GEFs) responsible for the over activation of RhoA remain unknown. Arhgef1 has been recently identified as a RhoA GEF involved in Ang II-mediated regulation of vascular tone and hypertension in mice. Hypothesis: Here we assessed the hypothesis that Arhgef1 is activated and involved in the activation of RhoA-Rho kinase signaling by Ang II in humans. Methods: We used in vitro stimulation of human coronary artery smooth muscle cells and human peripheral blood cells (PBMC) by Ang II (0.1 μmol/L), and PBMC isolated from normotensive subjects before and after activation of the renin-angiotensin system by a low-salt diet for 7 days (checked by the increase in plasma aldosterone and active renine). Activation of Arhgef1 was monitored by measuring its tyrosine phosphorylation by western blot and phosphorylation of the Rho...
Biological Gradient Between Long-Term Arsenic Exposure and Carotid Atherosclerosis
Authors: Chih-HaoWang, Jiann-ShingJeng, Ping-KeungYip, Chi-LingChen, Lin-IHsu, Yu-MeiHsueh, Hung-YiChiou, Meei-MannWu, Chien-JenChen
Journal: Circulation (2002)

Background— Long-term exposure to ingested arsenic has been documented to induce peripheral vascular disease, ischemic heart disease, and cerebral infarction in a dose-response relationship. This study further examined the biological gradient between ingested inorganic arsenic and carotid atherosclerosis. Methods and Results— We studied 199 male and 264 female adult residents from the southwestern area of endemic arseniasis in Taiwan. The extent of carotid atherosclerosis was assessed by duplex ultrasonography. Diabetes mellitus was determined by oral glucose tolerance test, hypertension by mercury sphygmomanometers, and serum lipid profiles by autoanalyzers. Information regarding the consumption of high-arsenic artesian well water, cigarette smoking, and alcohol consumption was obtained through standardized questionnaire interviews. Logistic regression analysis was used to estimate the odds ratio and its 95% CI of carotid atherosclerosis for various risk factors. Three indices of long-term exposure to in...
Annular Subvalvular Left Ventricular Aneurysms in the South African Bantu
Authors: Elliotchesler, Normanjoffe, Leoschamroth, Anthonymeyers
Journal: Circulation (1965)

The clinical, radiologic, morbid anatomic, and histologic features of six cases of annular subvalvular left ventricular aneurysms occurring in African subjects are described. The problems of surgical repair are emphasized and the possibilities of antemortem diagnosis discussed.
Abstract 10522: Changes in Prevalence and Risk Factors of Acute Myocardial Infarction in the Rural and Urban District in Japan -Report from MIYAGI-AMI Registry Study
Authors: Kiyotaka Hao, Satoshi Yasuda, Toru Takii, Yoshitaka Ito, Akiko Kawana, Jun Takahashi, Morihiko Takeda, Kenta Ito, Hiroaki Shimokawa
Journal: Circulation (2011)

Background: The MIYAGI-Acute Myocardial Infarction (AMI) Registry Study has prospectively registered all AMI patients in the Miyagi prefecture, which is located in northeastern Japan and includes S...
Peroxisome Proliferator-Activated Receptor γ Plays a Critical Role in Inhibition of Cardiac Hypertrophy In Vitro and In Vivo
Authors: MasayukiAsakawa, HiroyukiTakano, ToshioNagai, HirokiUozumi, HiroshiHasegawa, NaotoKubota, ToshihiroSaito, YoshiakiMasuda, TakashiKadowaki, IsseiKomuro
Journal: Circulation (2002)

Background— Peroxisome proliferator-activated receptors (PPARs) are transcription factors of the nuclear receptor superfamily. It has been reported that the thiazolidinediones, which are antidiabetic agents and high-affinity ligands for PPARγ, regulate growth of vascular cells. In the present study, we examined the role of PPARγ in angiotensin II (Ang II)-induced hypertrophy of neonatal rat cardiac myocytes and in pressure overload-induced cardiac hypertrophy of mice. Methods and Results— Treatment of cultured cardiac myocytes with PPARγ ligands such as troglitazone, pioglitazone, and rosiglitazone inhibited Ang II-induced upregulation of skeletal α-actin and atrial natriuretic peptide genes and an increase in cell surface area. Treatment of mice with a PPARγ ligand, pioglitazone, inhibited pressure overload-induced increases in the heart weight-to-body weight ratio, wall thickness, and myocyte diameter in wild-type mice and an increase in the heart weight-to-body weight ratio in heterozygous PPARγ-defici...
Abstract 3441: Genome-wide gene expression analysis in asbestos-related non-small cell lung cancer
Authors: Eeva Kettunen, Veer Singh Marwah, Henrik Wolff, Dario Greco, Kirsti Husgafvel-Pursiainen
Journal: Cancer Research (2018)

Abstract Recently we examined genome-wide DNA methylation in lung cancer from patients occupationally exposed to asbestos (Kettunen et al 2017 Int J Cancer). Distinct methylation changes in lung tumors were shown in relation to asbestos exposure and tobacco smoking. Now we have performed genome-wide gene expression microarray experiments with Agilent SurePrint G3 Human GE 8x60K v3 Microarrays using same samples. Patients had been interviewed for work and smoking histories and their pulmonary asbestos fiber counts were measured by electron microscopy. Fresh-frozen lung cancer tissues (LC, n=42) and paired microscopically normal peripheral lung tissues (NT, n=21) were studied. After data processing and analyses for differential gene expression, data were filtered for adjusted p &amp;lt; 0.05 and fold change &amp;gt; 1.5. Principal component analysis showed distinct clusters of normal lung and cancer tissues. In lung cancers compared with their paired microscopically normal lung, 5931 genes such as those involved in neutrophil degranulation and immune system were differentially expressed, with the lowest adjusted p=6.71E-37. In our preliminary analyses, 34 genes in NT and 44 in LC, and 152 genes in NT and 12 in LC showed differential expression when the asbestos-exposed were compared to non-exposed and current smokers to ex-smokers, respectively. The genes differentially expressed in relation to smoking or to asbestos exposure had the lowest adjusted p=8.50E-06 and 9.83E-04, respectively. Within differential gene expression related to asbestos exposure, chemokine activity and regulation of cellular protein metabolic processes were implicated whereas microtubules and positive regulation of transcription were related with tobacco smoking burden. In conclusion, comparison of gene expression patterns between lung cancer tissue and paired normal lung showed distinct principal component analysis clusters. Our preliminary data suggest different major biological processes in gene expression for these exposures. Financial support from the Cancer Society of Finland (2014 and 2015) is gratefully acknowledged. Citation Format: Eeva Kettunen, Veer Singh Marwah, Henrik Wolff, Dario Greco, Kirsti Husgafvel-Pursiainen. Genome-wide gene expression analysis in asbestos-related non-small cell lung 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 3441.
Abstract 3823: Bat4306f, an anti-CD20 antibody devoid of fucose modification, demonstrates enhanced ADCC effect and potent in vivo efficacy
Authors: Jin-Chen Yu, Chao Qin, Shengfeng Li
Journal: Cancer Research (2018)

Abstract Depletion of malignant B cells using anti-CD20 antibodies is one of the most effective approaches for CD20-positive non-Hodgkin lymphoma therapy. Anti-CD20 antibodies can activate several pathways including antibody-dependent cellular cytotoxicity (ADCC), complement-dependent cytotoxicity (CDC), or programmed cell death to kill tumor cells. ADCC is mediated via Fc region of antibody binding to FcγRIIIa receptor on effector cells, such as NK cells. Previous studies have shown that non-fucosylated antibody binds to FcγRIIIa with increased affinity and can thus trigger FcγRIIIa-mediated effector functions more efficiently than native, fucosylated antibody. Obinutuzumab, an FDA-approved anti-CD20 antibody with approximate 30% fucose level of a normal antibody, has demonstrated better efficacy than fucosylated rituximab. We generated BAT4306F, which has the same sequence as obinutuzumab yet is completely devoid of fucose modification. BAT4306F induced higher level of ADCC effect compared with rituximab and obinutuzumab in vitro. BAT4306F also showed significantly superior activity on depleting B cells in whole blood compared to rituximab, and superior activity compared to obinutuzumab. In monkeys dosed once with these antibodies, BAT4306F demonstrated much stronger B-cell depletion activity than that of obinutuzumab and rituximab, whether detected in serum, spleen, or lymph node. The residual B cells detected in spleen of monkey treated with BAT4306F were 8-fold less than that of obinutuzumab, and 10-fold less than that of rituximab. Furthermore, BAT4306F demonstrated stronger tumor-inhibition activity than rituximab in a DLBCL tumor cell xenograft mouse model. Preclinical acute and long-term toxicity studies in monkey reveal that BAT4306F is well tolerated. Together these data demonstrate that BAT4306F is more potent than obinutuzumab and rituximab due to a complete defucosylation. The result warrants further clinical development of BAT4306F. Citation Format: Jin-Chen Yu, Chao Qin, Shengfeng Li. Bat4306f, an anti-CD20 antibody devoid of fucose modification, demonstrates enhanced ADCC effect and potent in vivo efficacy [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 3823.