tbuckley/cabot-search huggingface dataset:
Abstract 1582: Adenosine A3 Receptor Deficiency Exerts Unanticipated Protective Effects on Pressure Overloaded-Induced Left Ventricular Hypertrophy and Dysfunction in Mice
Authors: Zhongbing Lu, John Fassett, Xin Xu, Xinli Hu, Guangshuo Zhu, Jurgen Schnermann, Robert J Bache, Yingjie Chen
Journal: Circulation (2008)

Endogenous adenosine can protect the overloaded heart against the development of hypertrophy and heart failure, but the contribution of A 1 receptors (A 1 R) and A 3 receptors(A 3 R) is not known. To test the hypothesis A 1 R and A 3 R can protect the heart against systolic overload, we exposed A 3 R gene deficient (A 3 R KO) mice and A 1 R KO mice to transverse aortic constriction (TAC). Contrary to our hypothesis, A 3 R KO attenuated 5 weeks TAC-induced left ventricular (LV) hypertrophy (ratio of ventricular mass/body weight increased to 7.6 ±0.3 mg/g in wild type (Wt) mice as compared with 6.3±0.4 mg/g in KO), fibrosis and dysfunction (LV ejection fraction decreased to 43±2.5% and 55±4.2% in Wt and KO mice, respectively). A 3 R KO also attenuated the TAC-induced increases of myocardial ANP and the oxidative stress markers 3-nitrotyrosine(3-NT ) and 4-hydroxynonenal. In addition, A 3 R KO significantly attenuated TAC-induced activation of multiple MAP kinase pathways, and the activation of Akt-GSK signaling pathway. In contrast, A 1 R-KO increased TAC-induced mortality, but did not alter ventricular hypertrophy or dysfunction compared to Wt mice. In mice in which extracellular adenosine production was impaired by CD73 KO, TAC caused greater hypertrophy and dysfunction, and increased myocardial 3-NT, indicates that extracellular adenosine protects heart against TAC-induced ventricular oxidative stress and hypertrophy. In neonatal rat cardiomyocytes induced to hypertrophy with phenylephrine, the adenosine analogue 2-chloroadenosine (CADO) reduced cell area, protein synthesis, ANP and 3-NT. Antagonism of A3R significantly potentiated the anti-hypertrophic effects of CADO. Our data demonstrated that extracellular adenosine exerts protective effects on the overloaded heart, but A 3 R act counter to the protective effect of adenosine. The data suggest that selective attenuation of A 3 R activity might be a novel approach to attenuate pressure overload-induced myocardial oxidative stress, LV hypertrophy and dysfunction. This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota &amp; Wisconsin).
Abstract 6200: Ethnic Differences in Carotid Artery Distensibility: Multi-Ethnic Study of Atherosclerosis
Authors: Dhananjay Vaidya, Sherita H Golden, Susan R Heckbert, Pamela Ouyang
Journal: Circulation (2008)

When African-Americans are compared to Whites, there is a greater incidence of diseases associated with stiffer arteries, including hypertension, stroke and heart failure. There is a paucity of data regarding ethnic differences in arterial stiffness, particularly in persons without known cardiovascular disease. We therefore examined arterial distensibility in the Multi-ethnic Study of Atherosclerosis (MESA). At MESA baseline (2000–2002), 6358 Americans without clinical cardiovascular disease of White (W, 38%), Chinese (C, 12%), African (A, 27%), and Hispanic (H, 22%) ethnicities had carotid diameter measurements by ultrasound and brachial blood pressure measurements during systole and diastole. We estimated carotid distensibility as the slope of the arterial diameter versus pressure in mixed model analysis where each individual’s intercept (carotid diameter at the brachial arterial pressure of 100mmHg) and slope were modeled as random effects. Sex-stratified models were adjusted for age, antihypertensive use, and metabolic variables (see table footnote). The table shows the intercept and distensibility in women and men of different ethnicities. Compared to men, women have smaller diameter and less distensible vessels (both p&lt;0.001). There is ethnic heterogeneity for the diameter intercept (women p&lt;0.001, men p=0.002), and distensibility (both p&lt;0.001). C women have significantly larger carotid diameter than all other ethnicities. W and C men have larger diameter as compared to B and H men. However, W women and W men have greater distensibility than all other ethnicities. In our study, compared with Whites, African-Americans have lower arterial distensibility, which may contribute to greater cardiovascular morbidity and mortality. Lower arterial distensibility in Chinese and Hispanic Americans is a novel finding and would support further study of vascular disease incidence and its prevention in these ethnicities. Table: Carotid Diameter and Distensibility (Mean±SEM from Mixed Model) by Sex and Ethnicity
Book: Autism, Brain and Environment
Authors: Michael Fitzpatrick
Journal: BMJ (2006)

From holding therapy to secretin, from facilitated communication to swimming with dolphins, the world of autism has long attracted promoters of miracle cures, and desperate parents and their children have suffered the consequences. The current vogue in the United States is for a range of “biomedical” investigations and treatments, including exclusion diets, courses of anti-fungals and antibiotics, and chelation therapy. Just like purveyors of earlier, long discredited, cures, advocates of these methods can readily provide moving testimonies for their benefits. But there is no coherent scientific rationale for these treatments and little evidence of their efficacy. There are, however, serious concerns about safety: last summer an autistic boy from the United Kingdom died while receiving chelation therapy in the United States.​States.




Figure 1



Richard Lathe

Jessica Kingsley, £15.99, pp 288ISBN-10: 1 84310 438 5

Rating: ★⋆⋆⋆




Richard Lathe, author of Autism, Brain and Environment, claims that the recent increase in the prevalence of autism (which most authorities attribute to wider diagnosis) is the result of the combined impact of a wide range of environmental toxins on genetically susceptible children. Beginning from tentative suggestions that virtually every metal in the periodic table and numerous chemicals and infectious agents may be involved, he proceeds to the dogmatic assertion that “toxicity, infection and inflammation converge on the limbic brain” resulting in the behavioural features of autism.

Lathe makes a seamless transition from mainstream science to the “grey literature” of the unorthodox biomedical activists. Thus he approves the guidelines on “genetic testing and selective metabolic analysis” set out by the American Academy of Neurology. He does not acknowledge that these support selective metabolic testing only in “the presence of suggestive clinical and physical findings,” which are precisely specified. Nor does Lathe mention the fact that these guidelines explicitly reject a long list of tests that are routinely offered by the alternative authorities recommended in the same paragraph.

While some of Lathe's therapeutic recommendations, such as avoiding “situations of social or psychological stress,” are merely banal, some are more worrying. Thus he indicates that heavy metal chelation “seems obvious,” while acknowledging that its clinical benefit in autism is “not proven beyond all doubt.” It is, of course, entirely unproven, while its dangers are only too well known.

Though Lathe's account has an aura of scientificity (and 1400 references) his central thesis is speculative and his approved treatments are unsupported by scientific evidence. This plausible book risks leading parents—and their children—into the hands of quacks and charlatans.
Abstract 15008: Mechanism and Predictors of Restenosis at the Side Branch Ostium in Coronary Bifurcation Lesions Treated with the 1-Stent Technique: Serial Intravascular Ultrasound Analysis
Authors: Joo-Yong Hahn, Young Bin Song, Jin-Ho Choi, Seung-Hyuk Choi, Sang Hoon Lee, Hyeon-Cheol Gwon
Journal: Circulation (2011)

Background: Restenosis at the SB ostium is one of the major concerns after 1-stent technique. We sought to investigate the mechanisms and predictors of restenosis at the side branch (SB) ostium in ...
A placebo-controlled, double-blind crossover study of fluoxetine in trichotillomania
Authors: G A Christenson, T B Mackenzie, J E Mitchell, A L Callies
Journal: American Journal of Psychiatry (1991)

It has been proposed by some investigators that trichotillomania, a disorder of chronic hair pulling, is a variant of obsessive-compulsive disorder, and some studies have suggested that the antiobessional agents clomipramine and fluoxetine are useful in treating this disorder. The authors investigated the efficacy of fluoxetine in the treatment of trichotillomania.Twenty-one adult chronic hair pullers were recruited into an 18-week placebo-controlled, double-blind crossover study of fluoxetine, in doses up to 80 mg/day. The fluoxetine and placebo treatment phases consisted of 6-week trials of each agent separated by a 5-week washout period. Fifteen subjects (14 female and one male) completed the study; an additional female subject dropped out at 16 weeks after developing a drug reaction.No significant Drug by Period interactions were found in weekly subject ratings of hair pulling, weekly subject ratings of the urge to pull hair, weekly assessments of the number of hair-pulling episodes, or the estimated amount of hair pulled per week.The short-term efficacy of fluoxetine in the treatment of trichotillomania was not demonstrated in this study.
Deletion of 13q14.3 and Not 13q12 Is the Most Common Genetic Abnormality Detected in Chronic Lymphocytic Leukemia Cells
Authors: P. Panayiotidis, K. Ganeshaguru, A.V. Hoffbrand, C. Rowntree, S.A.B. Jabbar, L. Foroni
Journal: Blood (1997)
Abstract 16962: Angiotensin II Limits NO Production by Upregulating Arginase through a Mitogen Activated Protein Kinase-Activating Transcription Factor-2 pathway
Authors: Alia Shatanawi, Alaaldin M Alkilany, Ruth B Caldwell, R. William Caldwell
Journal: Circulation (2011)

Nitric oxide (NO) produced by endothelial nitric oxide synthase (NOS) is needed for normal vascular function. During hypertension, diabetes or aging, elevated levels of arginase (ARG) can compete with NOS for available L-arginine thus reducing vascular NO production. Elevated angiotensin II (Ang II) is a key participant of endothelial dysfunction in many cardiovascular diseases and has been linked to elevated ARG activity. In this study we explored the signaling pathway leading to increased ARG expression/activity in responses to Ang II in bovine aortic endothelial cells (BAEC). Treatment of BAEC with Ang II (10 -7 M, 24 hrs) caused a 40±6% increase (p&lt;0.05) in ARG activity. This was accompanied by 30±8% decrease (p&lt;0.05) in NO production. Our studies indicate involvement of p38 mitogen activated protein kinase (MAPK) in Ang II-induced ARG upregulation and reduced NO production as p38 MAPK inhibitor SB202190 (2 μM) prevented the Ang II-induced increase in ARG activity. Our mouse studies also show involvement of p38 MAPK in Ang II-induced vascular dysfunction associated with elevated ARG activity and ARG expression. Ang II (42 µg/kg/h, sc, 2 wks) caused impaired EC-dependent vasorelaxation in mouse aorta (55±7% vs. 75±8% for control). This impairment was prevented by treatment with p38 inhibitor SB203580 (5µg/kg/day). Ang II also caused a 6.2 fold increase in vascular ARG activity/expression that was completely prevented by p38 MAPK inhibition. Additionally, treatment of BAEC with Ang II causes phosphorylation of activating transcription factor-2 (ATF-2) by 10 minutes with a peak at 30 minutes (3.9 fold). Transfection of BAEC with ATF-2 siRNA prevents Ang II-induced increases in ARG activity/expression and maintains NO production. These results indicate that ATF-2 is necessary for enhanced expression of ARG by Ang II. Collectively our results indicate that Ang II increases endothelial ARG activity/expression through a p38 MAPK-ATF-2 pathway leading to reduced NO production and endothelial dysfunction. Targeting these signaling steps might be therapeutic points for preventing vascular endothelial dysfunction associated with elevated ARG activity/expression.
Abstract 1408: Simvastatin Suppresses Dendritic Cell-induced Autoimmune Myocarditis via Inhibition of Dendritic Cell Activation
Authors: Futamata Nobuyoshi, Hideo Yasukawa, Yusuke Sugi, Hisashi Kai, Daisuke Fukui, Kazuhisa Mawatari, Toyoharu Ohba, Nobuhiro Tahara, Tsutomu Imaizumi
Journal: Circulation (2007)

Background: Immune mediators such as leukocytes and cytokines play a critical role in the pathogenesis of autoimmune myocarditis which is one of causes of dilated cardiomyopathy. Dendritic cells (D...
Abstract 4874: Large-Scale Candidate Gene Association with Human Heart Failure
Authors: Thomas Cappola, Mingyao Li, Jing He, Bonnie Ky, Joan Gilmore, Brendan Keating, Muredach Reilly, Faisel Syed, Scot Matkovich, Gerald Dorn
Journal: Circulation (2008)

Genetic factors that contribute to non-familial heart failure (HF) are largely unknown. Attempts to identify such by whole genome association have implicated genomic loci, but not specific polymorphisms. In contrast, single candidate gene studies have suggested specific variants and mechanisms, but have not all been replicated. Here, we combined the strengths of whole-genome and single candidate gene association studies in the first large-scale candidate gene study of HF in two independent populations. A custom Illumina SNP array containing 45,000 SNPs in ~2,100 genes prioritized by mechanistic relevance in cardiovascular disorders was used to genotype matched Caucasian HF cohorts (ACC/AHA stage C/D; LVEF 31±16%) from two centers, U. of Pennsylvania (708 CHF, 350 controls) and U. of Cincinnati (900 CHF, 300 controls). After careful assessment of genetic ancestry, we compared genotype frequencies in cases vs. controls using logistic regression (PLINK) adjusting for age and gender. To minimize false positives, genes were ranked according to P-value in both study populations and in a combined analysis of all cases vs. all controls. 13 SNPs were associated with all-cause heart failure with P-values ranging from 10 −2 to 10 −5 . These SNPs were located within genes HSPB7, PCSK6, IL1F10, FRMD4B, F2RL1, SLIT2, NOS1AP, MMP12, and IL1RN. Stratified analyses identified 18 SNPs specific for ischemic heart failure (F10, F7, IRS1, NFATC2, IL1R1, SLIT2, CASP8, CORIN, CDKAL1, TRIAD3, CSMD1) and 12 SNPs for non-ischemic heart failure (ACTC1, RYR2, PRKAG2, SCL5A7, ADRA1,TIE1), replicating several previous observations and identifying intriguing new associations. Most of the SNPs were in non-coding regions, and several of these were in genes that show significant changes in expression in failing vs. non-failing human myocardium (NOS1AP, IL1R1, NFATC2). These findings suggest that common variants in cardiovascular genes contribute to the pathogenesis of human heart failure, in part by affecting level of gene expression, and identify specific targets for further mechanistic analyses.
Abstract 13479: Contemporary Predictors of Post-Procedural Bleeding Complications Among Patients Undergoing Percutaneous Coronary Intervention (PCI): Results from the National Cardiovascular Data Registry (NCDR)
Authors: Sunil V Rao, Lisa A Kaltenbach, John Spertus, Ronald J Krone, Mandeep Singh, Eric D Peterson
Journal: Circulation (2011)

Background: Bleeding is a common and potentially modifiable complication of PCI. Bleeding risk prediction models could support tailoring of interventions to minimize bleeding complications and support meaningful risk-adjusted site feedback. Methods: Using detailed clinical data from 583,540 PCI procedures performed from 2/08 to 10/10 at 1066 NCDR participating centers, we updated the NCDR bleeding risk model. The model was then validated in an additional146,648 procedures. Post-PCI bleeding was defined as any of the following occurring within 72 hours after PCI: intracranial hemorrhage, cardiac tamponade, non-bypass surgery-related blood transfusion in patients with a pre-procedure hemoglobin ≥ 8 g/dl, or an absolute decrease in hemoglobin value of ≥ 3g/dl in patients with a pre-procedure hemoglobin ≤ 16 g/dl. Model discrimination and calibration were assessed in the overall population and among varied subgroups. Results: Overall, post-PCI bleeding occurred in 5.74% of cases. The final model included 19 p...
Abstract 8867: High Risk of Cardiac Events in Hypertrophic Cardiomyopathy Patients With Double/Compound Heterozigosity
Authors: Michele Pasotti, Marilena Tagliani, Maurizia Grasso, Alessandra Serio, Fabiana Isabella Gambarin, Andrea Pilotto, Paolo Tarantino, Elena Serafini, Marta Diegoli, Pamela Cassini, Barbara De Giorgio, Eloisa Arbustini
Journal: Circulation (2010)

Background: Hypertrophic Cardiomyopathy (HCM) is myocardial disease caused by mutations of genes coding sarcomeric (sarcomeric HCM) and non sarcomeric proteins (non-sarcomeric HCM). When all known ...
Mapping with a mouse-click
Authors: Tanita Casci
Journal: Nature Reviews Genetics (2001)

Telomerase -the riboprotein enzyme responsible for maintaining chromosome ends -has a complex function in the genesis and progression of cancer: although it is reactivated in many human cancers, its loss in mice sends the incidence of epithelial tumours soaring.In the June issue of Nature Genetics, Ron DePinho and colleagues explain these apparently contradictory observations by dissecting the function of telomerase in tumour initiation from its role in progression.The authors crossed Terc -/-mice, which lack the RNA component of telomerase, with Apc Min mice, which have an inactivating mutation in one copy of the Apc tumour suppressor gene, and develop multiple intestinal neoplasia as a consequence of losing their second Apc allele.Tumour initation and progression were assessed by counting intestinal polyps (microadenomas) and frank tumours (macroadenomas), respectively.Terc -/-mice develop chromosomal instabilities as their telomeres gradually shorten, and chromosome instability becomes manifest in the second generation, increasing further in generations 3 and 4. Surprisingly, although third-and fourth-generation Terc -/- Apc Min mice had more microadenomas than did Terc +/+ Apc Min mice, the number and size of their macroadenomas decreased significantly.This corresponded with a striking increase in survival compared with mice that had longer telomeres.What seems to be happening is that loss of telomerase allows more neoplasias to initiate, but these rarely progress to frank malignancy, even though they clearly have chromosomal instabilities as judged by increased numbers of anaphase bridges.Why, despite this chromosomal instability, do Terc -/-Apc Min mice develop fewer
Impact of Olmesartan on Progression of Coronary Atherosclerosis
Authors: Atsushi Hirohata, Keizo Yamamoto, Toru Miyoshi, Kunihiko Hatanaka, Satoshi Hirohata, Hitoshi Yamawaki, Issei Komatsubara, Masaaki Murakami, Eiki Hirose, Shinji Sato, Keisuke Ohkawa, Makoto Ishizawa, Hirosuke Yamaji, Hiroshi Kawamura, Shozo Kusachi, Takashi Murakami, Kazuyoshi Hina, Tohru Ohe
Journal: Journal of the American College of Cardiology (2010)
Abstract 210: Facilitators to Learning Cardiopulmonary Resuscitation in High-Risk Neighborhoods
Authors: Comilla Sasson, Emily Moreno, Renee King, Susan Colbert, Cindy Bond-Zielinski, Marilyn Rabe, Michael Sayre, Michele Heisler
Journal: Circulation (2011)

Background: Previous research in Columbus, Ohio has identified three high-risk neighborhoods, comprised primarily of African-American residents and with a median household income of &lt;$30,000, where the incidence of OHCA is high and bystander cardiopulmonary (CPR) is low. Objectives: To identify 1) facilitators to learning CPR and 2) perceived attributes of people most likely to learn CPR in high-risk neighborhoods. Methods: Five focus groups, lasting 90-120 minutes, were conducted in January-February 2011 in the three identified neighborhoods in Columbus. We utilized purposeful and snowball sampling to recruit 42 residents to participate. A qualitative study design using grounded theory was used to develop codes, categories and themes in an iterative process. The focus groups were audiotaped and transcribed verbatim. Three reviewers independently read through each transcript and discussed major themes to develop a conceptual framework. Results: Three main thematic areas were identified as facilitators for residents to learn CPR: family/self-preservation, emotional factors and economic incentives (Table 1). The importance of showing how learning CPR might save the lives of family members was the most consistent theme. Participants felt that tying CPR instruction to basic first aid, especially in the setting of traumatic arrest was very important due to the high rates of interpersonal violence in the community. Obtaining academic credit and job skills through CPR training were also important. The participants perceived certain attributes of people likely to learn CPR: self-motivated, concerned and people with prior medical training. Conclusion: Linking CPR instruction to saving the lives of family members and saving the life of a violent crime victim were consistent themes. Future work will be conducted with residents from these neighborhoods to implement and measure the success of a community-based approach to CPR training based on this research.
Abstract 2056: Blockade of PDGF Receptor Tyrosine Kinase by Ex Vivo Nano-DDS of Imatinib Mesylate into the Vein Suppresses Vein Graft Neointima Formation
Authors: Satoshi Kimura, Kensuke Egahira, Hiroyuki Tsujimoto, Kaori Hara, Yoshiaki Kawashima, Ryuji Tominaga, Kenji Sunagawa
Journal: Circulation (2007)

Background: Clinical outcome of surgical revascularization using autologous vein graft is limited by vein graft failure due to neointima formation. Platelet-derived growth factor (PDGF), expressed by vascular smooth muscle cells (VSMCs), plays a central role in the pathogenesis of vein graft failure. Therefore, optimal nanotechnology-based drug delivery system (Nano-DDS) of PDGF receptor tyrosine kinase (TK) inhibitor, imatinib mesylate (STI571), can be an innovative therapeutic strategy for clinical application. We have developed such Nano-DDS using bioabsorbable PLGA nanoparticles (NP) for local ex vivo delivery. Hypothesis: Blockade of PDGF receptor TK by Nano-DDS of imatinib suppresses vein graft neointima formation. Methods and Results: [studies in human VSMCs in vitro] Addition of fluorescence (FITC)-encapsulated NP resulted in rapid and stable uptake by 99 % of cells. The Nano-DDS of imatinib prevented PDGF-induced phosphorylation of PDGF receptor TK, and thus normalized the PDGF-induced proliferation. [ ex vivo studies] Incubation of excised rabbit jugular vein and human saphenous vein ex vivo in FITC-encapsulated NP for 30 min resulted in highly efficient intracellular delivery rate (&gt; 90 % cells) into cells of the venous wall. [ in vivo studies in rabbits] The excised jugular vein was treated ex vivo with PBS, imatinib only (100 mM), FITC NP only, or imatinib NP (100 mM) (n=5– 6, each) for 30 min, and then interposed into the carotid artery position of hypercholesterolemic rabbits. Seven and 28 days after ex vivo FITC NP treatment, FITC-positive cells were detected in many cells in the neointima and media (cellular uptake rate: 60 –70 %). Significant neointima was formed 28 days after grafting in PBS group, which was suppressed in imatinib NP group, but not in FITC NP only or imatinib only groups. Imatinib NP also inhibited the appearance of proliferating PCNA-positive cells and increased phosphorylation of PDGF receptor TK, but did not affect monocyte infiltration or endothelial regeneration process. Conclusions: Nano-DDS of imatinib into the excised vein ex vivo was feasible and suppressed vein graft neointima formation in rabbits. Nano-DDS of imatinib may be a clinically promising therapeutic strategy for prevention of vein graft failure.