tbuckley/cabot-search huggingface dataset:
Human Chromosomes: I. Preparation, Analysis, and Diagnostic Implications of Abnormalities
Authors: K L Moore, J C Hay
Journal: JAMA (1963)

This presentation is designed to show the diagnostic implications of chromosomal abnormalities, and how in some cases chromosome analysis may be helpful in prognosis and counselling. Most males with Klinefelter's syndrome have chromatinpositive nuclei and an abnormal sex chromosome complex (usually XXY). In Turner's syndrome many such females have chromatin-negative nuclei and a deficient sex chromosome complex (usually XO). Multiple-X females have unusual chromatin patterns (two or three masses of sex chromatin) and abnormal sex chromosome complexes (XXX, XXXX, XO/XXX, etc.). One of the parents of a translocation mongol may carry a translocation chromosome and pass it to future children. Cytogenetic data are therefore essential for genetic counselling. Mosaic and deletion mongols may show incomplete manifestations of mongolism, which make diagnosis difficult; chromosome analysis is helpful in diagnosis, and in prognosis concerning mental development. Abnormal chromosome numbers result from non-disjunction, usually during gametogenesis. The error may occur, however, during cleavage, producing cells with different chromosome complements (mosaicism). Visible structural abnormalities of chromosomes result from deletions or translocations of chromosome fragments.
Abstract 4938: Agtrl-1/Apelin Binding Specifically Enhances Myocardial Ischemia Driven Neovascularization and Left Ventricular Function by Attracting EPCs
Authors: Dennie Tempel, Robert J Herpers, Elza D van Deel, Martine de Boer, Frank Bos, Esther H van de Kamp, Remco A Haasdijk, Stefan Schulte-Merker, Henricus J Duckers
Journal: Circulation (2009)

The molecular mechanisms that govern the formation of new blood vessels following ischemia remain largely unknown. In order to identify new genes involved in blood vessel formation, we performed a genome-wide microarray screen using the affymetrix platform in mice and zebrafish. Gene expression profiles of isolated Flk1+ angioblasts during murine and piscine embryonic development were compared to those of Flk1− cells. Angiotensin receptor 2 like 1 (Agtrl-1) is one of the genes that was identified. In adult C57bl/6 mice Agtrl-1 is highly expressed in mature endothelial cells and was also detected in cKit+/Flk1+/Lin- cells, but not in Sca+/Flk1+/Lin- cells. Remarkably, the number of cKit+/Flk1+/Agtrl-1 cells was increased in the ischemic area after myocardial ischemia (P&lt;0.001), but not after hind limb ischemia. Apelin protein expression, the endogenous ligand of Agtrl-1, was also augmented by 3-fold in the infarct region of the myocardium (P&lt;0.01) and systemic infusion of Apelin increased the recruitment cKit+/Flk1+ EPCs to the circulation by two-fold (P&lt;0.03). Injection of Apelin into the ischemic myocardium resulted in increased homing to the injection site of this specific population and a two-fold increase in neovascularization of the ischemic tissue (P&lt;0.01), consequently improving cardiac function, left ventricular dimensions and diminished scar formation. These findings indicate for the first time, that apelin in response to myocardial ischemia could function as a specific chemoattractant for Agtrl-1+ EPCs, stimulating migration into the infarcted area and subsequently promoting neovascularisation and myocardial repair.
Factors Related to Long-term Traumatic Stress Responses in Survivors of Torture in Turkey
Authors: Metin Başoğlu
Journal: JAMA (1994)

<h3>Objective.</h3> —To examine factors related to long-term psychological functioning in political ex-prisoners who had been subjected to systematic torture. <h3>Design.</h3> —The psychological status of 55 tortured political activists, 55 nontortured political activists, and 55 subjects with no history of torture or political activism was assessed using Structured Clinical Interview for DSM-III for psychiatric assessment, Semi-structured Interview for Survivors of Torture, and other self-rated and assessor-rated measures of anxiety, depression, and posttraumatic stress disorder (PTSD). Correlational and multiple regression analyses were used to assess the independent effects of precaptivity, captivity, and postcaptivity variables as predictors of long-term psychological status among the torture survivors. <h3>Setting.</h3> —Istanbul, Turkey. <h3>Main Outcome Measures.</h3> —Number of lifetime and current PTSD symptoms, and scores on the Beck Depression Inventory, Hamilton Depression Rating, Hamilton Anxiety Scale, and State-Trait Anxiety Inventory. <h3>Results.</h3> —Effect of captivity experience on various life areas (eg, family and social, economic, and employment status) and other postcaptivity psychosocial stressors were associated with PTSD symptoms, anxiety, and depression. Perceived severity of torture was related to PTSD symptoms but not to anxiety or depression. Lack of social support predicted anxiety and depression but not PTSD. Family history of psychiatric illness correlated with higher scores on most measures. Impact of captivity experience on family was the strongest predictor of PTSD symptoms. <h3>Conclusions.</h3> —These findings point to three types of stressors related to different aspects of psychopathology in survivors of torture: perceived severity of torture, secondary effects of captivity experience on various life areas, and general psychosocial stressors following captivity. Different interventions may be needed for three components of survivors' traumatic experience: cognitive and behavioral strategies for treatment of PTSD symptoms, marital or family strategies for minimizing the impact of the trauma on the family, and strategies for enhancing social support to minimize postcaptivity depression and anxiety. (<i>JAMA</i>. 1994;272:357-363)
Abstract P418: Trans Fats Consumption Linked to Higher BMI
Authors: Beatrice A Golomb, Hayley J Koslik
Journal: Circulation (2014)

Background: Increasing evidence suggests that factors beyond calorie balance may affect fat deposition (consider environmental obesogens like bisphenol A). Trans fats are prooxidant, proinflammatory, have shown adverse metabolic effects and increased fat deposition in animals. Goal: To assess the relation of dietary trans fatty acid ( dTFA ) consumption to BMI in humans. Method: Subjects were 1018 adult men and women clinical trial screenees (age 20-85, without known diabetes, CVD, with screening LDL 115-190mg/dL). Height and weight were measured at screening and BMI calculated. The Fred Hutchinson Food Frequency Questionnaire provided data on dTFA (gm/d) and calories. Surveys elicited activity, and chocolate consumption (times/week, previously linked favorably in this sample to BMI). Mood (adversely linked to dTFA in this sample and in literature) was assessed by the CES-D (depression scale). Regression assessed the relation of BMI (outcome) to dTFA, unadjusted and in models adjusted for age and sex, calories and activity, chocolate consumption, and mood. Results: Higher dTFA was linked with higher BMI across adjustment models, with strong statistical significance. The coefficient was strengthened, not attenuated, when calories and activity were considered. Each additional gram/day of dTFAs was associated with around 0.4 points greater BMI. Discussion: These findings extend adverse metabolic associations of dTFA, and comport with evidence suggesting that composition of calories, as well as their number, has relevance to BMI.
A controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer
Authors: Fadlo R. Khuri, John Nemunaitis, Ian Ganly, James Arseneau, Ian F. Tannock, Larry Romel, Martin Gore, Janet Ironside, R.H. MacDougall, Carla Heise, Britta Randlev, Ann M. Gillenwater, Patricia Bruso, Stanley B. Kaye, Waun Ki Hong, David H. Kirn
Journal: Nature Medicine (2000)
Management and outcome of patients undergoing surgery after acute upper gastrointestinal haemorrhage
Authors: T A Rockall
Journal: Journal of the Royal Society of Medicine (1998)

Most patients with acute upper gastrointestinal haemorrhage are managed conservatively or with endoscopic intervention but some ultimately require surgery to arrest the haemorrhage. We have conducted a population-based multicentre prospective observational study of management and outcomes. This paper concerns the subgroup of 307 patients who had an operation because of continued or recurrent haemorrhage or high risk of further bleeding. The principal diagnostic group was those with peptic ulcer. Of 2071 patients with peptic ulcer presenting with acute haemorrhage, 251 (12%) had an operative intervention with a mortality of 24%. In the non-operative group mortality was 10%. The operative intervention rate increased with risk score, ranging from 0% in the lowest risk categories to 38% in the highest. Much of the discrepancy between operative and non-operative mortality was explainable by case mix; however, for high-risk cases mortality was significantly higher in the operated group. In 78% of patients who underwent an operation for bleeding peptic ulcer there had been no previous attempt at endoscopic haemostasis. For patients admitted to surgical units, the operative intervention rate was about four times higher than for those admitted under medical teams. In patients with acute upper gastrointestinal haemorrhage operative intervention is infrequent and largely confined to the highest-risk patients. The continuing high mortality in surgically treated patients is therefore to be expected. The reasons for the low use of endoscopic treatment before surgery are not revealed by this study, but wider use of such treatments might further reduce the operative intervention rate. Physicians and surgeons have not yet reached consensus on who needs surgery and when.
Abstract 1556: Regulation of cellular apoptosis via a novel protein-protein interaction of tumor suppressor p53 with the xenobiotic pregnane X receptor (PXR) in colon cancer cells
Authors: Delira F. Robbins, Jing Wu, Taosheng Chen
Journal: Cancer Research (2014)

Abstract The cellular response to DNA damage comprises of DNA repair, cell-cycle checkpoint control and DNA damage-induced apoptosis to promote genomic integrity and suppress tumorigenesis. However, cancer cells can modulate the DNA damage response by suppressing DNA repair, altering cell cycle checkpoint control and ultimately downregulating tumor suppressors that contribute to apoptosis promoting genomic instability and avoidance of apoptosis. Although PXR is well established as a xenobiotic nuclear receptor that plays a central role in xenobiotic metabolism and disposition, emerging evidence suggest PXR as a regulator of apoptosis, promoting a malignant phenotype, both in vitro and in vivo. The tumor suppressor p53 can be activated in the presence of DNA damage and can induce cell cycle arrest to allow for DNA repair, or ultimately apoptosis suppressing tumor formation. We hypothesized that the novel protein-protein interaction between PXR and p53 contributes to the oncogenic functions of PXR enhancing colon carcinogenesis. Using immunoprecipitation, we found that PXR forms a protein-protein interaction with p53, resulting in reduced p53 activation and expression of downstream pro-apoptotic genes. In addition, utilizing the soft agar assay, we found that PXR overexpression leads to increased malignant transformation in colon cancer cells. Our findings show for the first time that PXR can physically bind to p53, resulting in downregulation of p53 activity and increased malignant transformation in colon cancer cells. Thus, these results provide insight into the biological significance of novel protein-protein interactions with PXR and how the PXR-p53 protein-protein interaction influences p53-mediated mechanism of tumor suppression. Citation Format: Delira F. Robbins, Jing Wu, Taosheng Chen. Regulation of cellular apoptosis via a novel protein-protein interaction of tumor suppressor p53 with the xenobiotic pregnane X receptor (PXR) in colon cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1556. doi:10.1158/1538-7445.AM2014-1556
Abstract 9652: Layer-specific Analysis of Myocardial Ischemic Memory Using Speckle Tracking Echocardiography
Authors: Daisuke Sakurai, Toshihiko Asanuma, Kasumi Masuda, Ayana Hioki, Satoshi Nakatani
Journal: Circulation (2011)

Background: Recently, speckle tracking echocardiography has allowed us to easily quantify not only regional myocardial but multilayer deformation. Post-systolic shortening (PSS) is a sensitive marker of myocardial ischemia and remains even after relief from brief ischemia (ischemic memory). However, differences of ischemic memory among the layers are unclear. The aim of this study was to evaluate ischemic memory of PSS-related parameters with multilayer analysis using speckle tracking echocardiography. Methods: In 9 open-chest dogs, left ventricular short-axis images were acquired at baseline, during occlusion of the left anterior descending coronary artery (2 min), and after reperfusion (10, 20, and 30 min). Circumferential strain profiles were analyzed in three layers (endocardial, mid-wall, and epicardial). Peak systolic strain (ε S ) and strain at aortic valve closure (ε AVC ) were measured. Post-systolic index (PSI) and time to peak strain (T P ) were calculated as parameters of PSS. Results: In all three myocardial layers, ε S and ε AVC decreased during occlusion compared with baseline, but these parameters returned to the baseline levels immediately after reperfusion. In the endocardial and mid-wall layers, PSI significantly increased during occlusion, and the increase remained until 20 min after reperfusion (Figure). T P also significantly increased until 20 min after reperfusion in both layers. On the other hand, in the epicardial layer, PSI and T P did not significantly change after reperfusion because PSS did not persist. Conclusion: With multilayer analysis using speckle tracking echocardiography, ischemic memory of PSS-related parameters remained longer in the endocardial and mid-wall layers than the epicardial layer. Layer-specific analysis may be useful for assessing ischemic memory.
Abstract 11138: Simplified Rheumatic Heart Disease Screening Criteria for Handheld Echocardiography
Authors: Jimmy C Lu, Craig Sable, Gregory J Ensing, Catherine C Webb, Janet Scheel, Twalib Aliku, Justin C Godown, Andrea Beaton
Journal: Circulation (2014)

Background: Using 2012 World Heart Federation (WHF) criteria, standard portable echocardiography (SPE) reveals a high burden of rheumatic heart disease (RHD) in resource poor settings, but widespread screening is limited by cost and physician availability. Handheld echocardiography (HHE) may decrease costs, but WHF criteria are complicated for rapid field screening, particularly for non-physician screeners. Objective: To determine the best simplified screening strategy for RHD detection using HHE. Methods: HHE (GE Vscan) and SPE (GE Vivid q or i or Philips CX-50) were performed in 5 schools in Gulu, Uganda. Borderline or definite RHD cases were defined by 2012 WHF criteria on SPE images, by 2 experienced readers. HHE studies were reviewed by cardiologists blinded to SP results. As HHE lacks continuous wave Doppler, pansystolic mitral regurgitation (MR) was defined as MR on 2 consecutive frames. We evaluated single and combined HHE parameters to determine the simplified screening strategy that maximized sensitivity and specificity for case detection. Results: In 1420 children (10.8±2.6 years old, 47% male) with HHE and SPE studies, morphologic criteria and presence of any MR by HHE had poor specificity (Table). MR jet length by HHE correlated with SPE (r=0.54, p&lt;0.0001). Aortic insufficiency (AI) was specific but not sensitive. Combined criteria of MR jet length ≥1.5 cm, chosen from receiver operating characteristic analysis, or any AI best balanced sensitivity and specificity; pansystolic MR could be substituted for MR jet length with slightly lower sensitivity for definite RHD. With a prevalence of 4% and subsequent SPE screening of positive HHE studies, this would reduce SPE studies by 80% from a SPE-based screening strategy. Conclusions: In resource-limited settings, HHE with simplified criteria offers reasonable sensitivity and specificity for RHD screening. Further study is needed to validate HH screening by local practitioners and long-term outcomes.
Abstract P270: Niacin Lowers Triglyceride-Rich Lipoprotein Apolipoprotein B-48 Secretion in Statin-Treated Type 2 Diabetics
Authors: Jing Pang, Dick Chan, Sandy Hamilton, Vijay Tenneti, Gerald Watts, Hugh Barrett
Journal: Circulation (2014)

Background: Type 2 diabetic subjects often have hypertriglyceridemia and an increased concentration of apolipoprotein B-48 (apoB-48) in circulation, particularly during the postprandial period. There is an accumulating body of evidence to suggest that apoB-48 plays a central role in the development of atherosclerosis. Statins are the frontline therapy to reduce cardiovascular risk, however, a large residual risk still remains. This residual risk suggests that additional therapeutic interventions may be required to further reduce CVD risk. Aim: To investigate the effect of niacin on the metabolism of triglyceride-rich lipoprotein (TRL) apoB-48 in men with type 2 diabetes on background statin therapy. Methods: Twelve type 2 diabetic men were recruited for this randomized, cross-over design study. Patients required a statin-treated low density lipoprotein (LDL) cholesterol of less than 2.5 mmol/L to enter the trial. Patients were then randomized to rosuvastatin alone or rosuvastatin plus niacin (titrated up from 1 to 2 g daily) for a period of 12 weeks and then were crossed over to the alternate therapy with a 3 week washout period in between. Metabolic studies were performed at the end of each treatment period. A bolus intravenous infusion of D3-leucine was administered as subjects consumed a standardised high-fat liquid meal. Blood samples were collected over 24 hours and TRL apoB-48 tracer/tracee ratios were measured using gas chromatography-mass spectrometry. Kinetic parameters, including fractional catabolic rate (FCR) and production rate (PR), were derived using a multicompartmental model. Results: Niacin significantly reduced triglyceride, plasma cholesterol, LDL cholesterol and apoB (all p&lt;0.005). TRL apoB-48 concentration was lower with niacin (8.24 ± 1.98 vs 5.48 ± 1.14 mg/L, p=0.03). ApoB-48 FCR was not altered with niacin (8.78 ± 1.04 vs 9.17 ± 1.26 pools/day; p=0.79). Basal apoB-48 PR (3.21 ± 0.34 vs 2.50 ± 0.31 mg/kg/day; p=0.04) and postprandial apoB-48 PR were significantly lower (1.35 ± 0.19 vs 0.84 ± 0.12 mg/kg; p=0.02) on niacin. Conclusion: Niacin reduces TRL apoB-48 concentration by lowering basal and postprandial apoB-48 PR. This effect on apoB-48 metabolism may be beneficial for reducing atherogenic postprandial TRL particles and may provide CVD risk benefit to patients with type 2 diabetes.
Abstract 13697: Glucagon-like Peptide-1 Analogue Liraglutide Does Not Improve Microvascular Myocardial Function in Patients With Type 2 Diabetes - a Randomized, Single-blinded Cross Over Trial
Authors: Rebekka Faber, Mette Zander, Adam A Pena, Marie M Michelsen, Naja D Mygind, Eva Prescott
Journal: Circulation (2014)

Background: Impaired coronary microcirculation is associated with a poor prognosis in patients with type 2 diabetes. In the absence of stenosis of major coronary arteries, coronary flow reserve (CFR) reflects coronary microcirculation. Studies have shown beneficial effects of glucagon-like peptide-1 (GLP-1) on the cardiovascular system. The aim of the study was to explore the short-term effect of GLP-1 treatment on coronary microcirculation estimated by CFR in patients with type 2 diabetes. Methods: Twenty patients with type 2 diabetes and no history of coronary artery disease were treated with the GLP-1 analogue Liraglutide for 10 weeks, in a randomized single-blinded crossover setup. The effect of GLP-1 on coronary microcirculation was evaluated using non-invasive trans-thoracic Doppler-flow echocardiography during dipyridamole induced stress. Data were analysed as two-sample t-test after ensuring no carry over effect. Results: A total of 20 patients (15 male; mean age 57 ± 9; mean BMI 33.1 ± 4.4, mean baseline CFR 2.35 ± 0.45) completed full protocol. There was a small increase in CFR following GLP-1 treatment (change 0.18, CI95% [-0.01; 0.36], p=0.06) but with no difference in effect compared with the no treatment group (0.16, CI95% [-0.08; 0.40], p=0.18). GLP-1 significantly reduced glycated haemoglobin (-10.1 mmol/mol CI95% [-13.9; -6.4], p=&lt;0.001) systolic blood pressure (-10 mmHg CI95% [-17; -3], p=0.01) and weight (-1.9 kg CI95% [-3.6; -0.2], p=0.03). Conclusion: Despite a significant weight-loss, reduction in HbA1c and systolic blood pressure, we did not find a significant improvement in coronary microcirculation after 10 weeks treatment with GLP-1. In our short-term treatment study, we therefore conclude that the GLP-1 analogue Liraglutide does not improve coronary microcirculation in patients with type 2 diabetes. Further long-term studies are needed to explore mechanisms to improve coronary microcirculation in patients with type 2 diabetes.
Abstract 487: The Integrated Stress Response kinase GCN2 regulates cell proliferation and survival through combined transcriptional and translational control of p21 (Cip1/Waf1)
Authors: Stacey L. Lehman, Jiangbin Ye, Constantinos Koumenis
Journal: Cancer Research (2014)

Abstract The tumor microenvironment is often characterized by deficiencies in nutrients, such as oxygen, glucose, and amino acids. Activation of the nutrient-sensing kinase GCN2, which constitutes one arm of the Integrated Stress Response (ISR), is one mechanism by which tumor cells cope with and adapt to nutrient stress. GCN2 phosphorylates the alpha subunit of eukaryotic translation initiation factor eIF2, leading to global downregulation of translation to conserve amino acids and initiation of a transcriptional program through ATF4 to promote recovery from nutrient deprivation. Loss of GCN2 results in decreased tumor cell survival in vitro under conditions of amino acid deprivation and attenuated tumor growth in vivo in a variety of implanted animal tumor models. Our recent studies have shown that amino acid deprivation induces the cell cycle inhibitor p21 in a GCN2-dependent manner. GCN2 regulates p21 at both the transcriptional and translational level. Upregulation of p21 results in cell cycle arrest and promotes survival under amino acid deprivation. In agreement with a pro-survival role, we observe p21 upregulation concomitant with ISR activation in a genetically engineered mouse model of soft tissue sarcoma. These findings point to a novel mechanism of p21 regulation in order to coordinate cell division with nutrient availability. Research supported by NCI R01CA094214. Citation Format: Stacey L. Lehman, Jiangbin Ye, Constantinos Koumenis. The Integrated Stress Response kinase GCN2 regulates cell proliferation and survival through combined transcriptional and translational control of p21 (Cip1/Waf1). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 487. doi:10.1158/1538-7445.AM2014-487
Impact of Body Weight and Extreme Obesity on the Presentation, Treatment, and In-Hospital Outcomes of 50,149 Patients With ST-Segment Elevation Myocardial Infarction
Authors: Sandeep R. Das, Karen P. Alexander, Anita Y. Chen, Tiffany M. Powell-Wiley, Deborah B. Diercks, Eric D. Peterson, Matthew T. Roe, James A. de Lemos
Journal: Journal of the American College of Cardiology (2011)