tbuckley/cabot-search huggingface dataset:
Renal Tubular Transport of Organic Acids
Authors: E. J. Weinman, S. J. Frankfurt, A. Ince, S. Sansom
Journal: Journal of Clinical Investigation (1978)

The renal handling of oxalate was examined by free-flow micropuncture, intratubular microinjection, and droplet precession techniques in the rat. After the sustained i.v. infusion of [14C]oxalate, the fractional delivery of oxalate from the early portions of the proximal tubule was 120.1±4.4%, indicating net secretion. Fractional delivery rates from the late proximal tubule (124.6±6.1), distal tubule (120.9±2.9), and final urine (126.2±2.9%) were not different from that of the early proximal tubule. Direct intratubular microinjections of oxalate into the early proximal tubule and late proximal tubule yielded urinary recovery rates of 85±3% and 101±2%, respectively, suggesting that oxalate absorption does occur in the mid-portions of the proximal tubule. Droplet precession studies confirmed a secretory flux for oxalate. In contrast to oxalate, para-aminohippurate (PAH), the more traditional marker for organic acid transport, was secreted in the late portions of the proximal tubule and in large measure at a site between the late proximal and distal tubules, presumably the pars recta. Probenecid inhibited PAH secretion but was without effect on net oxalate transport, oxalate absorption, or oxalate secretion.
Incorporating targeted therapy into conditioning regimen for patients undergoing autologous stem cell transplant (ASCT) for aggressive CD20 positive B-cell lymphoma has altered the natural history of the disease: A multivariate analysis of the prognostic factors
Authors: M. Farhat, I. Metzner, S. A. Gregory, P. Venugopal, M. Kassar, R. Karmali, J. Maciejewski, H. C. Fung
Journal: Journal of Clinical Oncology (2008)

19510 Background: ASCT has been typically used for patients with relapsed aggressive non-hodgkin lymphoma(NHL) with most treatment failures occuring within 1 to 2 years of transplant. We hypothesized that incorporating Rituximab to standard conditioning regimen such as BEAM (carmustine, cytarabine, etoposide, and melphalan) may have altered the natural history of aggressive NHL after ASCT irrespective of several prognostic factors Methods: A retrospective analysis from a single institution of 40 patients all with NHL (35 diffuse large cell lymphoma, 4 mantle cell lymphoma and 1 Burkitt lymphoma), 28 men and 12 women, with a median age at ASCT of 57 yrs (42 to 73), a median time to ASCT of 19.2 month, with a median of 2 chemotherapeutic treatment (1 to 7) prior to ASCT between September 1998 to July 2006. 14 patients received BEAM and 26 patients had R-BEAM. An actuarial rate for DFS and OS was estimated from the day of ASCT using a Kaplan-Meier method and a multivariate analysis using Cox regression model comparing R-BEAM to BEAM, correcting for age at transplant, number of therapy prior to transplant and time from diagnosis to transplant. Results: Median follow up of 14.5 month, 6/26 (23%) and 10/14 (71%) patients who received R-BEAM and BEAM respectively had relapse/progressive disease. The 2-years DFS were 70% and 31% for the R-BEAM and BEAM respectively (p=0.0013). The 2 years OS were 91% and 70% for the R-BEAM and BEAM respectively. A multivariate analysis looking at DFS and OS showed a hazard ratios of 0.51(p=0.027) and 0.52 (p=0.048) respectively favoring the R-BEAM group. Conclusions: Rituximab has proven itself to be beneficial in improving DFS and OS in aggressive NHL. Furthermore, the benefit was present and statistically significant irrespective of the multiple prognostic factors. Our study suggested that incorporating targeted immunotherapy into standard conditioning regimen improved the transplant outcomes in a multi-variate analysis and should be considered for all patients undergoing an ASCT for relaplse/refractory aggressive NHL. No significant financial relationships to disclose.
Abstract 8672: Neutrophil-to-Lymphocyte Ratio Predicts Prognosis in Patients with Chronic Coronary Heart Disease
Authors: Daniele Rovai, Francesco Sbrana, Franca Cocci, Angela Papa, Patrizia Landi, Antonio L'Abbate, Giuseppe Rossi
Journal: Circulation (2011)

Purpose: A relationship between blood cell count and survival has been observed both in healthy individuals and in patients with stable angina, unstable angina, myocardial infarction or heart failure. We tested the hypothesis that a complete blood count with subfraction concentrations would provide prognostic information in patients with chronic coronary heart disease (CHD), and that this information is additive to a standard diagnostic work-up. Methods: We prospectively examined 2370 consecutive patients with chronic CHD, defined by a &gt; 50% stenosis at coronary angiography and/or history of myocardial infarction (MI). We examined the association between complete blood count, clinical variables and future cardiac events (cardiac death and non-fatal MI). Results: During follow-up (median 46 months), 147 patients (6.2%) died of cardiac causes and 81 (3.4%) experienced a non-fatal MI. Using univariate analysis, reduced hematocrit (&lt; 36% if male and &lt; 40% if female) and a neutrophil-to-lymphocyte (N/L) ratio &gt; 2.42, but not white blood cell count and platelet count, were significantly associated with a reduced cardiac event-free survival (P &lt; 0.001 and P &lt; 0.0001, respectively). The impact of anemia and high N/L ratio on survival persisted after adjustment for age, diabetes mellitus, left ventricular ejection fraction and angiographic extent of coronary atherosclerosis. The negative prognostic impact of a high N/L ratio persisted even after adjustment for both clinical variables and other routine laboratory variables (risk ratio: 1.57, 95% confidence interval: 1.19 to 2.08, p = 0.0014). Conclusion: An elevated N/L ratio is a significant predictor of adverse prognosis in patients with chronic CHD.
Long-Term Molecular Results Of The Gimema VEL-03-096 Trial: Molecular Remission Achievement and Loss Are Major Outcome Predictors
Authors: Simone Ferrero, Marco Ladetto, Daniela Drandi, Federica Cavallo, Elisa Genuardi, Marina Urbano, Guglielmo Guarona, Vincenzo Callea, Clotilde Cangialosi, Tommaso Caravita, Claudia Crippa, Luca De Rosa, Antonietta Pia Falcone, Mariella Grasso, Tommasina Guglielmelli, Anna Marina Liberati, Francesco Pisani, Patrizia Pregno, Fausto Rossini, Stefania Oliva, Alberto Rocci, Roberto Passera, Mario Boccadoro, Antonio Palumbo
Journal: Blood (2013)
Suicidality, depression, and substance abuse in adolescence
Authors: J C Levy, E Y Deykin
Journal: American Journal of Psychiatry (1989)

The authors assessed the occurrence of suicidal ideation, suicide attempts, major depression, and substance abuse in a sample of 424 apparently healthy college students 16-19 years old. Major depression and substance abuse were independent and interactive risk factors for suicidal ideation and for suicide attempts; substance abuse had a particularly deleterious effect on men. A prolonged desire to be dead was a more specific risk factor for a suicide attempt than was a thought of suicide. The authors conclude that suicidal ideation in the presence of major depression and/or substance abuse in older adolescents should call forth greater concern for lethality.
Abstract P080: The Combined Effect of Low Income and Low Education on Coronary Heart Disease Outcomes in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study
Authors: Marquita W Lewis, Yulia Khodneva, Monika M Safford
Journal: Circulation (2015)

Background: Low income (LoINC) and low education (LoED) have both been associated with higher coronary heart disease (CHD) risk, but few studies have examined the combined effects of both LoINC and LoED. Hypothesis: The combination of LoINC and LoED is more strongly associated with incident CHD than either LoINC and LoED, or neither. Methods: REGARDS recruited 30,239 black and white participants aged &gt; 45 years residing in the 48 contiguous US between 2003-2007. Baseline data included telephone interviews and in-home visits, and follow-up was conducted every 6 months to detect potential events with expert adjudication of endpoints based on medical record review. Low income (LoInc) was defined as annual household income &lt;$35,000, and low education (LoEd) was defined as less than a high school education. Income and education were combined into four mutually exclusive exposure groups (noLoInc+noLoEd, noLoInc+LoEd, LoInc+noLoEd ,LoInc+LoEd, ). CHD outcomes were definite or probable myocardial infarction or acute CHD death. We constructed Cox models estimating the hazard ratios (HR) for CHD, sequentially adjusting for sociodemographics, health behaviors, physiologic parameters, access to healthcare, and stress and depression. Because of significant interaction by age (p&lt;0.001), analyses were stratified at age 65. Results: We analyzed 24,461 participants without baseline CHD, with numbers in each income/education group as shown in the Table. LoInc+LoEd was associated with the highest risk of CHD among those aged &lt; 65 years, but not among those &gt;65 years of age. LoEd was associated with higher CHD risk in those age &gt;65 years and LoInc was not, but LoInc was associated with higher CHD risk in those age &lt; 65 years, but LoEd was not. Conclusion: LoInc+LoEd was associated with the highest CHD risk at younger ages, but not at higher ages. Income was more important than education for CHD risk at younger ages, but education was more important than income at older ages.
CATALASE ACTIVITY IN MOUSE LEUKEMIA L1210.
Authors: Fredrik I. Lottsfeldt, Carole Pehoushek, William Krivit
Journal: Cancer Research (1965)

Serial determinations of liver, kidney, spleen, and blood catalase were made on BDF1 mice with leukemia L1210. Total liver catalase was significantly decreased in the terminal stage of the disease. Spleen catalase specific activity was significantly increased in the terminal stage. Kidney and blood catalase were unchanged. In leukemic mice treated with amethopterin, the same changes in catalase occurred, but at a delayed rate. After prolonged therapy, kidney catalase was also depressed.
Abstract 14429: High Pulse Pressure is Associated With Reduced Gait Speed in Community-Dwelling Older Adults: Findings From the Life-P Study
Authors: Kevin S Heffernan, Todd M Manini, Steven N Blair, Timothy S Church, Stephen B Kritchevsky, Barbara J Nicklas, Kimberly Sutton-Tyrell, Fang-Chi Hsu, Jeffrey T Kuvin, Richard H Karas, William L Haskell, Roger A Fielding
Journal: Circulation (2010)
STUDIES ON THE EFFECT OF CARDIAC IRREGULARITY ON THE CIRCULATION
Authors: Harold J. Stewart, J. Hamilton Crawford, A. R. Gilchrist
Journal: Journal of Clinical Investigation (1928)

In preceding papers (1, 2) we have reported observations concerning the effect of regular and irregular tachycardia (auricular fibrillation) on the rate of blood flow in normal unanesthetized dogs.The terms "rate of blood flow" and "relative blood flow" have been used in these investigations (1, 2) to denote specific functions.The rate ofbloodflow refers to the arterio-venous difference in oxygen.The difference corresponds to the tissue utilization of this gas.The vol- ume of gas which the tissues take depends of course on the volume of blood which passes them.If their requirements (that is to say, metabolism) remain constant, the amount of oxygen taken must re- main constant, provided that the volume of the blood and the partial pressure of the gases in it, also remain constant.We infer that if the arterio-venous difference changes, either by increase or by diminution, the volume of blood which passes the tissues must have changed, for there is no reason to believe that there has been change in any of the other possible factors.Obviously, the data do not permit definitive inferences to be drawn on the cardiac output, for we lack knowledge in these experiments of the amount of oxygen which has been breathed.O1; We have taken in a given animal, the arterio-venous difference to represent 100, when the mechanism of his heart beat is normal.We have also estimated it under the conditions developed by various abnormal rhythms and have found a ratio between the normal and the abnormal figures.This ratio we call relative blood flow.If, for SUMMARY The rate of blood flow and pulse deficit have been correlated in artifically induced regular and irregular tachycardia in normal un- anesthetized dogs.It was found that:1.During rapid auricular fibrillation the rate of blood flow was decreased and a pulse deficit was present.
Abstract 3385: Cardiac Stem Cell Survival During DNA Damage Is Regulated By Modulation Of Histone Acetyl Transferase p300
Authors: Sumit Jain, Claudia Rodrigues, Huijun Yuan, Jing Liu, Keith A Webster, Nanette H Bishopric
Journal: Circulation (2008)

Background: Many sources of oxidative stress, including ischemia/reperfusion and chemotherapy, can induce DNA damage in the heart, leading to loss of cardiomyocytes and development of heart failure. Cardiac stem cells (CSCs) may serve to regenerate injured myocardium. However, ischemic injury has been associated with senescence and apoptosis in CSCs, potentially limiting their contribution to tissue repair. The histone acetyltransferase p300 has been shown to be an important regulator of genome stability and is involved in cell survival in response to DNA damage. We hypothesized that p300 could play a role in CSC response to oxidant stress. Methods: c-kit+, sca-1+ CSCs were isolated and cloned by serial dilution from adult mouse hearts. CSC clones were stably transfected with lentivirus vectors carrying shRNAmir against p300 or a non-silencing RNA (NS) and maintained under puromycin selection prior to treatment. CSCs were exposed to doxorubicin (DOX), a DNA-damaging agent, for defined intervals. Levels of p300 were monitored by Western analysis and expression of DNA damage-regulated genes was assessed using multiplex realtime QPCR. CSCs were treated with 1 uM DOX and survival was assessed over a period of 72h. Results: Levels of p300 increased rapidly in CSCs within 4h after exposure to doxorubicin and were sustained for at least 24h. CSCs expressing p300 shRNAmir (p300 KD) contained ~20% of the amount of p300 in CSCs transfected with the NS sequence (NS CSCs). QPCR analysis of DNA repair and cell cycle control genes indicated that 44 were significantly expressed in CSCs; 13 of these were up-regulated by p300 loss, and 5 were down-regulated, indicative of a DNA damage response to p300 loss. Both cell proliferation rates and progression through the cell cycle were slower in p300 KD vs. NS CSCs. Surprisingly, following 48h treatment with DOX, p300 KD CSCs had 32% improved survival vs. NS CSCs. Conclusions: Under acute genotoxic stress, p300 accumulates in CSCs. Reducing p300 levels induces the expression of genes involved in the DNA damage response, probably as a compensatory response, and slows CSC proliferation. Loss or inhibition of p300 is likely to cause multifactorial growth arrest in CSCs and thereby reduce their vulnerability to genotoxic agents. This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract MP94: Impact of a 12-Weeks Supervised Physical Activity Program After Bariatric Surgery on Body Composition and on Abdominal and Mid-Thigh Body Fat Distribution Changes; a Randomized Study
Authors: Audrey Auclair, Jany Harvey, Alexandre Sanctuaire, Simon Marceau, Laurent Biertho, Simon Biron, Frederic-Simon Hould, Stefane Lebel, Odette Lescelleur, Paul Poirier
Journal: Circulation (2015)

Bariatric surgery is the most effective long-term treatment for the management of severe obesity. Weight loss induced by bariatric surgery is characterize by a greater reduction of fat mass but als...
The Campbell Collaboration
Authors: P. Davies, R. Boruch
Journal: BMJ (2001)

Aim: Minichromosome maintenance (MCM) proteins are involved in initiation of DNA replication and cell-cycle progression. Loss of MCM function results in genomic instability and causes carcinogenesis. Among MCM genes, the role and prognostic value of MCM6 expression in clear-cell renal cell carcinoma (ccRCC) has not been elucidated. Materials and Methods: We assessed the mRNA expression level of MCM6 using the Gene Expression Profiling Interactive Analysis database and investigated MCM6 protein expression by immunohistochemistry in 238 ccRCC cases. Results: High MCM6 expression was significantly associated with increasing tumor size, pT, stage, tumor necrosis, and metastasis. Furthermore, high MCM6 expression was significantly associated with shorter overall and disease-free survival, and was an independent unfavorable prognostic marker. Regarding patients with metastasis, high MCM6-expressing ccRCC conferred significantly shorter survival than for those with low expression. Conclusion: A high MCM6 expression level may be a promising biomarker to predict tumor progression, metastasis, and survival in patients with ccRCC.
Abstract P070: Comparison of Heritability Estimation Using the Principal Components Calculated by Maximizing Variance and Heritability for OSA Traits
Authors: Jingjing Liang, Tao Feng, Brian Cade, Xihong Lin, Richa Saxena, Kevin Gleason, Xiaofeng Zhu, Susan Redline
Journal: Circulation (2015)

RATIONALE: Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive pauses in breathing during sleep associated with significant cardiovascular morbidity. Accumulating study results suggest that there are strong genetic contributions for this disease as defined by the apnea hypopnea index (AHI), the number of breathing pauses per hour of sleep. Using this metric, it has been shown that OSA significantly aggregates within families (1-2); heritability for the AHI is estimated to vary from about 20 to 40% (2-3). However, the AHI is only one index from several that describe OSA severity, and may not be the most relevant phenotype for genetic studies. It has not, however, been clear how to systematically assess heritability of multiple correlated and uncorrelated OSA traits. METHODS: To identify OSA related phenotypes that are most heritable to inform discovery of genetic risk variants for the disease, heritability analysis of multiple OSA related phenotypes were conducted using family data from Cleveland Family Study which comprises 700 African Americans from 147 families and 669 European Americans from 139 families. Principal-components analysis was performed using two approaches for combining data for six OSA traits that describe several dimensions of physiological and clinical impairment: the AHI and three other sleep study metrics (average hypopnea duration, average oxygen saturation, and percent time at oxygen saturation of &lt; 90%) and two OSA symptoms (habitual snoring and excessive sleepiness). One method uses the traditional principal-components (PC) approach assuming all subjects are independent. The other developed by Rabinowitz and Ott (4) calculates principal components by maximizing the heritability. RESULTS: In European Americans, the maximum heritability for the traditional multi-trait PC was 0.513 (SE=0.1010) while it was 0.512 (SE=0.100) for the PC calculated maximizing heritability. The maximum individual trait heritability was for average oxygen saturation, which is 0.388 (SE=0.107). In African Americans, the maximum heritability of traditional multi-trait 0.50 (SE=0.094) while it was 0.616 (SE=0.091) for the PC calculated maximizing heritability. The maximum individual trait heritability was for average hypopnea duration, which is 0.570 (SE=0.096). CONCLUSIONS: In general, both principal components approaches (maximizing variance and heritability) of six OSA related traits result higher heritability estimates than individual trait heritability estimates. The principal components approach based on maximizing heritability has the potential to improve trait heritability and therefore can be useful in future association analysis for searching genes underlying obstructive sleep apnea.
Abstract 4757: Attenuated Plaque Identified by Intravascular Ultrasound Predicts No-Reflow After Stenting in Acute Myocardial Infarction: The HORIZONS-AMI Trial
Authors: Xiaofan Wu, Akiko Maehara, Gary S Mintz, Alexandra J Lansky, Bernhard Witzenbichler, Giulio Guagliumi, Bruce Brodie, Mirle A Kellett, Helen Parise, Roxana Mehran, Gregg W Stone
Journal: Circulation (2009)

Background: Observational studies have suggested that attenuated plaques identified by grayscale intravascular ultrasound (IVUS) may predict transient deterioration in flow during percutaneous coronary intervention (PCI). If so, this phenomenon would be expected to be noted in pts undergoing primary PCI for STEMI. Methods and Results: We analyzed clinical, angiographic and IVUS characteristics of infarct related arteries of 365 stented pts from the randomized HORIZONS-AMI trial. No-reflow was defined as final TIMI grade 0, 1 or 2 flow in the absence of a mechanical obstruction on the post-PCI angiogram. Attenuated plaque was defined as hypoechoic or mixed atheroma with ultrasound attenuation without calcification. A mean attenuation score was created by measuring the angle of attenuation each 1mm, scoring as 1, 2, 3, or 4 when the angle was &lt;90°, 90 –180°, 180–270°, or 270–360°, respectively, then summing the scores and normalizing for analysis length. 77.8% pts had attenuated plaques, and no-reflow occurred in 10.1%. Pts with no-reflow more often had PCI of a LAD than non LAD (59.5% vs 36.9%, P =0.03) and had a higher mean attenuation score (median [95%CI]=2.2 [0, 2.8] vs 1.3 [0.6, 1.8], P&lt;0.001). There were no differences in baseline thrombus area, IVUS plaque burden, echolucent plaque, and stent expansion between pts with vs without no-reflow. The mean attenuation score that best predicted no-reflow was ≥2 (90–180°), with a sensitivity of 81.5% and a specificity of 80.5%. Conclusions: Attenuated plaque is present in three-quarters of pts with AMI, PCI of which is strongly correlated with no reflow. The larger the attenuated plaque, the greater the likelihood of no-reflow. Figure Attenuation angle: 125° Attenuation score: 2 points
Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk
Authors: Qi Zhu, Ji-Wang Zhang, Hai-Qing Zhu, Yu-Lei Shen, Maria Flexor, Pei-Ming Jia, Yun Yu, Xun Cai, Samuel Waxman, Michel Lanotte, Sai-Juan Chen, Zhu Chen, Jian-Hua Tong
Journal: Blood (2002)