tbuckley/cabot-search huggingface dataset:
Activation of monocytes and platelets by monoclonal antibodies or malaria-infected erythrocytes binding to the CD36 surface receptor in vitro.
Authors: C F Ockenhouse, C Magowan, J D Chulay
Journal: Journal of Clinical Investigation (1989)

The CD36 leukocyte differentiation antigen, recognized by MAbs OKM5 and OKM8 and found on human monocytes and endothelial cells, has been implicated as a sequestration receptor for erythrocytes infected with the human malaria parasite Plasmodium falciparum (IRBC). CD36 is also expressed on platelets and appears to be identical to platelet glycoprotein IV. We investigated receptor activation of monocytes and platelets by anti-CD36 MAbs and by IRBC. Incubation of human monocytes with anti-CD36 MAbs or IRBC resulted in stimulation of the respiratory burst as measured by reduction of nitroblue tetrazolium and generation of chemiluminescence. Incubation of human platelets with anti-CD36 MAbs resulted in platelet activation as measured by aggregation or ATP secretion. Activation of monocytes and platelets required appropriate intracellular transmembrane signaling and was inhibited by calcium antagonists or by specific inhibitors of protein kinase C or guanine nucleotide binding proteins. Soluble CD36 inhibited binding of IRBC to both monocytes and platelets, suggesting that these interactions are mediated by the CD36 receptor. Using a cytochemical electron microscopic technique, the presence of reactive oxygen intermediates was identified at the interface between human monocytes and IRBC. These data provide support for the hypothesis that reactive oxygen intermediates produced by monocytes when IRBC ligands interact with cell surface receptors may play a role in the pathophysiology of falciparum malaria.
TWO YEAR FOLLOW-UP STUDY OF THE RELATIONSHIP OF CHLORPROMAZINE AND THE INCIDENCE OF CONVULSIONS IN FIFTY POST-LOBOTOMY PATIENTS
Authors: A. E. PAGANINI, M. ZLOTLOW
Journal: American Journal of Psychiatry (1958)

Our 2 year follow-up study of 50 post-lobotomy patients and the incidence of convulsions with chlorpromazine therapy reveals the following conclusions: 1. Chlorpromazine did not increase the frequency of convulsions in post-lobotomy patients who have a convulsive background. 2. In post-lobotomy patients who never had convulsions, chlorpromazine did not produce convulsions but the possibility of a "masked fit" in one case of sudden death must be entertained. 3. In patients who have a history of convulsions, the seizures seemed to occur within 2-4 weeks of the institution of therapy but the number of fits seems to be decreasing. This may indicate a probable synergistic action between the anti-convulsants and chlorpromazine. 4. Anti-convulsants should be continued while the patient is on chlorpromazine if there is a history of convulsions. 5. In our opinion, there is no contra-indication or risk in the use of chlorpromazine for the relief of psychotic symptoms in post-lobotomy patients providing convulsive patients are continued on anti-convulsants.
Ventricular Nucleic Acid and Protein Levels with Myocardial Growth and Hypertrophy
Authors: ARTHUR F. GRIMM, RYO KUBOTA, WILLIAM V. WHITEHORN
Journal: Circulation Research (1966)

The myocardial DNA, RNA, actomyosin, and total protein concentrations were determined in rat ventricles ranging between 251 and 1635 mg. Three phases of myocardial growth were evident. Phase 1 (ventricular weights less than 550 mg): DNA concentrations remained relatively constant with increasing ventricular weight. The increasing total DNA per ventricle suggests continuing mitotic activity. Phase 2 (ventricular weights between 550 and 1000 mg): total DNA per ventricle remained relatively constant; with ventricular growth there was a progressive decrease in DNA concentrations. This would be the phase of true myocardial hypertrophy. Phase 3: DNA concentrations continued to slowly decrease although the total DNA per ventricle increased. It would appear that this is the result of a renewed synthesis of DNA. In phases 1 and 2, the RNA concentrations progressively decreased, although the RNA/DNA ratio was increasing. This ratio appeared to reach its maximum value by the end of phase 2 and remain relatively constant in phase 3. Thus in phase 3, the concentrations of DNA and RNA simultaneously decreased to maintain this constant ratio. The ventricular total protein and ventricular actomyosin levels did not change over this range of ventricular weights.
Gene functionalities and genome structure in Bathycoccus prasinos reflect cellular specializations at the base of the green lineage
Authors: Hervé Moreau, Bram Verhelst, Arnaud Couloux, Evelyne Derelle, Stephane Rombauts, Nigel Grimsley, Michiel Van Bel, Julie Poulain, Michaël Katinka, Martin F Hohmann-Marriott, Gwenael Piganeau, Pierre Rouzé, Corinne Da Silva, Patrick Wincker, Yves Van de Peer, Klaas Vandepoele
Journal: Genome biology (2012)

Abstract Background Bathycoccus prasinos is an extremely small cosmopolitan marine green alga whose cells are covered with intricate spider's web patterned scales that develop within the Golgi cisternae before their transport to the cell surface. The objective of this work is to sequence and analyze its genome, and to present a comparative analysis with other known genomes of the green lineage. Research Its small genome of 15 Mb consists of 19 chromosomes and lacks transposons. Although 70% of all B. prasinos genes share similarities with other Viridiplantae genes, up to 428 genes were probably acquired by horizontal gene transfer, mainly from other eukaryotes. Two chromosomes, one big and one small, are atypical, an unusual synapomorphic feature within the Mamiellales. Genes on these atypical outlier chromosomes show lower GC content and a significant fraction of putative horizontal gene transfer genes. Whereas the small outlier chromosome lacks colinearity with other Mamiellales and contains many unknown genes without homologs in other species, the big outlier shows a higher intron content, increased expression levels and a unique clustering pattern of housekeeping functionalities. Four gene families are highly expanded in B. prasinos , including sialyltransferases, sialidases, ankyrin repeats and zinc ion-binding genes, and we hypothesize that these genes are associated with the process of scale biogenesis. Conclusion The minimal genomes of the Mamiellophyceae provide a baseline for evolutionary and functional analyses of metabolic processes in green plants.
Effects of activation on lipoprotein lipase secretion by macrophages. Evidence for autoregulation.
Authors: S R Behr, F B Kraemer
Journal: The Journal of Experimental Medicine (1986)

Lipoprotein lipase (LPL) activity was measured in the media of cultured mouse peritoneal macrophages that were isolated after the intraperitoneal injection of inflammatory agents in order to yield a variety of states of activation. Fully activated macrophages obtained from Corynebacterium parvum-injected mice secreted very low levels of LPL when compared to unstimulated macrophages, while inflammatory and primed macrophages had increased LPL secretion. When inflammatory macrophages were incubated with conditioned medium obtained from fully activated macrophages, LPL secretion decreased in a time- and dose-dependent fashion. The factor(s) secreted by fully activated macrophages that inhibited LPL secretion was shown to be thermolabile and distinct from tumor necrosis factor. These results demonstrate that activation dramatically alters macrophage LPL secretion.
Association of Race With Mortality and Cardiovascular Events in a Large Cohort of US Veterans
Authors: Csaba P. Kovesdy, Keith C. Norris, L. Ebony Boulware, Jun L. Lu, Jennie Z. Ma, Elani Streja, Miklos Z. Molnar, Kamyar Kalantar-Zadeh
Journal: Circulation (2015)

In the general population, blacks experience higher mortality than their white peers, attributed in part to their lower socioeconomic status, reduced access to care, and possibly intrinsic biological factors. Patients with kidney disease are a notable exception, among whom blacks experience lower mortality. It is unclear if similar differences affecting outcomes exist in patients with no kidney disease but with equal or similar access to health care.
Evaluation of Antitumoral Properties of the Protease Inhibitor Indinavir in a Murine Model of Hepatocarcinoma
Authors: Vincenzo Esposito, Emanuele Palescandolo, Enrico P. Spugnini, Vincenzo Montesarchio, Antonio De Luca, Irene Cardillo, Giancarlo Cortese, Alfonso Baldi, Antonio Chirianni
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Accumulating evidences show a higher incidence of hepatic neoplasm in HIV/hepatitis C virus (HCV)–coinfected individuals compared with HCV-monoinfected patients. Treatment with HIV-1 protease inhibitors inhibited cancer-promoted angiogenesis in HIV-infected patients affected by Kaposi sarcoma. We aimed to evaluate the antineoplastic potential activities of the protease inhibitor indinavir (Crixivan) in in vitro and in vivo hepatocarcinoma models. Experimental Design: We analyzed effects of indinavir on cell growth and invasiveness in Huh7 and SK-HEP-1 hepatocarcinoma cell lines and on in vivo tumor growth of the same cells in nude mice. Morphologic and molecular analyses on explanted tumors were carried out to evaluate vascularization and apoptosis. Results: We observed a reduced ability to invade an in vitro extracellular matrix for both cell lines treated with indinavir compared with controls (P = 0,001). Moreover, indinavir treatment was able to inhibit matrix metalloproteinase-2 proteolytic activation, whereas there was no effect on cell proliferation. The drug was also able to delay in vivo tumor growth. The inhibition of tumor growth was statistically significant from days 6 to 21 (P = 0.004 and P = 0.003, respectively). Moreover, the drug showed antiangiogenic and proapoptotic actions, as revealed by vessel count and apoptotic index by terminal deoxynucleotide transferase–mediated nick end labeling in explanted tumors. Finally, treatment with indinavir did not block the production of vascular endothelial growth factor in the tumors. Conclusion: Indinavir could be helpful to prevent the development of hepatocarcinomas in HIV/HCV–coinfected individuals. In view of the current trend to substitute protease inhibitors with other antiretroviral agents, this information may have clinical implications.
Epigenetic variability in cells of normal cytology is associated with the risk of future morphological transformation
Authors: Andrew E Teschendorff, Allison Jones, Heidi Fiegl, Alexandra Sargent, Joanna J Zhuang, Henry C Kitchener, Martin Widschwendter
Journal: Genome Medicine (2012)

Recently, it has been proposed that epigenetic variation may contribute to the risk of complex genetic diseases like cancer. We aimed to demonstrate that epigenetic changes in normal cells, collected years in advance of the first signs of morphological transformation, can predict the risk of such transformation.We analyzed DNA methylation (DNAm) profiles of over 27,000 CpGs in cytologically normal cells of the uterine cervix from 152 women in a prospective nested case-control study. We used statistics based on differential variability to identify CpGs associated with the risk of transformation and a novel statistical algorithm called EVORA (Epigenetic Variable Outliers for Risk prediction Analysis) to make predictions.We observed many CpGs that were differentially variable between women who developed a non-invasive cervical neoplasia within 3 years of sample collection and those that remained disease-free. These CpGs exhibited heterogeneous outlier methylation profiles and overlapped strongly with CpGs undergoing age-associated DNA methylation changes in normal tissue. Using EVORA, we demonstrate that the risk of cervical neoplasia can be predicted in blind test sets (AUC = 0.66 (0.58 to 0.75)), and that assessment of DNAm variability allows more reliable identification of risk-associated CpGs than statistics based on differences in mean methylation levels. In independent data, EVORA showed high sensitivity and specificity to detect pre-invasive neoplasia and cervical cancer (AUC = 0.93 (0.86 to 1) and AUC = 1, respectively).We demonstrate that the risk of neoplastic transformation can be predicted from DNA methylation profiles in the morphologically normal cell of origin of an epithelial cancer. Having profiled only 0.1% of CpGs in the human genome, studies of wider coverage are likely to yield improved predictive and diagnostic models with the accuracy needed for clinical application.The ARTISTIC trial is registered with the International Standard Randomised Controlled Trial Number ISRCTN25417821.
Patterns of Functional Decline at the End of Life
Authors: June R. Lunney, Joanne Lynn, Daniel J. Foley, Steven Lipson, Jack M. Guralnik
Journal: JAMA (2003)

Clinicians have observed various patterns of functional decline at the end of life, but few empirical data have tested these patterns in large populations.To determine if functional decline differs among 4 types of illness trajectories: sudden death, cancer death, death from organ failure, and frailty.Cohort analysis of data from 4 US regions in the prospective, longitudinal Established Populations for Epidemiologic Studies of the Elderly (EPESE) study. Of the 14 456 participants aged 65 years or older who provided interviews at baseline (1981-1987), 4871 died during the first 6 years of follow-up; 4190 (86%) of these provided interviews within 1 year before dying. These decedents were evenly distributed in 12 cohorts based on the number of months between the final interview and death.Self- or proxy-reported physical function (performance of 7 activities of daily living [ADLs]) within 1 year prior to death; predicted ADL dependency prior to death.Mean function declined across the 12 cohorts, simulating individual decline in the final year of life. Sudden death decedents were highly functional even in the last month before death (mean [95% confidence interval [CI]] numbers of ADL dependencies: 0.69 [0.19-1.19] at 12 months before death vs 1.22 [0.59-1.85] at the final month of life, P =.20); cancer decedents were highly functional early in their final year but markedly more disabled 3 months prior to death (0.77 [0.30-1.24] vs 4.09 [3.37-4.81], P<.001); organ failure decedents experienced a fluctuating pattern of decline, with substantially poorer function during the last 3 months before death (2.10 [1.49-2.70] vs 3.66 [2.94-4.38], P<.001); and frail decedents were relatively more disabled in the final year and especially dependent during the last month (2.92 [2.24-3.60] vs 5.84 [5.33-6.35], P<.001). After controlling for age, sex, race, education, marital status, interval between final interview and death, and other demographic differences, frail decedents were more than 8 times more likely than sudden death decedents to be ADL dependent (OR, 8.32 [95% CI, 6.46-10.73); cancer decedents, one and a half times more likely (OR, 1.57 [95% CI, 1.25-1.96]); and organ failure decedents, 3 times more likely (OR, 3.00 [95% CI, 2.39-3.77]).Trajectories of functional decline at the end of life are quite variable. Differentiating among expected trajectories and related needs would help shape tailored strategies and better programs of care prior to death.
Couples of significant others (COSO) in a joint effort to quit smoking are more successful in achieving and maintaining abstinence
Authors: Aikaterini Tsoutsa, Ioanna Nikoloutsou, Theodoros Vassilakopoulos, Spyridon Zakynthinos, Paraskevi Katsaounou
Journal: European Respiratory Journal (2012)

Motivational support is crucial in the success of the smoking cessation. Significant others are a proven source of that support. As far as we know social support has been used to achieve smoking cessation higher rates, but only as support and not as a concurrent attempt of a couple to quit smoking. We investigated whether the inclusion of  of significant others in a joint effort to quit smoking in smoking cessation groups formed by a population based sample of participants would increase their succession rate compared to the participants that receive the same treatment alone. This was a randomized population-based intervention study at the smoking cessation clinic of Evangelismos hospital. We monitored for people that are related in the initial screening stage. Couples included life partners, family members or very close friends. Smokers were in all motivational stages. All participants underwent the same intervention with motivational and behavioural components in the smoking cessation groups and received medical consultation and pharmacotherapy (Varenicline). We compared so far the smoking cessation rates of 25 couples and 50 randomized smokers that followed our smoking cessation programme.  We found that participants that joint the COSO quit smoking in a higher rate (58%) than of smokers (38%). Within the dyad the person more motivated to quit smoking was usually the first to quit. Among  that quit smoking, men were more successful (63%) than women (49%).  We conclude that higher smoking cessation rates were obtained in COSO joining our smoking cessation program.
Conceptual Approaches to the Study of Health Disparities
Authors: Ana V. Diez Roux
Journal: Annual Review of Public Health (2012)

Scientific and policy interest in health disparities, defined as systematic, plausibly avoidable health differences adversely affecting socially disadvantaged groups, has increased markedly over the past few decades. Like other research, research in health disparities is strongly influenced by the underlying conceptual model of the hypothetical causes of disparities. Conceptual models are important and a major source of debate because multiple types of factors and processes may be involved in generating disparities, because different disciplines emphasize different types of factors, and because the conceptual model often drives what is studied, how results are interpreted, and which interventions are identified as most promising. This article reviews common conceptual approaches to health disparities including the genetic model, the fundamental cause model, the pathways model, and the interaction model. Strengths and limitations of the approaches are highlighted. The article concludes by outlining key elements and implications of an integrative systems-based conceptual model.
Caffeine Increases Ambulatory Glucose and Postprandial Responses in Coffee Drinkers With Type 2 Diabetes
Authors: James D. Lane, Mark N. Feinglos, Richard S. Surwit
Journal: Diabetes Care (2008)

Recent laboratory studies demonstrated that caffeine exaggerates glucose and insulin responses to standardized carbohydrate loads in habitual coffee drinkers who have type 2 diabetes (1–3). Similar postprandial effects in everyday life could disrupt clinical efforts to maintain glucose control in patients with type 2 diabetes. The aim of this study was to examine the effects of a moderate dose of caffeine on glucose levels and postprandial glucose responses in free-living coffee drinkers with type 2 diabetes. We specifically predicted that caffeine administration would increase glucose concentrations during the day and exaggerate the glucose increases that followed meals when habitual coffee drinkers with type 2 diabetes were monitored during everyday life.

The research protocol, approved by the Duke University Health Systems institutional review board, employed a double-blind crossover design to compare the effects of a moderate dose of caffeine (500 mg/day) with that of a placebo control. Subjects completed informed consent before testing and received $150.00 in compensation. The study group included 10 habitual coffee drinkers (five men and five women) who drank brewed coffee daily. All had at least a 6-month history of type 2 diabetes managed by a stable regimen of diet, exercise, and oral agents but no exogenous insulin. Subjects were free of major medical disorders, were …
Multidisciplinary Care in Cancer: The Fellowship of the Ring
Authors: Frances M. Boyle, Emma Robinson, Stewart M. Dunn, Paul C. Heinrich
Journal: Journal of Clinical Oncology (2005)

A young woman with advanced breast cancer came with her husband for a follow-up appointment after completing eight cycles of combination chemotherapy and trastuzumab on a clinical trial. Her scans revealed a complete response to therapy, but toxicity had been significant: she had lost her hair and a lot of weight. When I commented on her suffering, she responded that she had been to see Return of the King (the third movie in The Lord of the Rings trilogy), and she felt she had developed a “Gollum look.” Pulling off her hat, she revealed three long strands of hair over her bald scalp and thin face. The resemblance to the films’ pitiable character was indeed striking. When I asked if this was how she was feeling, she laughed, “No, I’m Frodo after destroying the ring in Mount Doom, and the eagles have just swept down to carry Sam and I to safety. We’re not sure yet where we are going, but it’s got to be better than where we have been.” We reflected for a while on what made the difference between the experience of carrying the burden of the ring (as she had identified the cancer) for Gollum and Frodo. Her response was unequivocal. Gollum had done it all by himself and had been destroyed in the process. Frodo, on the other hand, had been supported by Sam and the Fellowship—a combination of professional and intimate caregivers—and had lived to tell the tale.
Diabetes Mellitus, Aortic Stiffness, and Cardiovascular Mortality in End-Stage Renal Disease
Authors: TETSUO SHOJI, MASANORI EMOTO, KAYO SHINOHARA, RYUSUKE KAKIYA, YOSHIHIRO TSUJIMOTO, HIROSHI KISHIMOTO, EIJI ISHIMURA, TSUTOMU TABATA, YOSHIKI NISHIZAWA
Journal: Journal of the American Society of Nephrology (2001)

Cardiovascular mortality is elevated in patients with end-stage renal disease (ESRD), especially in those with diabetes mellitus. Although the higher cardiovascular death rate in diabetic ESRD patients may be the result of more advanced atherosclerotic changes of the arterial wall, this has not been documented previously. Aortic stiffness was compared between ESRD patients with and without diabetes, and the impact of aortic stiffness on cardiovascular mortality was examined in a prospective, observational cohort study. The cohort consisted of 265 ESRD patients on hemodialysis, including 50 diabetic patients studied between June 1992 and December 1998. At baseline, the diabetic ESRD patients had significantly higher aortic pulse wave velocity (PWV), a noninvasive measure of aortic stiffness, than the nondiabetic patients. During a mean follow-up period of 63 mo, 81 deaths, including 36 cardiovascular deaths, were recorded. Kaplan-Meier analysis revealed higher all-cause or cardiovascular mortality rates in the diabetic as compared with the nondiabetic patients and also in those with higher aortic PWV than those with lower aortic PWV. The effect of diabetes on cardiovascular death was significant in the Cox model, including age, years on hemodialysis, gender, smoking, C-reactive protein, hematocrit, and body mass index as covariates. However, when aortic PWV was included as a covariate, the impact of diabetes was no longer significant, whereas aortic PWV was a significant predictor. In a model including 13 covariates, aortic PWV remained a significant predictor for cardiovascular and overall mortality but not for non-cardiovascular death. These results demonstrate that the increased aortic stiffness of the ESRD patients with diabetes mellitus contributed to the higher allcause and cardiovascular mortality rates.