tbuckley/cabot-search huggingface dataset:
Short- and Long-Term Clinical Outcome After Drug-Eluting Stent Implantation for the Percutaneous Treatment of Left Main Coronary Artery Disease
Authors: Marco Valgimigli, Carlos A.G. van Mieghem, Andrew T.L. Ong, Jiro Aoki, Gaston A. Rodriguez Granillo, Eugene P. McFadden, Arie Pieter Kappetein, Pim J. de Feyter, Pieter C. Smits, Evelyn Regar, Willem J. Van der Giessen, George Sianos, Peter de Jaegere, Ron T. Van Domburg, Patrick W. Serruys
Journal: Circulation (2005)

Background— The impact of drug-eluting stent (DES) implantation on the incidence of major adverse cardiovascular events in patients undergoing percutaneous intervention for left main (LM) coronary disease is largely unknown. Methods and Results— From April 2001 to December 2003, 181 patients underwent percutaneous coronary intervention for LM stenosis at our institution. The first cohort consisted of 86 patients (19 protected LM) treated with bare metal stents (pre-DES group); the second cohort comprised 95 patients (15 protected LM) treated exclusively with DES. The 2 cohorts were well balanced for all baseline characteristics. At a median follow-up of 503 days (range, 331 to 873 days), the cumulative incidence of major adverse cardiovascular events was lower in the DES cohort than in patients in the pre-DES group (24% versus 45%, respectively; hazard ratio [HR], 0.52 [95% CI, 0.31 to 0.88]; P =0.01). Total mortality did not differ between cohorts; however, there were significantly lower rates of both myocardial infarction (4% versus 12%, respectively; HR, 0.22 [95% CI, 0.07 to 0.65]; P =0.006) and target vessel revascularization (6% versus 23%, respectively; HR, 0.26 [95% CI, 0.10 to 0.65]; P =0.004) in the DES group. On multivariate analysis, use of DES, Parsonnet classification, troponin elevation at entry, distal LM location, and reference vessel diameter were independent predictors of major adverse cardiovascular events. Conclusions— When percutaneous coronary intervention is undertaken at LM lesions, routine DES implantation, which reduces the cumulative incidence of myocardial infarction and the need for target vessel revascularization compared with bare metal stents, should currently be the preferred strategy.
Effect of concomitant HIV infection on presentation and outcome of rotavirus gastroenteritis in Malawian children
Authors: Nigel A Cunliffe, Jailosi S Gondwe, Carl D Kirkwood, Stephen M Graham, Ndina M Nhlane, Benson DM Thindwa, Winifred Dove, Robin L Broadhead, Malcolm E Molyneux, C Anthony Hart
Journal: The Lancet (2001)
Association between Body-Mass Index and Risk of Death in More Than 1 Million Asians
Authors: Wei Zheng, Dale F. McLerran, Betsy Rolland, Xianglan Zhang, Manami Inoue, Keitaro Matsuo, Jiang He, Prakash Chandra Gupta, Kunnambath Ramadas, Shoichiro Tsugane, Fujiko Irie, Akiko Tamakoshi, Yu-Tang Gao, Renwei Wang, Xiao-Ou Shu, Ichiro Tsuji, Shinichi Kuriyama, Hideo Tanaka, Hiroshi Satoh, Chien-Jen Chen, Jian-Min Yuan, Keun-Young Yoo, Habibul Ahsan, Wen-Harn Pan, Dongfeng Gu, Mangesh Suryakant Pednekar, Catherine Sauvaget, Shizuka Sasazuki, Toshimi Sairenchi, Gong Yang, Yong-Bing Xiang, Masato Nagai, Takeshi Suzuki, Yoshikazu Nishino, San-Lin You, Woon-Puay Koh, Sue K. Park, Yu Chen, Chen-Yang Shen, Mark Thornquist, Ziding Feng, Daehee Kang, Paolo Boffetta, John D. Potter
Journal: New England Journal of Medicine (2011)

Most studies that have evaluated the association between the body-mass index (BMI) and the risks of death from any cause and from specific causes have been conducted in populations of European origin.We performed pooled analyses to evaluate the association between BMI and the risk of death among more than 1.1 million persons recruited in 19 cohorts in Asia. The analyses included approximately 120,700 deaths that occurred during a mean follow-up period of 9.2 years. Cox regression models were used to adjust for confounding factors.In the cohorts of East Asians, including Chinese, Japanese, and Koreans, the lowest risk of death was seen among persons with a BMI (the weight in kilograms divided by the square of the height in meters) in the range of 22.6 to 27.5. The risk was elevated among persons with BMI levels either higher or lower than that range--by a factor of up to 1.5 among those with a BMI of more than 35.0 and by a factor of 2.8 among those with a BMI of 15.0 or less. A similar U-shaped association was seen between BMI and the risks of death from cancer, from cardiovascular diseases, and from other causes. In the cohorts comprising Indians and Bangladeshis, the risks of death from any cause and from causes other than cancer or cardiovascular disease were increased among persons with a BMI of 20.0 or less, as compared with those with a BMI of 22.6 to 25.0, whereas there was no excess risk of either death from any cause or cause-specific death associated with a high BMI.Underweight was associated with a substantially increased risk of death in all Asian populations. The excess risk of death associated with a high BMI, however, was seen among East Asians but not among Indians and Bangladeshis.
Involvement of a disintegrin and a metalloproteinase 8 (ADAM8) in osteoclastogenesis and pathological bone destruction
Authors: M Ainola, T-F Li, J Mandelin, M Hukkanen, S J Choi, J Salo, Y T Konttinen
Journal: Annals of the Rheumatic Diseases (2008)

The eventual role of a disintegrin and a metalloproteinase 8 (ADAM8) in osteoclastogenesis was studied in erosive rheumatoid arthritis (RA) and in vitro.ADAM8 protein and mRNA expression was measured in RA pannus and synovitis and compared to osteoarthritic (OA) synovial membrane. Human monocytes were isolated and stimulated with proinflammatory cytokines and their ADAM8 expression and surface ADAM8 were measured. Human peripheral blood monocytes and RAW 264.7 mouse monocyte/macrophage cells were stimulated to osteclast like-cells, and their expression of ADAM8 and osteoclastic markers (calcitonin receptor, integrin beta 3, cathepsin K, TRAP) were analysed. Transfection and small interfering RNA (siRNA) were used to assess the role of ADAM8 in formation of polykaryons.Increased numbers of ADAM8 positive cells were shown particularly in the pannus-cartilage/bone junction close or adjoining to TRAP positive multinucleate cells under formation (60 (2)% in pannus, 47 (2)% in synovitis vs 10 (1)% in OA, p<0.001). Human pannus contained high ADAM8 mRNA copy numbers (23 (7) in pannus, 14 (4) in synovitis vs 1.7 (0.3) in OA, p<0.001). Functional studies in vitro disclosed ADAM8 mRNA and protein, which was first converted to a proteolytically active and then to fusion-active form. Gene transfection and siRNA experiments enhanced and inhibited, respectively, expression of osteoclast markers and maturation of multinuclear cells.ADAM8 may be involved in bone destruction in RA because it is upregulated in RA pannus adjacent to developing erosions and enhances maturation of osteoclast-like cells.
Human genomic regions with exceptionally high levels of population differentiation identified from 911 whole-genome sequences
Authors: Vincenza Colonna, Qasim Ayub, Yuan Chen, Luca Pagani, Pierre Luisi, Marc Pybus, Erik Garrison, Yali Xue, Chris Tyler-Smith
Journal: Genome biology (2014)

Population differentiation has proved to be effective for identifying loci under geographically localized positive selection, and has the potential to identify loci subject to balancing selection. We have previously investigated the pattern of genetic differentiation among human populations at 36.8 million genomic variants to identify sites in the genome showing high frequency differences. Here, we extend this dataset to include additional variants, survey sites with low levels of differentiation, and evaluate the extent to which highly differentiated sites are likely to result from selective or other processes. We demonstrate that while sites with low differentiation represent sampling effects rather than balancing selection, sites showing extremely high population differentiation are enriched for positive selection events and that one half may be the result of classic selective sweeps. Among these, we rediscover known examples, where we actually identify the established functional SNP, and discover novel examples including the genes ABCA12, CALD1 and ZNF804, which we speculate may be linked to adaptations in skin, calcium metabolism and defense, respectively. We identify known and many novel candidate regions for geographically restricted positive selection, and suggest several directions for further research.
Studies on the mechanisms of macrophage activation. I. Destruction of intracellular Leishmania enriettii in macrophages activated by cocultivation with stimulated lymphocytes.
Authors: J Mauel, Y Buchmüller, R Behin
Journal: The Journal of Experimental Medicine (1978)

When cultures of normal mouse peritoneal macrophages were infected with the intracellular protozoan parasite Leishmania enrietti, the micro-organism was found to survive intracellularly for several days, apparently without multiplication. However, exposure of infected macrophages to certain stimuli led to rapid parasite killing and digestion, providing a sensitive assay with which the mechanisms of macrophage activation can be studied. Microbicidal activity was induced by incubation of macrophages with syngeneic spleen lymphocytes, which were stimulated either by allogeneic cells in mixed lymphocyte culture (MLC) or by the plant lectin concanavalin A (Con A). Cocultivation with MLCs led to parasite killing within 48-72 h, whereas exposure of infected cells to Con A-stimulated lymphocytes resulted in substantial destruction of the micro-organism within less than 24 h, an effect which was dependent on the presence of thymus-derived lymphocytes and was inhibited by alpha methyl-mannoside. Incubation with Con A-stimulated lymphocytes also led to lysis of part of the macrophage monolayer. However, parasite killing did not result from decreased macrophage survival, as destruction of the micro-organism was highest under culture conditions which were the least detrimental to the phagocytes. Conversely, excess numbers of Con A-stimulated lymphocytes were less efficient at inducing macrophage activation and displayed marked toxicity to the macrophage monolayer. When spleen cells were stimulated by Con A at concentrations above 10 mug/ml, a decrease was noted in the capacity of macrophages to destroy the parasite, probably reflecting a toxicity of the lectin for lymphocytes resulting in impaired activating capacity.
Dual Inhibition of Class IA Phosphatidylinositol 3-Kinase and Mammalian Target of Rapamycin as a New Therapeutic Option for T-Cell Acute Lymphoblastic Leukemia
Authors: Francesca Chiarini, Federica Falà, Pier Luigi Tazzari, Francesca Ricci, Annalisa Astolfi, Andrea Pession, Pasqualepaolo Pagliaro, James A. McCubrey, Alberto M. Martelli
Journal: Cancer Research (2009)

Recent investigations have documented that constitutively activated phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling is a common feature of T-cell acute lymphoblastic leukemia (T-ALL), where it strongly influences growth and survival. These findings lend compelling weight for the application of PI3K/Akt/mTOR inhibitors in T-ALL. However, our knowledge of PI3K/Akt/mTOR signaling in T-ALL is limited and it is not clear whether it could be an effective target for innovative therapeutic strategies. Here, we have analyzed the therapeutic potential of the dual PI3K/mTOR inhibitor PI-103, a small synthetic molecule of the pyridofuropyrimidine class, on both T-ALL cell lines and patient samples, which displayed constitutive activation of PI3K/Akt/mTOR signaling. PI-103 inhibited the growth of T-ALL cells, including 170-kDa P-glycoprotein overexpressing cells. PI-103 cytotoxicity was independent of p53 gene status. PI-103 was more potent than inhibitors that are selective only for PI3K (Wortmannin, LY294002) or for mTOR (rapamycin). PI-103 induced G(0)-G(1) phase cell cycle arrest and apoptosis, which was characterized by activation of caspase-3 and caspase-9. PI-103 caused Akt dephosphorylation, accompanied by dephosphorylation of the Akt downstream target, glycogen synthase kinase-3beta. Also, mTOR downstream targets were dephosphorylated in response to PI-103, including p70S6 kinase, ribosomal S6 protein, and 4E-BP1. PI-103 strongly synergized with vincristine. These findings indicate that multitargeted therapy toward PI3K and mTOR alone or with existing drugs may serve as an efficient treatment toward T-ALL cells, which require up-regulation of PI3K/Akt/mTOR signaling for their survival and growth.
Bone marrow in vitro growth and cytogenetic studies in patients with fab-classified primary myelodysplastic syndromes
Authors: Birgitta Swolin, Stig Rödjer, Jan Westin
Journal: American Journal of Hematology (1990)

Abstract Thirty‐eight consecutive patients with a FAB‐classified primary myelodysplastic syndrome (MDS) were investigated for in vitro growth of colony‐forming units for granulocyte‐macrophage precursors (CFU‐GM) and cytogenetic analysis of bone marrow cells. Abnormal CFU‐GM growth was found in 30 patients (79%), and clonal chromosome abnormalities were found in 13 patients (34%). The eight patients who showed normal CFU‐GM growth were either cytogenetically normal (n = 5), or had a 5q‐ deletion (n = 3) as single or dominating karyotypic abnormality. Among the 30 patients with reduced or no colony growth, ten patients had a clonal chromosome abnormality. Leukemia developed in eight patients. None of them grew any CFU‐GM colonies, and three of them were cytogenetically abnormal at the time of diagnosis of MDS. Analysis of the bone marrow in vitro growth for CFU‐GM and the karyotype in patients with MDS emphasizes the close relationship between these disorders and manifest acute leukemia. Subgroups of MDS may be defined by a cytogenetic classification (e.g., the 5q‐ syndrome), and the CFU‐GM growth pattern can be of value for predicting leukemic transformation.
Late Effects of Hematopoietic Cell Transplantation Among 10-Year Adult Survivors Compared With Case-Matched Controls
Authors: Karen L. Syrjala, Shelby L. Langer, Janet R. Abrams, Barry E. Storer, Paul J. Martin
Journal: Journal of Clinical Oncology (2005)

To determine late effects of hematopoietic cell transplantation (HCT) on health problems and health-related quality of life for 10-year survivors.Four hundred five adults consented to the study before HCT. Medical records and standardized self-report measures were maintained prospectively. After 10 years, 137 survivors and nontransplant controls, case-matched on age, sex, and race, completed self-report of medical problems, symptoms, and health-related quality of life.Survivors and controls had similar rates of hospitalization and most diseases, but survivors reported an average of 3.5 medical problems versus 1.7 for controls (P < .001). Survivors reported more musculoskeletal stiffness, cramps, weakness and joint swelling (P < .001), cataract surgery (P < .001), hepatitis C (P = .004), sexual problems for men (P = .01) and women (P < .001), restrictions in social function (P = .002), memory and attention concerns (P = .003), urinary frequency or leaking (P = .006), use of psychotropic medication (P = .009), and denial of life and health insurance (P < .001). Survivors and controls did not differ in self-reported rates of osteoporosis, hypothyroidism, employment, marital satisfaction, divorce, or psychological health.Although indistinguishable in many respects, survivors had more medical needs than controls. Health problems were not focused on specific diseases or limited to survivors with readily identifiable risk factors. Musculoskeletal problems require both screening and research into etiologies and effective treatments. Osteoporosis and hypothyroidism may be underdiagnosed. Survivors require screening for sexual problems, urinary frequency, mood and need for antidepressants or benzodiazepines.
Collagen Triple Helix Repeat Containing 1, a Novel Secreted Protein in Injured and Diseased Arteries, Inhibits Collagen Expression and Promotes Cell Migration
Authors: Peter Pyagay, Mélanie Heroult, Qiaozeng Wang, Wolfgang Lehnert, John Belden, Lucy Liaw, Robert E. Friesel, Volkhard Lindner
Journal: Circulation Research (2004)

Collagen triple helix repeat containing 1 ( Cthrc1 ) was identified in a screen for differentially expressed sequences in balloon-injured versus normal arteries. Cthrc1 expression was not detectable in normal arteries. However, on injury it was transiently expressed by fibroblasts of the remodeling adventitia and by smooth muscle cells of the neointima. It was also found in the matrix of calcifying human atherosclerotic plaques. CTHRC1 is a secreted 28-kDa protein that is glycosylated and highly conserved from lower chordates to mammals. A short collagen motif with 12 Gly-X-Y repeats appears to be responsible for trimerization of the protein and this renders the molecule susceptible to cleavage by collagenase. Cthrc1 mRNA expression levels are increased in response to transforming growth factor-β and bone morphogenetic protein-4. Cell migration assays performed with CTHRC1-overexpressing fibroblasts and smooth muscle cells demonstrate that increased CTHRC1 levels are associated with enhanced migratory ability. Furthermore, CTHRC1 overexpression caused a dramatic reduction in collagen type I mRNA and protein levels. Our data indicate that the novel molecule CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration.
Effects of Cocaine Intoxication on the Threshold for Stun Gun Induction of Ventricular Fibrillation
Authors: Dhanunjaya Lakkireddy, Donald Wallick, Kay Ryschon, Mina K. Chung, Jagdish Butany, David Martin, Walid Saliba, William Kowalewski, Andrea Natale, Patrick J. Tchou
Journal: Journal of the American College of Cardiology (2006)
Preparticipation cardiovascular screening in young athletes
Authors: N M Panhuyzen-Goedkoop
Journal: British Journal of Sports Medicine (2009)

The sudden and unexpected death of an apparently healthy young athlete is relatively uncommon (0.5–2.1/100 000 athletes per year), but the catastrophic nature of these events mandates the medical community to adopt more widespread and extensive preparticipation cardiovascular screening (PPS).1 2

PPS in young athletes (<35 years old) is a systemic method to identify athletes at risk for life-threatening cardiovascular events.3 Excluding these athletes from competitive sports participation leads to a reduction in the incidence of exercise related sudden cardiac death (SCD).3 According to the Italian law all young competitive athletes (about 10% of the population) have been screened in a nationwide screening program in Italy for over 25 years. In the Veneto region in northern Italy, this resulted in a decrease of SCD among young athletes of 89% (from 3.6/100 000 per year in 1979 to 0.4/100 000 athletes per year in 2004).3 This reduction was predominantly attributed to identification of cardiomyopathy and electrical disease, and by excluding these athletes from competitive sports participation. The number of false positive test results was reported at 7%.3

The “Italian experience” is at the moment the only prospective population based study regarding PPS. This Italian protocol was adopted by the European Society of Cardiology (ESC) as the “common European protocol”, and by the International Olympic Committee (IOC), the international soccer association Federation Internationale de Football Association (FIFA) and the international federation for cyclists Union Cycliste Internationale (UCI) as …
<i>RAS</i>Mutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors
Authors: Fei Su, Amaya Viros, Carla Milagre, Kerstin Trunzer, Gideon Bollag, Olivia Spleiss, Jorge S. Reis-Filho, Xiangju Kong, Richard C. Koya, Keith T. Flaherty, Paul B. Chapman, Min Jung Kim, Robert Hayward, Matthew Martin, Hong Yang, Qiongqing Wang, Holly Hilton, Julie S. Hang, Johannes Noe, Maryou Lambros, Felipe Geyer, Nathalie Dhomen, Ion Niculescu-Duvaz, Alfonso Zambon, Dan Niculescu-Duvaz, Natasha Preece, Lídia Robert, Nicholas J. Otte, Stephen Mok, Damien Kee, Yan Ma, Chao Zhang, Gaston Habets, Elizabeth A. Burton, Bernice Wong, Hoa Nguyen, Mark Kockx, Luc Andries, Brian Lestini, Keith B. Nolop, Richard J. Lee, Andrew K. Joe, James L. Troy, Rene Gonzalez, Thomas E. Hutson, Igor Puzanov, Bartosz Chmielowski, Caroline J. Springer, Grant A. McArthur, Jeffrey A. Sosman, Roger S. Lo, Antoni Ribas, Richard Marais
Journal: New England Journal of Medicine (2012)

Cutaneous squamous-cell carcinomas and keratoacanthomas are common findings in patients treated with BRAF inhibitors.
Quality of Care for Patients With Type 2 Diabetes in Primary Care in Norway Is Improving
Authors: John Graham Cooper, Tor Claudi, Anne Karen Jenum, Geir Thue, Marie Fjelde Hausken, Wibeche Ingskog, Sverre Sandberg
Journal: Diabetes Care (2008)

To assess changes in the quality of care in Norway for patients with type 2 diabetes.Two cross-sectional surveys were examined that identified all patients (n = 1,470 in 1995 and n = 2,699 in 2005) with type 2 diabetes attending 33 general practices in 1995 and 2005.Between 1995 and 2005, there were significant improvements in the proportion of patients for whom important laboratory analyses, smoking habits, height, weight, and referral to eye examination were recorded. Mean A1C declined from 7.74 to 7.15%, systolic blood pressure from 150.0 to 140.4 mmHg, and cholesterol from 6.28 to 5.0 mmol/l (P < 0.001, age and sex adjusted). The 10-year risk of coronary heart disease for an average male patient declined from 42 to 29%.There have been substantial improvements in type 2 diabetes primary care in Norway that are potentially related to major improvements in health outcomes.
HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir
Authors: T.-W. Chun
Journal: Journal of Clinical Investigation (2005)

The persistence of latently infected, resting CD4+ T cells is considered to be a major obstacle in preventing the eradication of HIV-1 even in patients who have received effective antiviral therapy for an average duration of 5 years. Although previous studies have suggested that the latent HIV reservoir in the resting CD4+ T cell compartment is virologically quiescent in the absence of activating stimuli, evidence has been mounting to suggest that low levels of ongoing viral replication persist and in turn, prolong the overall half-life of HIV in patients receiving antiviral therapy. Here, we demonstrate the persistence of replication-competent virus in CD4+ T cells in a cohort of patients who had received uninterrupted antiviral therapy for up to 9.1 years that rendered them consistently aviremic throughout that time. Surprisingly, substantially higher levels of HIV proviral DNA were found in activated CD4+ T cells when compared with resting CD4+ T cells in the majority of patients we studied. Phylogenetic analyses revealed evidence for cross infection between the resting and activated CD4+ T cell compartments, suggesting that ongoing reactivation of latently infected, resting CD4+ T cells and spread of virus by activated CD4+ T cells may occur in these patients. Such events may allow continual replenishment of the CD4+ T cell reservoir and resetting of the half-life of the latently infected, resting CD4+ T cells despite prolonged periods of aviremia.