tbuckley/cabot-search huggingface dataset:
A Selective Sweep across Species Boundaries in Drosophila
Authors: Cara L. Brand, Sarah B. Kingan, Longjun Wu, Daniel Garrigan
Journal: Molecular Biology and Evolution (2013)

Adaptive mutations that accumulate during species divergence are likely to contribute to reproductive incompatibilities and hinder gene flow; however, there may also be a class of mutations that are generally advantageous and can spread across species boundaries. In this study, we characterize a 15 kb region on chromosome 3R that has introgressed from the cosmopolitan generalist species Drosophila simulans into the island endemic D. sechellia, which is an ecological specialist. The introgressed haplotype is fixed in D. sechellia over almost the entirety of the resequenced region, whereas a core region of the introgressed haplotype occurs at high frequency in D. simulans. The observed patterns of nucleotide variation and linkage disequilibrium are consistent with a recently completed selective sweep in D. sechellia and an incomplete sweep in D. simulans. Independent estimates of both the time to the introgression and sweep events are all close to 10,000 years before the present. Interestingly, the most likely target of selection is a highly occupied transcription factor binding region. This work confirms that it is possible for mutations to be globally advantageous, despite their occurrence in divergent genomic and ecological backgrounds.
Ischemic Heart Disease after Renal Transplantation in Patients on Cyclosporine in Spain
Authors: Roberto Marcén, José María Morales, Manuel Arias, Gema Fernández-Juárez, Gema Fernández-Fresnedo, Amado Andrés, Emilio Rodrigo, Julio Pascual, Beatriz Domínguez, Joaquín Ortuño
Journal: Journal of the American Society of Nephrology (2006)

Ischemic heart disease (IHD), more common among transplant recipients than in the general population, accounts for approximately 50% of cardiovascular deaths. Despite its importance, only a few publications have addressed the prevalence of and risk factors for this complication. This was a retrospective cohort study in 2382 cadaver renal transplant recipients who were treated with cyclosporine as initial immunosuppression. Two groups were formed. The first group consisted of 163 patients with IHD, and the second group consisted of 326 patients without IHD. The prevalence of IHD was 6.8%, and the incidence was 15.7/1000 patient-years. Cardiac events presented during the first year in 62 (38%) patients. Multivariate analysis showed that the risk factors for IHD were age at transplant in years (relative risk [RR] 1.054; 95% confidence interval [CI] 1.033 to 1.075; P = 0.000), male gender (RR 1.940; 95% CI 1.221 to 3.081; P = 0.005), body weight at transplant in kg (RR 1.020; 95% CI 1.007 to 1.033; P = 0.002), pretransplantation cardiovascular disease (RR 2.150; 95% CI 1.733 to 3.359; P = 0.001), and a history of pretransplantation hypercholesterolemia (RR 2.032; 95% CI 1.378 to 2.998; P = 0.000). When only ischemic events that occurred 12 mo after transplantation were taken into consideration, the risk factors were age, male gender, body weight, smoking, and pretransplantation and posttransplantation hypercholesterolemia, whereas pretransplantation cardiovascular disease disappeared from the model. IHD affected nearly 7% of transplant recipients. Smoking, hypertension, and hypercholesterolemia constituted the treatable risk factors for IHD in this population. Emphasis should be placed on the need to stop smoking and to control hypertension and pre- and posttransplantation levels of serum cholesterol.
CD8+ T-Cell–Dependent Immunity Following Xenogeneic DNA Immunization against CD20 in a Tumor Challenge Model of B-Cell Lymphoma
Authors: Maria Lia Palomba, Wendy K. Roberts, Tao Dao, Gregory Manukian, Jose A. Guevara-Patiño, Jedd D. Wolchok, David A. Scheinberg, Alan N. Houghton
Journal: Clinical Cancer Research (2005)

The CD20 B-cell differentiation antigen is an attractive target for immunotherapy of B-cell lymphomas. In an experimental lymphoma model, BALB/c mice were immunized with mouse or human CD20 cDNA (mCD20 and hCD20, respectively) or their extracellular domains (minigenes). IFNgamma secretion by CD8+ T cells against CD20 was detected in mice vaccinated with hCD20 or human minigene, indicating that hCD20-primed CD8+ T cells recognize syngeneic CD20. Systemic challenge with syngeneic A20 cells, an aggressive lymphoma, resulted in long-term survival in a subset of immunized mice. Overall long-term survival was 14% in groups vaccinated with the human minigene versus 4% in control groups (P < 0.001). CD8+ T-cell depletion during the effector phase completely abrogated this effect. Antibodies against a recombinant mouse CD20 protein produced in insect cells were detected in mice immunized with hCD20 DNA and human and mouse minigene, but not in mice receiving mCD20 DNA. These results show that active immunization with xenogeneic DNA vaccines can induce CD8+ T cell-dependent immunity against CD20.
A Regulatory Mechanism for RSK2 NH2-Terminal Kinase Activity
Authors: Yong-Yeon Cho, Ke Yao, Angelo Pugliese, Margarita L. Malakhova, Ann M. Bode, Zigang Dong
Journal: Cancer Research (2009)

Our previous findings indicated that RSK2 plays a critical role in proliferation and cell transformation induced by tumor promoters, such as epidermal growth factor or 12-O-tetradecanoylphorbol-13-acetate, and that kaempferol, a natural compound found in edible plants, selectively inhibits RSK2 activity. However, the molecular mechanism for RSK2 activation is unclear. Herein, we provide evidence showing that NH(2)-terminal kinase domain (NTD) activation of RSK2 is required for the activation of the extracellular signal-regulated kinase-mediated COOH-terminal kinase domain (CTD). We also found that the NTD plays a key role in substrate phosphorylation and that kaempferol binds with the NTD but not the CTD in both the active and inactive forms. Homology modeling of the RSK2 NH(2)-terminal domain and small-molecule docking, validated by mutagenesis experiments, clearly showed that Val(82) and Lys(100) are critical amino acids for kaempferol binding and RSK2 activity. Furthermore, immunohistofluorescence and Western blot results indicated that the RSK2 protein level is markedly higher in cancer cell lines as well as cancer tissues compared with nonmalignant cell lines or normal tissues. In addition, kaempferol inhibited proliferation of malignant human cancer cell lines, including A431, SK-MEL-5 and SK-MEL-28, and HCT-116. These results indicate that targeting RSK2 with natural compounds, such as kaempferol, might be a good strategy for chemopreventive or chemotherapeutic application.
Spanish government accused of "manipulating" drugs bill figures
Authors: A. Garcia Rada
Journal: BMJ (2012)

Critics have questioned figures released by the Spanish government, which show that since the introduction of a controversial co-payment scheme introduced in June there has been a fall in the national drugs bill.1

Money spent on drugs was €702.86m (£555.88m; $882.04m) this July, 23% lower than the same month last year when it stood at €923.98m. The number of prescriptions has also fallen by 14%, the Spanish ministry of health, social services, and equality announced on 28 August. Both figures represent the largest falls since 1999, when monthly reports were introduced.

The new co-payment, one of the …
Tuberculosis Incidence in Prisons: A Systematic Review
Authors: Iacopo Baussano, Brian G. Williams, Paul Nunn, Marta Beggiato, Ugo Fedeli, Fabio Scano
Journal: PLoS Medicine (2010)

A systematic review by Iacopo Baussano and colleagues synthesizes published research to show that improved tuberculosis (TB) control in prisons could significantly reduce the burden of TB both inside and outside prisons.
Cytotoxic T lymphocytes recognize an HLA-A2 restricted epitope within the hepatitis B virus nucleocapsid antigen
Authors: A. Penna, F.V. Chisari, A. Bertoletti, G. Missale, T. Giuberti, S. Marchelli, L. Galati, F. Fiaccadori, C. Ferrari
Journal: Journal of Hepatology (1991)
Dopamine-Induced Alterations in Coronary Hemodynamics in Dogs
Authors: HAROLD L. BROOKS, PAUL D. STEIN, JAMES L. MATSON, JOHN W. HYLAND
Journal: Circulation Research (1969)

The effect of intravenous infusions of dopamine on left circumflex coronary blood flow and myocardial oxygen consumption in doses ranging from 5 to 100 µg/kg/min was studied in 17 open-chest dogs anesthetized with chloralose. Flow was measured with an electromagnetic flowmeter. Dopamine caused a progressive and linear increase of coronary flow that was proportional to increases in myocardial oxygen consumption up to a dose of 80 µg/kg/min; at this dose, the increase over control was 365% (28 to 129 ml/min). These changes accompanied marked increases in stroke volume, left ventricular dP/dt, and mean systolic ejection rate. Mean aortic pressure and heart rate changed little at doses below 10 µg/kg/min, but increased steadily with doses over the range of 15 to 40 µg/kg/min. Dopamine is a potent stimulator of coronary blood flow and myocardial contractility. The fact that the increased coronary flow was proportional to increases in myocardial oxygen consumption indicates that the induced coronary vasodilation is secondary to increased myocardial oxygen demands, rather than the result of primary coronary vasodilation.
Inhibition of p38α Mitogen-Activated Protein Kinase Prevents the Development of Osteolytic Bone Disease, Reduces Tumor Burden, and Increases Survival in Murine Models of Multiple Myeloma
Authors: Karin Vanderkerken, Satya Medicherla, Les Coulton, Hendrik De Raeve, Angelo Willems, Michelle Lawson, Ben Van Camp, Andrew A. Protter, Linda S. Higgins, Eline Menu, Peter I. Croucher
Journal: Cancer Research (2007)

The bone microenvironment plays a critical role in supporting the growth and survival of multiple myeloma as well as in the development of osteolytic bone disease. Signaling through p38alpha mitogen-activated protein kinase (MAPK) mediates synthesis of multiple myeloma cell growth factors, and its inhibition reduces proliferation in vitro. However, it is unclear whether targeting p38alpha MAPK prevents multiple myeloma growth and the development of bone disease in vivo. In this study, we determined whether SCIO-469, a selective p38alpha MAPK inhibitor, inhibits multiple myeloma growth and prevents bone disease in the 5T2MM and 5T33MM models. SCIO-469 decreased constitutive p38alpha MAPK phosphorylation of both 5T2MM and 5T33MM cells in vitro. This was associated with decreased DNA synthesis and an induction of apoptosis when the cells were cultured with bone marrow stromal cells. Treatment of C57Bl/KaLwRij mice bearing 5T33MM cells with SCIO-469 inhibited p38alpha MAPK phosphorylation and was associated with a significant decrease in serum paraprotein, an almost complete reduction in tumor cells in the bone marrow, a decrease in angiogenesis, and a significant increase in disease-free survival. Injection of 5T2MM murine myeloma cells into C57Bl/KaLwRij mice resulted in myeloma bone disease characterized by increased osteoclast occupation of the bone surface, reduced cancellous bone, and the development of osteolytic bone lesions. Treatment of 5T2MM-injected mice with SCIO-469 reduced this development of bone disease. Together, these data show that targeting p38alpha MAPK with SCIO-469 decreases myeloma burden in vivo, in addition to preventing the development of myeloma bone disease.
Validation of the 12-Gene Colon Cancer Recurrence Score as a Predictor of Recurrence Risk in Stage II and III Rectal Cancer Patients
Authors: Marlies S. Reimers, Peter J. K. Kuppen, Mark Lee, Margarita Lopatin, Haluk Tezcan, Hein Putter, Kim Clark-Langone, Gerrit Jan Liefers, Steve Shak, Cornelis J. H. van de Velde
Journal: JNCI Journal of the National Cancer Institute (2014)

The 12-gene Recurrence Score assay is a validated predictor of recurrence risk in stage II and III colon cancer patients. We conducted a prospectively designed study to validate this assay for prediction of recurrence risk in stage II and III rectal cancer patients from the Dutch Total Mesorectal Excision (TME) trial. RNA was extracted from fixed paraffin-embedded primary rectal tumor tissue from stage II and III patients randomized to TME surgery alone, without (neo)adjuvant treatment. Recurrence Score was assessed by quantitative real time–polymerase chain reaction using previously validated colon cancer genes and algorithm. Data were analysed by Cox proportional hazards regression, adjusting for stage and resection margin status. All statistical tests were two-sided. Recurrence Score predicted risk of recurrence (hazard ratio [HR] = 1.57, 95% confidence interval [CI] = 1.11 to 2.21, P = .01), risk of distant recurrence (HR = 1.50, 95% CI = 1.04 to 2.17, P = .03), and rectal cancer-specific survival (HR = 1.64, 95% CI = 1.15 to 2.34, P = .007). The effect of Recurrence Score was most prominent in stage II patients and attenuated with more advanced stage (Pinteraction ≤ .007 for each endpoint). In stage II, five-year cumulative incidence of recurrence ranged from 11.1% in the predefined low Recurrence Score group (48.5% of patients) to 43.3% in the high Recurrence Score group (23.1% of patients). The 12-gene Recurrence Score is a predictor of recurrence risk and cancer-specific survival in rectal cancer patients treated with surgery alone, suggesting a similar underlying biology in colon and rectal cancers.
Harnessing Poverty Alleviation to Reduce the Stigma of HIV in Sub-Saharan Africa
Authors: Alexander C. Tsai, David R. Bangsberg, Sheri D. Weiser
Journal: PLoS Medicine (2013)

N Poverty is an important driver of HIV stigma.N HIV-related morbidity undermines HIV-infected persons' ability to maintain their full economic contributions to family and community life.N Stigmatization and exclusion from local solidarity networks erode food and livelihood security, which undermine adherence to HIV treatment, further perpetuating this cycle.N HIV treatment can improve the economic, mental, and social health of HIV- infected persons, but it may not be sufficient to reduce the stigma of HIV.N Livelihood interventions can reduce the stigma of HIV by directly targeting poverty.
MOLECULAR GROWTH REQUIREMENTS OF SINGLE MAMMALIAN CELLS
Authors: Harold W. Fisher, Theodore T. Puck, Gordon Sato
Journal: The Journal of Experimental Medicine (1959)

Two purified serum protein fractions, fetuin and serum albumin, will replace whole or dialyzed serum in supporting the growth of single S3 HeLa cells in an otherwise chemically defined nutrient solution. In the serum-free medium, single S3 cells will form macroscopic colonies with essentially 100 per cent efficiency. The generation time of S3 cells in the serum-free medium is approximately 50 per cent greater than that observed in an optimal, serum-containing medium. All components of the serum-free medium are available commercially, except fetuin, which can easily be prepared in substantial quantities. The problem of the purity of the protein preparations and of their possible roles in promoting cell growth is discussed.
Turmeric and Green Tea: A Recipe for the Treatment of B-Chronic Lymphocytic Leukemia
Authors: Laura S. Angelo, Razelle Kurzrock
Journal: Clinical Cancer Research (2009)

Abstract Two naturally occurring compounds, curcumin, the active ingredient in the spice turmeric, and the green tea extract epigallocatechin-3-gallate, have marked effects on the apoptotic machinery in chronic lymphocytic leukemia. These results provide a preclinical foundation for future clinical use of these compounds in this disease.
Perinatal Changes in Myocardial Metabolism in Lambs
Authors: Beatrijs Bartelds, Hennie Knoester, Gioia B. Smid, Janny Takens, G. Henk Visser, Luit Penninga, Feike R. van der Leij, Gertie C. M. Beaufort-Krol, Willem G. Zijlstra, Hugo S. A. Heymans, Jaap R. G. Kuipers
Journal: Circulation (2000)

Lactate accounts for a third of myocardial oxygen consumption before and in the first 2 weeks after birth. It is unknown how the remainder of myocardial oxygen is consumed. Glucose is thought to be important before birth, whereas long-chain fatty acids (LC-FA) are the prime substrate for the adult. However, the ability of the myocardium of the newborn to use LC-FA has been doubted.We measured the myocardial metabolism of glucose and LC-FA with [U-(13)C]glucose and [1-(13)C]palmitate in chronically instrumented fetal and newborn lambs. In fetal lambs, myocardial oxidation of glucose was high and that of LC-FA was low. Glucose and LC-FA accounted for 48+/-4% and 2+/-2% of myocardial oxygen consumption, respectively. In newborn lambs, oxidation of glucose decreased, whereas oxidation of LC-FA increased. Glucose and LC-FA accounted for 12+/-3% and 83+/-19% of myocardial oxygen consumption. To test whether near-term fetal lambs could use LC-FA, we increased the supply of LC-FA with a fat infusion. In fetal lambs during fat infusion, the oxidation of LC-FA increased 15-fold. Although the oxidation of LC-FA was still lower than in newborn lambs, the contribution to myocardial oxygen consumption (70+/-13%) was the same as in newborn lambs.These data show that glucose and lactate account for the majority of myocardial oxygen consumption in fetal lambs, whereas in newborn lambs, LC-FA and lactate account for the majority of myocardial oxygen consumption. Moreover, we showed that the fetal myocardium can use LC-FA as an energy substrate.
Genetically engineered endothelial cells remain adherent and viable after stent deployment and exposure to flow in vitro.
Authors: M Y Flugelman, R Virmani, M B Leon, R L Bowman, D A Dichek
Journal: Circulation Research (1992)

Intravascular stents, currently in experimental human use for recurrent arterial stenosis, are plagued by subacute thrombosis. As a therapeutic approach to stent-related thrombosis, we and others have suggested coating stents with endothelial cells before implantation. In a previous study we demonstrated the feasibility of coating stents with endothelial cells that were genetically modified to secrete large amounts of human tissue plasminogen activator. In the present study we attempted both to develop a clinically applicable protocol for stent seeding and to test whether seeded cells would remain adherent to stents after exposure to pulsatile flow. Endothelial cells were harvested from the saphenous veins of sheep with survival of the donor animals. Harvested cells were transduced with a retroviral vector containing a marker gene and seeded onto catheter-mounted stents under sterile conditions. Scanning electron microscopy revealed complete coverage of the stent surfaces by seeded cells. Stents were expanded and exposed to pulsatile flow in vitro. Substantial cell retention was observed on the lateral stent surfaces by light microscopy and scanning electron microscopy; fewer cells were seen on the luminal and abluminal surfaces. Removal of seeded cells from flow-exposed stents by trypsin digestion resulted in the recovery of approximately 70% of the seeded cells. These cells were viable and healthy as judged by their ability to proliferate to confluence with the same kinetics as control (non-flow-exposed) cells. Autologous genetically modified endothelial cells can be seeded onto catheter-mounted stents in a sterile manner, and stent deployment under flow conditions results in substantial retention of viable cells.
Hormone Replacement Therapy Is Associated with Higher FEV<sub>1</sub> in Elderly Women
Authors: CATHERINE L. CARLSON, MARY CUSHMAN, PAUL L. ENRIGHT, JANE A. CAULEY, ANNE B. NEWMAN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Estrogen and progesterone use have been associated with improved pulmonary function in premenopausal women. However, little research has examined the relationship between hormone replacement therapy (HRT) and pulmonary function in postmenopausal women. We examined the relationship of HRT with spirometry in 2,353 women aged 65 yr and older participating in the Cardiovascular Health Study in 1993/1994. Current use of HRT was hypothesized to be associated with higher FEV1, higher FVC, and less pulmonary obstruction (FEV1/FVC < 65%). FEV1 was higher among current HRT users compared to noncurrent users in the following groups: overall (1.82 L versus 1.66 L, p < 0.0001), among women without asthma (1.85 L versus 1.69 L, p < 0.0001), among former smokers (1.76 L versus 1.60 L, p = 0.013), and among never smokers (1.90 L versus 1.72 L, p < 0.0001). Overall, HRT use was associated with a lower prevalence of pulmonary obstruction (OR 0.75 [95% CI 0.55, 0.99]). After controlling for potential confounders, HRT use was significantly associated with higher FEV(1) (p = 0.031) and with a lower prevalence of obstruction (OR 0.67 [95% CI 0.48, 0.95]). We conclude that postmenopausal women who use HRT have higher levels of FEV1 and less obstruction, which could not be explained by their lower rates of smoking and other health factors associated with HRT use.
Enhanced jejunal production of antibodies to Klebsiella and other Enterobacteria in patients with ankylosing spondylitis and rheumatoid arthritis
Authors: O. Maki-Ikola, R. Hallgren, L. Kanerud, N. Feltelius, L. Knutsson, K. Granfors
Journal: Annals of the Rheumatic Diseases (1997)

To measure gut immunity directly in jejunal fluid in patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA).Antibodies against three different Enterobacterias were measured in jejunal perfusion fluids (collected by a double balloon perfusion device) of 19 patients with AS, 14 patients with RA, and 22 healthy controls using enzyme linked immunosorbent assay.The AS patients had significantly increased jejunal fluid concentrations of IgM, IgG, and IgA class antibodies against Klebsiella pneumoniae, and IgM and IgA class antibodies against Escherichia coli and Proteus mirabilis compared with healthy controls. When compared with the patients with RA, the AS patients had higher concentrations of IgA and IgG class antibodies only against K pneumoniae. The RA patients had higher IgM class antibody concentrations against all three studied Enterobacterias, when compared with the healthy controls, suggesting an enhanced mucosal immune response in these patients. A three month treatment with sulphasalazine did not decrease enterobacterial antibody concentrations in the 10 patients with AS.There is strong direct evidence for an abnormal mucosal humoral immune response particularly to K pneumoniae in patients with AS.
Electrical Excitability of Atrioventricular Nodal Cells
Authors: JOHN MERIDETH, CARLOS MENDEZ, WILLIAM J. MUELLER, GORDON K. MOE
Journal: Circulation Research (1968)

The electrical threshold of A-V nodal cells of isolated rabbit heart preparations was estimated by techniques which permitted stimulation and recording through the same micropipette. Cells within the node were significantly less excitable than adjacent atrial and ventricular tissues; thresholds exceeded 5 x 10 -6 amp in some instances. Recovery of excitability was delayed well beyond repolarization; in cells of the midnodal region, "diastolic" threshold was not attained until 0.2 to 0.5 seconds after restoration of resting membrane potential. A cumulative effect of frequency upon excitability (fatigue) was demonstrated. At high driving rates, the lag in recovery was further delayed, and the late diastolic threshold was increased. Responses to single-cell stimulation indicate that summation may be an important feature of propagation within the node.
The Epidemiology of Tuberculosis in San Francisco -- A Population-Based Study Using Conventional and Molecular Methods
Authors: Peter M. Small, Philip C. Hopewell, Samir P. Singh, Antonio Paz, Julie Parsonnet, Delaney C. Ruston, Gisela F. Schecter, Charles L. Daley, Gary K. Schoolnik
Journal: New England Journal of Medicine (1994)

The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted.