tbuckley/cabot-search huggingface dataset:
Streaks of White Hair in Popular Culture
Authors: Patricia M. Richey, Scott A. Norton
Journal: JAMA Dermatology (2015)

between erythematotelangiectatic rosacea and telangiectatic photoaging [publishedonlineMarch 23, 2015]. JAMADermatol. 2015. doi:10.1001 /jamadermatol.2014.4728. 14. Jinks JL, Fulker DW. Comparison of the biometrical genetical, MAVA, and classical approaches to the analysis of human behavior. Psychol Bull. 1970;73(5):311-349. 15. Diggle PJ, Liang K-Y, Zeger SL. Analysis of Longitudinal Data.New York, NY: Clarendon Press; 1994:253. 16. D’Agostino RB Jr. Propensity score methods for bias reduction in the comparison of a treatment to a non-randomized control group. Stat Med. 1998;17 (19):2265-2281. 17. Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:41-55. 18. Parsons LS. Performing a 1:N case-control match on propensity score. In: Proceedings of the 29th Annual SAS Users Group International Conference. Cary, NC: SAS Institute Inc; 2004:1-11. 19. Neale RE, Carriere P, MurphyMFG, Baade PD. Testicular cancer in twins: a meta-analysis. Br J Cancer. 2008;98(1):171-173. 20. Gosden RG, Treloar SA, Martin NG, et al. Prevalence of premature ovarian failure in monozygotic and dizygotic twins.Hum Reprod. 2007;22(2):610-615.
High-Resolution Definition of Vaccine-Elicited B Cell Responses Against the HIV Primary Receptor Binding Site
Authors: Christopher Sundling, Yuxing Li, Nick Huynh, Christian Poulsen, Richard Wilson, Sijy O’Dell, Yu Feng, John R. Mascola, Richard T. Wyatt, Gunilla B. Karlsson Hedestam
Journal: Science Translational Medicine (2012)

Vaccine-elicited mAbs bind the HIV-1 Env CD4bs differently from broadly neutralizing infection-induced mAbs.
New criteria to identify risk of progression in monoclonal gammopathy of uncertain significance and smoldering multiple myeloma based on multiparameter flow cytometry analysis of bone marrow plasma cells
Authors: Ernesto Pérez-Persona, María-Belén Vidriales, Gema Mateo, Ramón García-Sanz, Maria-Victoria Mateos, Alfonso García de Coca, Josefina Galende, Guillermo Martín-Nuñez, José M. Alonso, Natalia de las Heras, José M. Hernández, Alejandro Martín, Consuelo López-Berges, Alberto Orfao, Jesús F. San Miguel
Journal: Blood (2007)
p16INK4a reporter mice reveal age-promoting effects of environmental toxicants
Authors: Jessica A. Sorrentino, Janakiraman Krishnamurthy, Stephen Tilley, James G. Alb, Christin E. Burd, Norman E. Sharpless
Journal: Journal of Clinical Investigation (2013)

While murine-based systems to identify cancer-promoting agents (carcinogens) are established, models to identify compounds that promote aging (gerontogens) have not been described. For this purpose, we exploited the transcription of p16INK4a, which rises dynamically with aging and correlates with age-associated disease. Activation of p16INK4a was visualized in vivo using a murine strain that harbors a knockin of the luciferase gene into the Cdkn2a locus (p16LUC mice). We exposed p16LUC mice to candidate gerontogens, including arsenic, high-fat diet, UV light, and cigarette smoke and serially imaged animals to monitor senescence induction. We show that exposure to a high-fat diet did not accelerate p16INK4a expression, whereas arsenic modestly augmented, and cigarette smoke and UV light potently augmented, activation of p16INK4a-mediated senescence. This work provides a toxicological platform to study mammalian aging and suggests agents that directly damage DNA promote molecular aging.
N-glycan alterations are associated with drug resistance in human hepatocellular carcinoma
Authors: Takeaki Kudo, Hiroaki Nakagawa, Masato Takahashi, Jun Hamaguchi, Naoya Kamiyama, Hideki Yokoo, Kazuaki Nakanishi, Takahito Nakagawa, Toshiya Kamiyama, Kisaburo Deguchi, Shin-Ichiro Nishimura, Satoru Todo
Journal: Molecular Cancer (2007)

Abstract Background Correlations of disease phenotypes with glycosylation changes have been analysed intensively in the tumor biology field. Glycoforms potentially associated with carcinogenesis, tumor progression and cancer metastasis have been identified. In cancer therapy, drug resistance is a severe problem, reducing therapeutic effect of drugs and adding to patient suffering. Although multiple mechanisms likely underlie resistance of cancer cells to anticancer drugs, including overexpression of transporters, the relationship of glycans to drug resistance is not well understood. Results We established epirubicin (EPI) – and mitoxantrone (MIT) – resistant cell lines (HLE-EPI and HLE-MIT) from the human hepatocellular carcinoma cell line (HLE). HLE-EPI and HLE-MIT overexpressed transporters MDR1/ABCB1 and BCRP/ABCG2, respectively. Here we compared the glycomics of HLE-EPI and HLE-MIT cells with the parental HLE line. Core fucosylated triantennary oligosaccharides were increased in the two resistant lines. We investigated mRNA levels of glycosyltransferases synthesizing this oligosaccharide, namely, N-acetylglucosaminyltransferase (GnT)-IVa, GnT-IVb and α1,6-fucosyltransferase (α1,6-FucT), and found that α1,6-FucT was particularly overexpressed in HLE-MIT cells. In HLE-EPI cells, GnT-IVa expression was decreased, while GnT-IVb was increased. Both GnT-IVs were downregulated in HLE-MIT cells. HLE-MIT cells also showed decreases in fucosylated tetraantennary oligosaccharide, the product of GnT-V. GnT-V expression was decreased in both lines, but particularly so in HLE-MIT cells. Thus both N-glycan and glycosyltransferase expression was altered as cells acquired tolerance, suggesting novel mechanisms of drug resistance. Conclusion N-glycan and glycosyltransferase expression in HLE-EPI and HLE-MIT were analysed and presented that glycans altered according with acquired tolerance. These results suggested novel mechanisms of drug resistance.
Respiratory symptoms and FEV1 as predictors of hospitalization and medication in the following 12 years due to respiratory disease
Authors: J Vestbo, FV Rasmussen
Journal: European Respiratory Journal (1989)

The predictive value of cough, mucus hypersecretion, breathlessness, chronic bronchitis and forced expiratory volume in one second (FEV1) for hospitalization and medication were examined in a random population sample of 876 men, 46-69 yrs of age. All of the men were examined in 1974 with interview and lung function tests. Information on hospitalization in the period 1977-1986 was obtained from the Danish National Patient Register, and information on drug usage was obtained from 567 men in a questionnaire survey ultimo 1985. FEV1 was a strong predictor of both hospitalization and medication. Respiratory symptoms were good predictors of hospitalization due to either respiratory disease in general (odds ratios 2.56-3.29), or chronic obstructive pulmonary disease (COPD), (odds ratios 4.16-5.75). They contained predictive values in addition to that provided by FEV1. Respiratory symptoms were good predictors of medication for airway obstruction, relative risks 3.56-4.70, and/or airway disease in general, relative risks 2.67-4.69. After controlling for FEV1, cough was still significantly associated with treatment for airway disease in general and both cough, mucus hypersecretion and chronic bronchitis were significantly associated with treatment for airway obstruction. We conclude that apart from FEV1, respiratory symptoms are independent predictors of hospitalization and medication due to respiratory disease.
Is there a transient rise in sub-sarcolemmal Na and activation of Na/K pump current following activation of INa in ventricular myocardium?
Authors: B Silverman
Journal: Cardiovascular Research (2003)

Objective: The primary aim of this study was to investigate whether activation of Na influx via voltage-gated Na channels can elevate sub-sarcolemmal ('fuzzy-space') [Na] and transiently activate Na/K pump current (Ip). Methods and results: Initially, Na/K pump activity was characterised in whole-cell voltage-clamped single guinea-pig ventricular myocytes. Ip was activated by intracellular Na with a Km of 15.5 mM and a Hill coefficient of 1.7. Extracellular K activated Ip with a Km of 1.6 mM. In these experiments, a finite ouabain-sensitive Ip was measured when the pipette [Na] was zero. This suggests that there is an accumulation of Na in a sub-sarcolemmal space that is not in equilibrium with the bulk cytosol (which is assumed to be efficiently dialysed by the low-resistance patch-pipettes used). Such a sub-sarcolemmal Na gradient was observed in separate experiments in intact rabbit papillary muscles using electron probe X-ray microanalysis. In these studies, a fuzzy-space of limited Na diffusion was observed 100–200 nm below the sarcolemmal membrane. This sub-sarcolemmal Na gradient was similar whether muscles were frozen at peak-systole or end-diastole suggesting that the fuzzy-space Na does not change over the course of the contractile cycle. This was further investigated in isolated guinea pig myocytes where evidence for a transient activation of Ip was sought immediately after the activation of voltage-gated Na channels. A single clamp step from −80 to 0 mV activated Na influx but, in the 10–2000 ms immediately following the initial Na influx no evidence for a transient activation of Ip was observed. Similarly, no activation of Ip could be detected immediately following a train of 20 rapid (5-Hz) pulses designed to maximise Na influx. Conclusions: These studies provide evidence for the existence of a maintained sub-sarcolemmal elevation of [Na] in ventricular myocardium; however, this fuzzy-space [Na] did not change immediately after the activation of Na influx via voltage-gated Na channels or throughout the contractile cycle.
Evaluating the Role of Inducible Nitric Oxide Synthase Using a Novel and Selective Inducible Nitric Oxide Synthase Inhibitor in Septic Lung Injury Produced by Cecal Ligation and Puncture
Authors: IKU OKAMOTO, MASAYOSHI ABE, KAZUHIKO SHIBATA, NAOMI SHIMIZU, NORIYUKI SAKATA, TAKESHI KATSURAGI, KEIICHI TANAKA
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We studied the role of inducible nitric oxide synthase (iNOS) in septic lung injury using a novel and selective iNOS inhibitor (a fused piperidine derivative; ONO-1714) following a cecal ligation and puncture (CLP) procedure. All rats that received CLP died within 48 h after the intervention. The subcutaneous injection of ONO-1714 at 0.03 mg/kg every 12 h resulted in a significantly longer survival time than the saline control only when administration was started 12 h after the CLP procedure. The other administration schedules, which started immediately or 6 h after the intervention, did not show any improvement in the survival rates in comparison with the saline control. The administration of ONO-1714 at higher (0.1 mg/ kg) or lower (0.01 mg/kg) doses when given anytime after the intervention did not improve the survival rates. The NO(x) (NO(2)(-) + NO(3)(-)) levels in the plasma significantly increased 12 h after intervention in comparison with NO(x) at 0 h and thereafter further increased in parallel with the time elapsed. The CLP rats that were initially treated with ONO-1714 (0.03 mg/kg subcutaneously every 12 h) 12 h after intervention showed significantly reduced NO(x) levels in the plasma in comparison with the saline control. The NO synthase activity in lung homogenates increased from 6 to 24 h after the CLP and thereafter decreased to 42 h. The administration of ONO-1714 inhibited iNOS activity (under calcium-free conditions) in preference to total iNOS activity (under calcium-dependent conditions) in lung homogenates, which thus suggested that this compound selectively inhibited iNOS in lung tissue. The iNOS protein expression in the lung and liver homogenates showed a similar time course with alterations of NOS activity, namely a maximum level at 24 h after the intervention followed by decreasing levels to 42 h. On the other hand, other isozymes of NOS, eNOS, and nNOS in lung homogenates, were constantly expressed over the time course after the CLP. Since the iNOS mRNA expression in lung homogenates continued to elevate until 42 h, the decrease in iNOS activity and protein expression later than 24 h after the CLP was thus considered to be due to some posttranscriptional mechanism during the late phase of sepsis. In conclusion, intervention with a potent and selective iNOS inhibitor seemed to improve survival in CLP rats when used at the appropriate doses and time points. However, the self-limited mechanism of iNOS regulation in the lungs may also indicate that iNOS plays only a limited role in sepsis and septic shock.
Malaria burden and control in Bangladesh and prospects for elimination: an epidemiological and economic assessment
Authors: Ubydul Haque, Hans J Overgaard, Archie C A Clements, Douglas E Norris, Nazrul Islam, Jahirul Karim, Shyamal Roy, Waziul Haque, Moktadir Kabir, David L Smith, Gregory E Glass
Journal: The Lancet Global Health (2014)

Malaria is endemic in 13 of 64 districts in Bangladesh. About 14 million people are at risk. Some evidence suggests that the prevalence of malaria in Bangladesh has decreased since the the Global Fund to Fight AIDS, Tuberculosis and Malaria started to support the National Malaria Control Program (NMCP) in 2007. We did an epidemiological and economic assessment of malaria control in Bangladesh.We obtained annually reported, district-level aggregated malaria case data and information about disbursed funds from the NMCP. We used a Poisson regression model to examine the associations between total malaria, severe malaria, malaria-attributable mortality, and insecticide-treated net coverage. We identified and mapped malaria hotspots using the Getis-Ord Gi* statistic. We estimated the cost-effectiveness of the NMCP by estimating the cost per confirmed case, cost per treated case, and cost per person of insecticide-treated net coverage.During the study period (from Jan 1, 2008, to Dec 31, 2012) there were 285,731 confirmed malaria cases. Malaria decreased from 6.2 cases per 1000 population in 2008, to 2.1 cases per 1000 population in 2012. Prevalence of all malaria decreased by 65% (95% CI 65-66), severe malaria decreased by 79% (78-80), and malaria-associated mortality decreased by 91% (83-95). By 2012, there was one insecticide-treated net for every 2.6 individuals (SD 0.20). Districts with more than 0.5 insecticide-treated nets per person had a decrease in prevalence of 21% (95% CI 19-23) for all malaria, 25% (17-32) for severe malaria, and 76% (35-91) for malaria-associated mortality among all age groups. Malaria hotspots remained in the highly endemic districts in the Chittagong Hill Tracts. The cost per diagnosed case was US$0.39 (SD 0.02) and per treated case was $0.51 (0.27); $0.05 (0.04) was invested per person per year for health education and $0.68 (0.30) was spent per person per year for insecticide-treated net coverage.Malaria elimination is an achievable prospect in Bangladesh and failure to push for elimination nearly ensures a resurgence of disease. Consistent financing is needed to avoid resurgence and maintain elimination goals.None.
Antagonist Antibodies to PD-1 and B7-H1 (PD-L1) in the Treatment of Advanced Human Cancer—Response
Authors: Mario Sznol, Lieping Chen
Journal: Clinical Cancer Research (2013)

The immune suppressive molecule programmed death-1 (PD-1) is upregulated in activated T lymphocytes and inhibits T-cell function upon binding to its ligands B7-H1 (PD-L1, CD274) and B7-DC (PD-L2, CD273). Substantial experimental data from in vitro cell culture systems and animal models, and more recently from clinical trials, indicate that PD-1/PD-1-ligand interactions are a major mechanism of immune suppression within the tumor microenvironment. Initial clinical studies of antibodies directed against PD-1 and B7-H1 showed both an encouraging safety profile and remarkable antitumor activity in subsets of patients with metastatic disease, including malignancies--such as lung cancer--which were previously thought to be unresponsive to immunotherapy. Preliminary data have suggested a correlation between tumor membrane B7-H1 expression and clinical response to anti-PD-1 antibodies. Several key challenges remain to optimize development of PD-1/B7-H1 pathway blockade, including defining the biologic significance of all potential ligand-receptor interactions in the tumor microenvironment, developing more accurate predictive biomarkers of response, determining the breadth of activity in human malignancies, and developing rational combinations of therapy that address key mechanisms involved in positive and negative regulation of antitumor immune responses.
Rapid Immune Recovery and Graft-versus-Host Disease–like Engraftment Syndrome following Adoptive Transfer of Costimulated Autologous T Cells
Authors: Aaron P. Rapoport, Edward A. Stadtmauer, Nicole Aqui, Dan Vogl, Anne Chew, Hong-Bin Fang, Stephen Janofsky, Kelly Yager, Elizabeth Veloso, Zhaohui Zheng, Todd Milliron, Sandra Westphal, Julio Cotte, Hong Huynh, Andrea Cannon, Saul Yanovich, Gorgun Akpek, Ming Tan, Kristen Virts, Kathleen Ruehle, Carolynn Harris, Sunita Philip, Robert H. Vonderheide, Bruce L. Levine, Carl H. June
Journal: Clinical Cancer Research (2009)

Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-T at day +2 after transplant.In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2-restricted microltipeptide vaccine for HLA-A2(+) patients (arm A; n = 26).The mean number of T cells infused was 4.26 x 10(10) (range, 1.59-5.0). At day 14 after transplant, the median CD3, CD4, and CD8 counts were 4,198, 1,545, and 2,858 cells/microL, respectively. Interleukin (IL)-6 and IL-15 levels increased early after transplant and IL-15 levels correlated significantly to day 14 T-cell counts. Robust vaccine-specific B- and T-cell responses were generated. T-cell infusions were well tolerated with no effect on hematopoietic recovery. Eight patients (16%) developed a T-cell "engraftment syndrome" characterized by diarrhea and fever that was clinically and histopathologically indistinguishable from grade 1 to 3 acute graft-versus-host disease (GVHD) of the gastrointestinal tract (seven patients) and/or grade 1 to 2 cutaneous GVHD (four patients).Adoptive T-cell transfers achieve robust T-cell recovery early after transplant and induce moderate-to-severe autologous GVHD in a subset of patients.
Reduced Myocardial and Systemic <scp>l</scp> -Arginine Uptake in Heart Failure
Authors: David M. Kaye, Melinda M. Parnell, Belinda A. Ahlers
Journal: Circulation Research (2002)

Altered nitric oxide (NO) bioavailability has been ascribed an important role in the pathophysiology of congestive heart failure (CHF). In the peripheral vasculature, we recently demonstrated a depression of l -arginine transport in association with pharmacological evidence of reduced endothelial function. In contrast, increased myocardial NO generation has been proposed to account for a component of the reduced myocardial contractility in CHF, although this remains controversial. We determined the whole body clearance rate and cardiac fractional extraction of l -arginine during a steady-state intravenous infusion of [ 3 H] l -arginine (300 nCi/min) in 9 healthy control subjects and 7 patients with moderate to severe CHF. In patients with CHF, there was a 30% reduction in the transcardiac extraction of [ 3 H] l -arginine compared with controls ( P &lt;0.05), which was accompanied by a trend toward reduced [ 3 H] l -citrulline release ( P =0.06). In conjunction, the systemic clearance rate of [ 3 H] l -arginine was significantly lower in patients with CHF (778±148 versus 1278±144 mL/min, P &lt;0.05). In association with these biochemical indices, we observed a 38% reduction ( P &lt;0.05) in the mRNA expression of the cationic amino acid transporter CAT-1 in ventricular myocardial samples from patients with CHF compared with healthy unused donor myocardium, whereas myocardial NOS enzymatic activity and NOS protein were unchanged. These data indicate the presence of a significant reduction in the myocardial uptake of l -arginine in patients with CHF. Furthermore, this abnormality seems to be part of a systemic downregulation of l -arginine transport.
Plasma 25-Hydroxyvitamin D Concentration and Risk of Incident Type 2 Diabetes in Women
Authors: Anastassios G. Pittas, Qi Sun, Joann E. Manson, Bess Dawson-Hughes, Frank B. Hu
Journal: Diabetes Care (2010)

To determine the association between 25-hydroxyvitamin D (25-OHD) concentration and risk of incident type 2 diabetes.In a nested case-control study conducted among 608 women with newly diagnosed type 2 diabetes and 559 control subjects in the Nurses' Health Study, we measured the association between baseline plasma 25-OHD concentration and risk of incident diabetes.After adjusting for matching factors and diabetes risk factors, including BMI, higher levels of plasma 25-OHD were associated with a lower risk for type 2 diabetes. The odds ratio for incident type 2 diabetes in the top (median 25-OHD, 33.4 ng/ml) versus the bottom (median 25-OHD, 14.4 ng/ml) quartile was 0.52 (95% CI 0.33-0.83). The associations were consistent across subgroups of baseline BMI, age, and calcium intake.Plasma 25-OHD concentration was associated with lower risk of incident type 2 diabetes in women.
VERBAL HALLUCINATIONS AS AUTOMATIC SPEECH
Authors: LOUIS N. GOULD
Journal: American Journal of Psychiatry (1950)

The verbal hallucination can be explained on the basis of known physiologic and psychologic principles. It is primarily a disorder of speech and not one of perception. Hyperactivity of the neuromuscular mechanism of speech and reversal to a former habit of speech expression produce an autonomy which the patient is powerless to influence and which he fails to recognize as belonging to his ego. The characteristic effects of sound and of the human voice, the factors of attention, preoccupation, and egocentricity, the reactions to "alien" speech, and to influence by "others," the need to explain and counteract —all augment an already existent vocal hypertension and perpetuate speech autonomy. Certain characteristics of the verbal hallucination can be explained on the basis of other former habits of speech expression and immature behavior. Preliminary research indicates facile participation of the hallucinating patient's own speech mechanism during imagined speaking and hearing. Therapy should be based on reduction of focal and general tension and on restoration of the social function of speech along with education in social living.