tbuckley/cabot-search huggingface dataset:
A Population-based Study of Morbidity and Mortality in Mannose-binding Lectin Deficiency
Authors: Morten Dahl, Anne Tybjærg-Hansen, Peter Schnohr, Børge G. Nordestgaard
Journal: The Journal of Experimental Medicine (2004)

Reduced levels of wild-type mannose-binding lectin (MBL) may increase susceptibility for infection, other common diseases, and death. We investigated associations between MBL deficiency and risk of infection, other common diseases, and death during 24, 24, and 8 yr of follow-up, respectively. We genotyped 9,245 individuals from the adult Danish population for three MBL deficiency alleles, B, C, and D, as opposed to the normal noncarrier A allele. Hospitalization incidence per 10,000 person. yr was 644 in noncarriers compared with 631 in heterozygotes (log-rank: P = 0.39) and 658 in deficiency homozygotes (P = 0.53). Death incidence per 10,000 person. yr was 235 in noncarriers compared with 244 in heterozygotes (P = 0.44) and 274 in deficiency homozygotes (P = 0.12). After stratification by specific cause of hospitalization or death, only hospitalization from cardiovascular disorders was increased in deficiency homozygotes versus noncarriers (P = 0.02). When retested in two case control studies, this association could not be confirmed. Incidence of hospitalization or death from infections or other serious common disorders did not differ between deficiency homozygotes and noncarriers. In conclusion, in this large study in an ethnically homogeneous Caucasian population, there was no evidence for significant differences in infectious disease or mortality in MBL-deficient individuals versus controls. Our results suggest that MBL deficiency is not a major risk factor for morbidity or death in the adult Caucasian population.
Measuring Functional, Communicative, and Critical Health Literacy Among Diabetic Patients
Authors: Hirono Ishikawa, Takeaki Takeuchi, Eiji Yano
Journal: Diabetes Care (2008)

Health literacy (HL), the capacity of individuals to access, understand, and use health information to make informed and appropriate health-related decisions, has been recognized as an important concept in patient education and disease management. This study examined the psychometric properties of newly developed scales for measuring three different levels of HL (i.e., functional, communicative, and critical) in patients with diabetes.The reliability and validity of the three HL scales were evaluated in a sample of 138 outpatients with type 2 diabetes. In addition, sociodemographic and clinical characteristics, knowledge of diabetes, information-seeking behaviors, and self-efficacy were assessed for each patient through a self-report questionnaire and review of electronic medical records.Scale items were constructed to directly reflect the definition of HL. Internal consistency of functional, communicative, and critical HL scales was adequately high (alpha = 0.84, alpha = 0.77, and alpha = 0.65, respectively). Three interpretable factors were identified in exploratory factor analysis. Correlations between HL scales and other measures supported the construct validity of the scales. The three HL scales were only moderately correlated with each other, suggesting that each represents a different domain of HL abilities and skills.Our newly developed HL scales are reliable and valid measures of three types of HL in diabetic patients. Exploring a patient's HL levels may provide a better understanding of the patient's potential barriers to self-management of disease and health-promoting behaviors.
Application of Mucin Quantitative Competitive Reverse Transcription Polymerase Chain Reaction in Assisting the Diagnosis of Malignant Pleural Effusion
Authors: CHONG-JEN YU, JIN-YUH SHEW, YUANG-SHUANG LIAW, SOW-HSONG KUO, KWEN-TAY LUH, PAN-CHYR YANG
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Aberrant expression of mucin genes occurs frequently in advanced cancer. Using quantitative competitive reverse transcriptase/polymerase chain reaction (QC RT-PCR), the expression of three mucin genes—MUC1 (widely expressed in epithelial cells), MUC2 (mainly expressed in intestinal epithelial cells), and MUC5AC (mainly from airway and gastric epithelial cells)—was evaluated in 112 patients with pleural effusions (including 54 cytologically positive malignant pleural effusions, 35 benign exudative pleural fluids, and 23 cytologically negative pleural effusions from cancer patients). The expression ratios of MUC1 and MUC5AC, but not MUC2 gene, were significantly higher in malignant than benign pleural fluids (p < 0.000). The cutoff value, sensitivity, and specificity of MUC1 expression ratio were: 0.126, 64.6%, and 95.7%; and were 0.028, 72.3%, and 95.7%, respectively, for MUC5AC. In combined evaluation with both MUC1 and MUC5AC, the sensitivity was 86.1% and specificity was 91.5%. The positive and negative predictive values were 93.3%, and 82.7%, respectively. We considered mucin QC RT-PCR to be a useful tool in assisting the diagnosis of malignant pleural effusion.
Thalidomide in Small Cell Lung Cancer: Wrong Drug or Wrong Disease?
Authors: C. Ruegg, S. Peters
Journal: JNCI Journal of the National Cancer Institute (2009)

Keywords: Phase-Ii Trial ; Maintenance Therapy ; Tumor Angiogenesis ; Multiple-Myeloma ; Double-Blind ; Chemotherapy ; Growth Reference EPFL-ARTICLE-159544doi:10.1093/jnci/djp208View record in Web of Science Record created on 2010-11-30, modified on 2017-05-12
An Explanation for the Increasing Incidence of Testis Cancer: Decreasing Age at First Full-Term Pregnancy
Authors: Brian E. Henderson, Ronald K. Ross, Mimi C. Yu, Leslie Bernstein
Journal: JNCI Journal of the National Cancer Institute (1997)

122,721 alone had fewer vomiting episodes (mean, two versus seven) (P ‫ס‬ .007).Six (86%) of the seven patients who received one dose of CP-122,721 alone as prophylaxis reported no delayed emesis.Acute emesis and delayed emesis were similar among the CP-122,721 doses.No adverse effects of 721 occurred.This trial reports the first use of a substance-P antagonist to prevent cisplatin-induced emesis.The most dramatic finding was the prevention of delayed vomiting in 83% of the patients given a single prophylactic dose of CP-122,721.Only 17% of previously treated individuals had no delayed emesis in their prior course (P ‫ס‬ .006).This observation that NK 1 receptor blockade prevents delayed emesis suggests that substance P may, in part, mediate this reflex.In patients receiving CP-122,721 alone as prophylaxis for acute cisplatininduced emesis, vomiting was lessened compared with historical data (7), showing activity against acute emesis.For patients who had experienced acute emesis with a serotonin antagonist and dexamethasone in prior cycles, control during a subsequent cycle with CP-122,721 did not decline as expected (12).These data suggest that NK 1 antagonists may provide additive acute control.Further study of NK 1 receptor antagonists provides a singular opportunity to improve our understanding and control of emesis.
Phosphodiesterase regulation of nitric oxide signaling
Authors: D KASS, E TAKIMOTO, T NAGAYAMA, H CHAMPION
Journal: Cardiovascular Research (2007)

Nitric oxide regulation of the cardiovascular system involves both cGMP-dependent and independent mechanisms. The former directly interacts with the family of catabolic phosphodiesterases (PDEs) that control cGMP levels and thus distal effects such as protein kinase G stimulation. Growing evidence supports an important role of several PDEs, including PDE1, PDE2, and PDE5, in the regulation of cGMP in both vascular smooth muscle and cardiac myocytes. These PDEs have relatively little impact on resting function, but they can potently modulate acute contractile tone in cells stimulated by external agonists such as angiotensin or catecholamines. Regulation by PDEs is compartmentalized, with selective interactions occurring between a given source of cGMP and PDE hydrolysis. PDE1 and/or PDE5 are also reportedly up-regulated in chronic disease conditions such as atherosclerosis or cardiac pressure-load stress and heart failure as well as in response to long-term exposure to nitrates. Such up-regulation is thought to contribute to vascular and cardiac pathophysiology and to drug tolerance. Recent studies utilizing selective PDE5 inhibitors support significant cross-signaling with NO-cGMP synthetic pathways that may be particularly helpful in treating certain disease states.
The Role of States in Improving Price Transparency in Health Care
Authors: Anna D. Sinaiko, Alyna T. Chien, Meredith B. Rosenthal
Journal: JAMA Internal Medicine (2015)

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Neutrophil TLR4 expression is reduced in the airways of infants with severe bronchiolitis
Authors: C P Halfhide, S P Brearey, B F Flanagan, J A Hunt, D Howarth, J Cummerson, S Edwards, C A Hart, R L Smyth
Journal: Thorax (2009)

<h3>Background:</h3> In respiratory syncytial virus (RSV) bronchiolitis, neutrophils account for &gt;80% of cells recovered from the airways in bronchoalveolar lavage (BAL) fluid. This study investigated neutrophil activation and Toll-like receptor (TLR) expression in the blood and lungs of infants with severe RSV bronchiolitis. <h3>Methods:</h3> BAL fluid and (blood) samples were collected from 24 (16) preterm and 23 (15) term infants ventilated with RSV bronchiolitis, and 12 (8) control infants. Protein levels and mRNA expression of CD11b, myeloperoxidase (MPO) and TLRs 2, 4, 7, 8 and 9 were measured in neutrophils. <h3>Results:</h3> Blood neutrophils had more CD11b in preterm and term infants with RSV bronchiolitis than control infants (p&lt;0.025) but similar amounts of MPO. BAL fluid neutrophils from infants with RSV bronchiolitis had greater amounts of CD11b and MPO than blood neutrophils and BAL fluid neutrophils from controls (p&lt;0.01). Blood neutrophils from term infants with RSV bronchiolitis had less total TLR4 protein than preterm infants with RSV bronchiolitis (p = 0.005), and both had less than controls (p&lt;0.04). Total TLR4 for each group was greater in BAL fluid neutrophils than in blood neutrophils. Blood neutrophils from preterm infants with RSV bronchiolitis had greater TLR4 mRNA expression than term infants with RSV bronchiolitis (p = 0.005) who had similar expression to controls (p = 0.625). <h3>Conclusions:</h3> In infants with severe RSV bronchiolitis, neutrophil activation starts in the blood and progresses as they are recruited into the airways. Total neutrophil TLR4 remains low in both compartments. TLR4 mRNA expression is unimpaired. This suggests that neutrophil TLR4 expression is deficient in these infants, which may explain why they develop severe RSV bronchiolitis.
The peptide-based thrombin inhibitor CRC 220 is a new substrate of the basolateral rat liver organic anion-transporting polypeptide
Authors: U Eckhardt, J A Horz, E Petzinger, W Stüber, M Reers, G Dickneite, H Daniel, M Wagener, B Hagenbuch, B Stieger, P J Meier
Journal: Hepatology (1996)

The peptidomimetic thrombin inhibitor CRC 220, 4–methoxy–2,3,6–trimethylphenylsulfonyl–l–aspartyl–d–4–amidinop henylalanyl– piperidide, is taken up into isolated rat hepatocytes through active, carrier–mediated transport. This uptake is inhibited by bile acids. Functional expression in Xenopus laevis oocytes was performed to identify the transport system responsible for the hepatocellular CRC 220 uptake. Injection of poly(A)+RNA in X. laevis oocytes resulted in a two– to three–times higher uptake of CRC 220, compared with uninjected or water–injected control oocytes. Taurocholate (200 mumol/L) inhibited this uptake completely. No uptake of the peptidomimetic thrombin inhibitor was observed, when X. laevis oocytes were injected with complementary RNA (cRNA) encoding either the cloned rat liver Na+– dependent taurocholate transporter Ntcp, the renal oligopeptide carrier rhaPT or the intestinal oligopeptide transporter PepT1. However, after injection of cRNA of the cloned rat liver Na+–independent organic anion transporting polypeptide oatp, a specific and saturable CRC 220 uptake was observed (Michaelis–Menten constant 29.5 mumol/L). Cis–inhibition with known oatp–substrates, e.g., 20 mumol/L Bromsulphalein (BSP), 2007 mumol/L taurocholate and 2007 mumol/L cholate, occurred in oatp–expressing X. laevis oocytes, whereas substrates of the two peptide carriers as well as dipeptide– and single–amino acid constituents of the thrombin inhibitor itself lacked any significant inhibitory effects. These data show that the modified dipeptide CRC 220 is a highly selective substrate of the organic anion transporting polypeptide oatp in the basolateral plasma membrane of rat hepatocytes.
The Laminin 511/521–binding site on the Lutheran blood group glycoprotein is located at the flexible junction of Ig domains 2 and 3
Authors: Tosti J. Mankelow, Nicholas Burton, Fanney O. Stefansdottir, Frances A. Spring, Stephen F. Parsons, Jan S. Pedersen, Cristiano L. P. Oliveira, Donna Lammie, Timothy Wess, Narla Mohandas, Joel Anne Chasis, R. Leo Brady, David J. Anstee
Journal: Blood (2007)
Duration of gluten exposure in adult coeliac disease does not correlate with the risk for autoimmune disorders
Authors: C Sategna Guidetti
Journal: Gut (2001)

<h3>BACKGROUND AND AIMS</h3> Duration of gluten exposure seems to predispose adolescents with coeliac disease to autoimmune diseases. In a retrospective cohort study, we assessed the relationship between autoimmune disorders and actual gluten exposure in patients in whom coeliac disease was diagnosed in adult life (⩾16 years). <h3>METHODS</h3> We screened for the presence of autoimmunity in 605 controls (16–84 years) and 422 patients (16–84 years), all of whom had been on gluten withdrawal for at least one year (median follow up 9.5 years). A logistic regression analysis, setting the prevalence of autoimmunity as the dependent variable, was employed to control for independent covariates as predictors of the risk of autoimmunity. <h3>RESULTS</h3> The prevalence of autoimmunity was threefold higher (p&lt;0.00001) in patients than in controls. Mean duration of gluten exposure was 31.2 and 32.6 years for patients with or without autoimmunity. Logistic regression showed that increased age at diagnosis of coeliac disease was related to the prevalence of autoimmune disease while "actual gluten exposure" which takes into account diet compliance, follow up, and age at diagnosis of autoimmune disorders were not predictive for the risk of developing autoimmune diseases (odds ratio 0.82 per year). <h3>CONCLUSION</h3> The prevalence of autoimmune diseases in patients with a late coeliac disease diagnosis does not correlate with duration of gluten intake. Early exposure to gluten may modify the immunological response. Gluten withdrawal does not protect patients with a late diagnosis from autoimmune diseases.
Gap junctions support the sustained phase of hypoxic pulmonary vasoconstriction by facilitating calcium sensitization
Authors: Igor V. Kizub, Ievgen V. Strielkov, Yasin Shaifta, Silke Becker, Jesus Prieto-Lloret, Vladimir A. Snetkov, Anatoly I. Soloviev, Philip I. Aaronson, Jeremy P.T. Ward
Journal: Cardiovascular Research (2013)

Methods and resultsStudies were performed in rat isolated intrapulmonary arteries (IPAs) mounted on a myograph and in anaesthetized rats. Hypoxia induced a biphasic HPV response in IPAs preconstricted with prostaglandin F2α (PGF2α, 3 µM) or 20 mM K+. The GJ inhibitors 18β-glycyrrhetinic acid (18β-GA, 30 µM), heptanol (3.5 mM), or 2-aminoethoxydiphenyl borate (2-APB) (75 µM) had little effect on the transient Phase 1 of HPV, but abolished the sustained Phase 2 which is associated with Ca2+ sensitization. The voltage-dependent Ca2+ channel blocker diltiazem (10 µM) had no effect on HPV, and did not alter the inhibitory action of 18β-GA. Sustained HPV is enhanced by high glucose (15 mM) via potentiation of Ca2+ sensitization, in the presence of high glucose 18β-GA still abolished sustained HPV. Simultaneous measurement of tension and intracellular Ca2+ using Fura PE-3 demonstrated that whilst 18β-GA abolished tension development during sustained HPV, it did not affect the elevation of intracellular Ca2+. Consistent with this, 18β-GA abolished hypoxia-induced phosphorylation of the Rho kinase target MYPT-1. In anaesthetized rats hypoxia caused a biphasic increase in systolic right ventricular pressure. Treatment with oral 18β-GA (25 mg/kg) abolished the sustained component of the hypoxic pressor response.
Chemoprevention of Colon Cancer by Organoselenium Compounds and Impact of High- or Low-Fat Diets
Authors: B. S. Reddy, C. V. Rao, K. El-Bayoumy, P. Upadhyaya, A. Rivenson, L. Martin, B. Pittman
Journal: JNCI Journal of the National Cancer Institute (1997)

Observational and experimental studies have suggested that dietary supplementation with selenium can inhibit the development of colon cancer. However, many forms of selenium are toxic. Consequently, the development of efficacious compounds with low toxicity has been pursued.Two synthetic organoselenium compounds, p-methoxy-benzyl selenocyanate (p-methoxy-BSC) and 1,4-phenylenebis(methylene)selenocyanate (p-XSC), were tested for their ability to inhibit colon carcinogenesis in rats that were treated with the carcinogen azoxymethane and fed low- or high-fat diets.Groups of 5-week-old male F344 rats (42 animals/ group) were fed either a high-fat diet or a low-fat diet with or without added p-methoxy-BSC (10 or 20 parts per million [ppm]) or p-XSC (20 ppm). Two weeks later, 30 animals in each group received a subcutaneous injection of azoxymethane (15 mg/kg body weight); 1 week later, they received a second injection. The remaining 12 rats in each group received two injections of saline. Three days after the second injection of carcinogen or saline, animals being fed diets with p-methoxy-BSC or p-XSC were switched to corresponding organoselenium-free low- or high-fat diets for the remainder of the study to determine the effects of the selenium compounds on the initiation phase of colon carcinogenesis. At that time, groups of animals that had been maintained on organoselenium-free low- or high-fat diets were switched to diets containing p-methoxy-BSC or p-XSC until the end of the study to determine the effects of these compounds on the postinitiation phase of colon carcinogenesis. All animals were killed during the 38th week after azoxymethane or saline treatment, and histopathologic analysis of the colon tumors was performed. Colon tumor incidence and multiplicity were analyzed statistically.No obvious toxic effects were observed following dietary administration of 10 or 20 ppmp-methoxy-BSC or 20 ppm p-XSC. Administration of 20 ppm p-methoxy-BSC in a high-fat diet during the initiation and postinitiation phases of colon carcinogenesis significantly (statistically) reduced colon tumor incidence; 10 ppmp-methoxy-BSC in a high-fat diet significantly reduced colon tumor incidence but only when it was given during the postinitiation phase. Colon tumor incidence was also significantly reduced when 20 ppm p-XSC was given in a high-fat diet during the initiation phase of colon carcinogenesis. When 20 ppm p-XSC was administered in either a high-fat diet or a low-fat diet during the postinitiation phase, both colon tumor incidence and multiplicity were significantly reduced; the greatest reductions were in animals fed a low-fat diet.In this model system, p-methoxy-BSC and p-XSC are effective agents for the chemoprevention of colon cancer. The effects of p-XSC were enhanced in animals fed a low-fat diet.
P29 Do disturbances in cerebral oscillatory networks explain sleep and neuropsychiatric abnormalities in patients with cirrhosis
Authors: M Morgan, M Stubbs, H Dabrowski, C Jackson
Journal: Gut (2010)

Introduction  Patients with cirrhosis have significantly disturbed sleep–wake behaviour. However, the cause of these disturbances is uncertain and their relationship to hepatic encephalopathy (HE) is debated. Sleep is regulated by circadian and homeostatic processes; circadian abnormalities, while present in these patients, do not correlate with the observed disturbances in sleep–wake behaviour (Montagnese  et al , 2010). Homeostatic sleep mechanisms are difficult to access; the possibility that homeostatic control is disturbed in these patients has not been systematically studied. Sleep-spindles, which are a feature of the sleep electroencephalogram (EEG), are generated by thalamo-cortical oscillatory networks and are a surrogate marker for homeostatic sleep processes. The same oscillatory networks have been implicated in the pathogenesis of HE.  Aim  To examine homeostatic sleep mechanisms in patients with cirrhosis and to determine the relationship between sleep abnormalities and HE.  Method  39 patients with cirrhosis (24 men; 15 woman; mean (range) age 60 (37–85) years) were classified using clinical, psychometric and electrophysiological variables as neuropsychiatrically unimpaired (n=20), or as having minimal (n=6) or overt (n=13) HE. The reference population comprised 50 healthy individuals (26 men; 24 woman; age 55 (41–65) years. Sleep–wake behaviour was characterised using validated questionnaires. Sleep deprived EEGs were obtained in 14 patients (unimpaired (n=5), minimal (n=3) and overt (n=6) HE). The reference population comprised 26 healthy individuals (15 men; 11 woman; age 49 (39–59) years). The EEG was band-pass filtered (12.75–15.0 Hz) and the envelop of the sleep spindles obtained using the Hilbert transform. A threshold was identified which allowed the maximal rate of spindle occurrence to be defined. Variables were compared between patients and controls and in patients by degree of neuropsychiatric impairment.  Results  Patients with overt HE were significantly more likely to report night-time sleep disturbances and day-time napping than the control subject and unimpaired patients (p  The rate of sleep-spindle occurrence was significantly greater in the EEGs of patients with overt HE than in control subjects and unimpaired patients (59.2±3.8 vs 52.4±2.8, p  Conclusion  Sleep–wake disturbances were prevalent in the patients with cirrhosis and increased with the degree of neuropsychiatric impairment. Significant abnormalities were observed in the sleep EEGs in patients with overt HE. Thus, abnormalities in cerebral oscillatory networks may underlie both the sleep disturbances and the neuropsychiatric abnormalities observed in patient with cirrhosis