tbuckley/cabot-search huggingface dataset:
Egg Consumption and Risk of Type 2 Diabetes in Men and Women
Authors: Luc Djoussé, J. Michael Gaziano, Julie E. Buring, I-Min Lee
Journal: Diabetes Care (2008)

OBJECTIVE—Whereas limited and inconsistent findings have been reported on the relation between dietary cholesterol or egg consumption and fasting glucose, no previous study has examined the association between egg consumption and type 2 diabetes. This project sought to examine the relation between egg intake and the risk of type 2 diabetes in two large prospective cohorts. RESEARCH DESIGN AND METHODS—In this prospective study, we used data from two completed randomized trials: 20,703 men from the Physicians' Health Study I (1982–2007) and 36,295 women from the Women's Health Study (1992–2007). Egg consumption was ascertained using questionnaires, and we used the Cox proportional hazard model to estimate relative risks of type 2 diabetes. RESULTS—During mean follow-up of 20.0 years in men and 11.7 years in women, 1,921 men and 2,112 women developed type 2 diabetes. Compared with no egg consumption, multivariable adjusted hazard ratios for type 2 diabetes were 1.09 (95% CI 0.87–1.37), 1.09 (0.88–1.34), 1.18 (0.95–1.45), 1.46 (1.14–1.86), and 1.58 (1.25–2.01) for consumption of &amp;lt;1, 1, 2–4, 5–6, and ≥7 eggs/week, respectively, in men (P for trend &amp;lt;0.0001). Corresponding multivariable hazard ratios for women were 1.06 (0.92–1.22), 0.97 (0.83–1.12), 1.19 (1.03–1.38), 1.18 (0.88–1.58), and 1.77 (1.28–2.43), respectively (P for trend &amp;lt;0.0001). CONCLUSIONS—These data suggest that high levels of egg consumption (daily) are associated with an increased risk of type 2 diabetes in men and women. Confirmation of these findings in other populations is warranted.
De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy
Authors: Steffen Syrbe, Ulrike B S Hedrich, Erik Riesch, Tania Djémié, Stephan Müller, Rikke S Møller, Bridget Maher, Laura Hernandez-Hernandez, Matthis Synofzik, Hande S Caglayan, Mutluay Arslan, José M Serratosa, Michael Nothnagel, Patrick May, Roland Krause, Heidrun Löffler, Katja Detert, Thomas Dorn, Heinrich Vogt, Günter Krämer, Ludger Schöls, Primus E Mullis, Tarja Linnankivi, Anna-Elina Lehesjoki, Katalin Sterbova, Dana C Craiu, Dorota Hoffman-Zacharska, Christian M Korff, Yvonne G Weber, Maja Steinlin, Sabina Gallati, Astrid Bertsche, Matthias K Bernhard, Andreas Merkenschlager, Wieland Kiess, Michael Gonzalez, Stephan Züchner, Aarno Palotie, Arvid Suls, Peter De Jonghe, Ingo Helbig, Saskia Biskup, Markus Wolff, Snezana Maljevic, Rebecca Schüle, Sanjay M Sisodiya, Sarah Weckhuysen, Holger Lerche, Johannes R Lemke
Journal: Nature Genetics (2015)
Biomarkers of Response to Akt Inhibitor MK-2206 in Breast Cancer
Authors: Takafumi Sangai, Argun Akcakanat, Huiqin Chen, Emily Tarco, Yun Wu, Kim-Anh Do, Todd W. Miller, Carlos L. Arteaga, Gordon B. Mills, Ana Maria Gonzalez-Angulo, Funda Meric-Bernstam
Journal: Clinical Cancer Research (2012)

We tested the hypothesis that allosteric Akt inhibitor MK-2206 inhibits tumor growth, and that PTEN/PIK3CA mutations confer MK-2206 sensitivity.MK-2206 effects on cell signaling were assessed in vitro and in vivo. Its antitumor efficacy was assessed in vitro in a panel of cancer cell lines with differing PIK3CA and PTEN status. Its in vivo efficacy was tested as a single agent and in combination with paclitaxel.MK-2206 inhibited Akt signaling and cell-cycle progression, and increased apoptosis in a dose-dependent manner in breast cancer cell lines. Cell lines with PTEN or PIK3CA mutations were significantly more sensitive to MK-2206; however, several lines with PTEN/PIK3CA mutations were MK-2206 resistant. siRNA knockdown of PTEN in breast cancer cells increased Akt phosphorylation concordant with increased MK-2206 sensitivity. Stable transfection of PIK3CA E545K or H1047R mutant plasmids into normal-like MCF10A breast cells enhanced MK-2206 sensitivity. Cell lines that were less sensitive to MK-2206 had lower ratios of Akt1/Akt2 and had less growth inhibition with Akt siRNA knockdown. In PTEN-mutant ZR75-1 breast cancer xenografts, MK-2206 treatment inhibited Akt signaling, cell proliferation, and tumor growth. In vitro, MK-2206 showed a synergistic interaction with paclitaxel in MK-2206-sensitive cell lines, and this combination had significantly greater antitumor efficacy than either agent alone in vivo.MK-2206 has antitumor activity alone and in combination with chemotherapy. This activity may be greater in tumors with PTEN loss or PIK3CA mutation, providing a strategy for patient enrichment in clinical trials.
Composition of human colonic mucin. Selective alteration in inflammatory bowel disease.
Authors: D K Podolsky, K J Isselbacher
Journal: Journal of Clinical Investigation (1983)

Human colonic mucin has been isolated from mucosal scrapings of fresh surgical specimens of normal controls as well as patients with Crohn's colitis and ulcerative colitis. Following sonication and ultracentrifugation, mucin fractions were separated from other soluble colonic glycoproteins by Sepharose 4B chromatography. After nuclease digestion, cesium chloride gradient centrifugation of the excluded material yielded colonic mucin with an average buoyant density of 1.52 g/ml. Subsequent chromatography of the apparently homogeneous colonic mucin on DEAE-cellulose revealed the presence of at least six distinct mucin species (mucin I-VI). Each mucin species was found to have a distinctive hexose, hexosamine, sialic acid, and sulfate content as well as blood group substance activities. Mucin from five patients with Crohn's colitis was found to represent a mixture of at least six discrete species comparable to those isolated from normal colonic specimens. However, in mucin from eight patients with ulcerative colitis there was a marked and selective reduction of one component mucin subclass, designated species IV. Normal mucin and mucin from patients with Crohn's disease contained 48 +/- 17 and 42 +/- 12 mg of species IV/g, while mucin from patients with ulcerative colitis had 5 +/- 3 mg/g solubilized glycoprotein. The selective absence of species IV was found in preparations from both sigmoid (n = 7) and ascending (n = 4) colon and could not be accounted for by an overall decrease in total mucin content. The selective reduction of species IV was also found in mucin isolated from relatively noninflamed colonic mucosa of patients with ulcerative colitis. The carbohydrate composition and blood group activities of the remaining five mucin species were similar to their normal counterparts. Based on the results to date, there appears to be an underlying selective decrease of one colonic mucin subclass in ulcerative colitis.
Nuclear factor κB decoy oligodeoxynucleotides prevent endotoxin-induced fatal liver failure in a murine model
Authors: Ichiro Ogushi, Yuji Iimuro, Ekihiro Seki, Gakuhei Son, Tadamichi Hirano, Toshikazu Hada, Hiroko Tsutsui, Kenji Nakanishi, Ryuichi Morishita, Yasufumi Kaneda, Jiro Fujimoto
Journal: Hepatology (2003)

Endotoxin syndrome is a systemic inflammatory response mediated by inflammatory cytokines. Nuclear factor κB (NF–κB) is the dominant regulator of the production of these cytokines by inflammatory cells. The aim of this study was to assess the efficacy of in vivo transfer of synthetic double–stranded oligodeoxynucleotides (ODN) with high affinity against NF–κB (NF–κB/decoy/ODN) as a therapeutic strategy for treating endotoxin–induced fatal liver injury. Liver injury was induced by administration of lipopolysaccharide (LPS) to Propionibacterium acnes –primed BALB/C mice. NF–κB/decoy/ODN was transferred into the portal vein using a fusigenic liposome with hemagglutinating virus of Japan. NF–κB/decoy/ODN was preferentially transferred to Kupffer cells, and activation of NF–κB after the LPS challenge was suppressed, leading to decreased inflammatory cytokine production. As a result, the massive necrosis and hepatocyte apoptosis observed in the control mice was dramatically attenuated and the survival rate improved. In conclusion, NF–κB/decoy/ODN transfer in vivo effectively suppressed endotoxin–induced fatal liver injury in mice.
Asbestos inhalation induces reactive nitrogen species and nitrotyrosine formation in the lungs and pleura of the rat.
Authors: S Tanaka, N Choe, D R Hemenway, S Zhu, S Matalon, E Kagan
Journal: Journal of Clinical Investigation (1998)

To determine whether asbestos inhalation induces the formation of reactive nitrogen species, three groups of rats were exposed intermittently over 2 wk to either filtered room air (sham-exposed) or to chrysotile or crocidolite asbestos fibers. The rats were killed at 1 or 6 wk after exposure. At 1 wk, significantly greater numbers of alveolar and pleural macrophages from asbestos-exposed rats than from sham-exposed rats demonstrated inducible nitric oxide synthase protein immunoreactivity. Alveolar macrophages from asbestos-exposed rats also generated significantly greater nitrite formation than did macrophages from sham-exposed rats. Strong immunoreactivity for nitrotyrosine, a marker of peroxynitrite formation, was evident in lungs from chrysotile- and crocidolite-exposed rats at 1 and 6 wk. Staining was most evident at alveolar duct bifurcations and within bronchiolar epithelium, alveolar macrophages, and the visceral and parietal pleural mesothelium. Lungs from sham-exposed rats demonstrated minimal immunoreactivity for nitrotyrosine. Significantly greater quantities of nitrotyrosine were detected by ELISA in lung extracts from asbestos-exposed rats than from sham-exposed rats. These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative mechanism of asbestos-induced injury to that thought to be induced by Fenton reactions.
Predisposing factors to bacterial colonization in chronic obstructive pulmonary disease
Authors: R. Zalacain, V. Sobradillo, J. Amilibia, J. Barron, V. Achotegui, J.i. Pijoan, J.l. Llorente
Journal: European Respiratory Journal (1999)

The aim of this prospective observational study was to determine those factors influencing bacterial colonization in patients with stable chronic obstructive pulmonary disease (COPD). Eighty-eight outpatients with stable COPD and 20 patients with normal spirometry and chest radiography (controls) had a fibreoptic bronchoscopy performed with topical aerosol anaesthesia. Bacterial colonization was determined using the protected specimen brush (PSB) with a cut-off &gt; or = 10(3) colony-forming units (CFU x mL(-1)). The influence of age, degree of airflow obstruction, smoking habit, pack-yrs of smoking, and chest radiographic findings on bacterial colonization were assessed by univariate and multivariate analysis. Significant bacterial growth was found in 40% of patients and in none of the controls. Haemophilus influenzae, Streptococcus viridans, S. pneumoniae and Moraxella catarrhalis were the most frequent pathogens. After adjustment for other variables, severe airflow limitation (odds ratio (OR) 5.11, 95% confidence interval (CI) 1.45-17.9) and current smoking (OR 3.17, 95% CI 2.5-8) remained associated with positive bacterial cultures. When only potentially pathogenic micro-organisms were considered, significant bacterial growth was found in 30.7% of patients, with severe airflow obstruction (OR 9.28, 95% CI 2.19-39.3) being the only variable independently associated with positive bacterial cultures. Our results show that stable chronic obstructive pulmonary disease patients have a high prevalence of bacterial colonization of distal airways which is mainly related to the degree of airflow obstruction and cigarette smoking.
Brief Communication: Treatment of Enterococcus faecalis Endocarditis with Ampicillin plus Ceftriaxone
Authors: Joan Gavaldà
Journal: Annals of Internal Medicine (2007)

Background: High-level aminoglycoside resistance (HLAR) that precludes bactericidal synergism with penicillins or glycopeptides and nephrotoxicity related to aminoglycoside treatment are major problems in treating Enterococcus faecalis endocarditis. Objective: To evaluate the efficacy and safety of ampicillin plus ceftriaxone for treating endocarditis due to E. faecalis with and without HLAR. Design: Observational, open-label, nonrandomized, multicenter clinical trial. Setting: 13 centers in Spain. Patients: 21 patients with HLAR E. faecalis endocarditis and 22 patients with non-HLAR E. faecalis endocarditis. All were at risk for nephrotoxicity related to aminoglycoside use. Intervention: 6-week course of intravenous ampicillin, 2 g every 4 hours, plus intravenous ceftriaxone, 2 g every 12 hours. Measurements: Clinical and microbiological outcomes. Results: The clinical cure rate at 3 months was 67.4% (29 of 43 patients) among all episodes. During treatment, 28.6% of patients with HLAR E. faecalis endocarditis and 18.2% of patients with non-HLAR E. faecalis endocarditis died of infection-related causes. The rate of clinical and microbiological cure in patients who completed the protocol was 100% in the HLAR E. faecalis endocarditis group. No episodes of breakthrough bacteremia occurred, although there were 2 relapses in the non-HLAR E. faecalis endocarditis group. Treatment was withdrawn in 1 case because of fever and skin rash. Limitations: The study had a small sample and was observational. Conclusion: The combination of ampicillin and ceftriaxone is effective and safe for treating HLAR E. faecalis endocarditis and could be a reasonable alternative for patients with non-HLAR E. faecalis endocarditis who are at increased risk for nephrotoxicity.
No Price Too High?
Authors: Alan M. Garber
Journal: New England Journal of Medicine (1992)

Alglucerase offers the first real hope of reversing the glycolipid deposition responsible for the painful and sometimes life-threatening complications of Gaucher's disease. Because it is both uniquely promising and remarkably expensive, it poses stark dilemmas for patients, legislators, and physicians. Many patients treated with alglucerase risk the loss of their private health insurance coverage because they are likely to exceed its limits. Congress, which passed the Orphan Drug Act to encourage the development of treatments for uncommon conditions like Gaucher's disease, is now debating whether the act goes too far to protect the profits of pharmaceutical companies. Policy makers and . . .
Adjuvant Hormonal Therapy for Breast Cancer and Risk of Hormone Receptor–Specific Subtypes of Contralateral Breast Cancer
Authors: Christopher I. Li, Janet R. Daling, Peggy L. Porter, Mei-Tzu C. Tang, Kathleen E. Malone
Journal: Cancer Research (2009)

Compared with the breast cancer risk women in the general population have, breast cancer survivors have a substantially higher risk of developing a second primary contralateral breast cancer. Adjuvant hormonal therapy reduces this risk, but preliminary data indicate that it may also increase risk of hormone receptor-negative contralateral tumors. We conducted a population-based nested case-control study including 367 women diagnosed with both first primary estrogen receptor (ER)-positive invasive breast cancer and second primary contralateral breast cancer and 728 matched control women diagnosed only with a first breast cancer. Data on adjuvant hormonal therapy, other treatments, and breast cancer risk factors were ascertained through telephone interviews and medical record abstractions. Two-sided statistical tests using conditional logistic regression were conducted to quantify associations between adjuvant hormonal therapy and risk of hormone receptor-specific subtypes of contralateral breast cancer (n = 303 ER+ and n = 52 ER- cases). Compared with women not treated with hormonal therapy, users of adjuvant tamoxifen for >or=5 years had a reduced risk of ER+ contralateral breast cancer [odds ratio, 0.4; 95% confidence interval (CI), 0.3-0.7], but a 4.4-fold (95% CI, 1.03-19.0) increased risk of ER- contralateral breast cancer. Tamoxifen use for <5 years was not associated with ER- contralateral breast cancer risk. Although adjuvant hormonal therapy has clear benefits, risk of the relatively uncommon outcome of ER- contralateral breast cancer may now need to be tallied among its risks. This is of clinical concern given the poorer prognosis of ER- compared with ER+ tumors.
Fluoroscopically guided percutaneous gastrostomy in patients with cystic fibrosis
Authors: R F McLoughlin, G O'Connor, J Dowsett, M X Fitzgerald, R G Gibney
Journal: Thorax (1994)

The feasibility of fluoroscopically guided percutaneous gastrostomy in patients with cystic fibrosis is presented, highlighting differences between these and other patients undergoing the procedure.
Cardiac Myosin Light Chain-2
Authors: Wolfgang Rottbauer, Georgia Wessels, Tillman Dahme, Steffen Just, Nicole Trano, David Hassel, Charles Geoffrey Burns, Hugo A. Katus, Mark C. Fishman
Journal: Circulation Research (2006)

Although it is well known that mutations in the cardiac regulatory myosin light chain-2 ( mlc-2 ) gene cause hypertrophic cardiomyopathy, the precise in vivo structural and functional roles of MLC-2 in the heart are only poorly understood. We have isolated a mutation in zebrafish, tell tale heart ( tel m225 ), which selectively perturbs contractility of the embryonic heart. By positional cloning, we identified tel to encode the zebrafish mlc-2 gene. In contrast to mammals, zebrafish have only 1 cardiac-specific mlc-2 gene, which we find to be expressed in atrial and ventricular cardiomyocytes during early embryonic development, but also in the adult heart. Accordingly, loss of zMLC-2 function cannot be compensated for by upregulation of another mlc-2 gene. Surprisingly, ultrastructural analysis of tel cardiomyocytes reveals complete absence of organized thick myofilaments. Thus, our findings provide the first in vivo evidence that cardiac MLC-2 is required for thick-filament stabilization and contractility in the vertebrate heart.
Vasoactive intestinal peptide: cardiovascular effects
Authors: R Henning
Journal: Cardiovascular Research (2001)

Vasoactive intestinal peptide (VIP) is present in the peripheral and the central nervous systems where it functions as a nonadrenergic, noncholinergic neurotransmitter or neuromodulator. Significant concentrations of VIP are present in the gastrointestinal tract, heart, lungs, thyroid, kidney, urinary bladder, genital organs and the brain. On a molar basis, VIP is 50–100 times more potent than acetylcholine as a vasodilator. VIP release in the body is stimulated by high frequency (10–20 Hz) nerve stimulation and by cholinergic agonists, serotonin, dopaminergic agonists, prostaglandins (PGE, PGD), and nerve growth factor. The VIP peptide combines with its receptor and dose-dependently activates adenylyl cyclase. The vasodilatory effect of VIP in different vascular tissues or species also may be due to increases in nitric oxide, cyclic GMP, and other signaling agents. In the heart, VIP immunoreactive nerve fibers are present not only in the epicardial coronary arteries and veins, but also the sinoatrial node, atrium, interatrial septum, atrioventricular node, intracardiac ganglia, and ventricles (right ventricle ≫ left ventricle). In the coronary arterial walls, VIP may contribute to the regulation of normal coronary vasomotor tone. In research animals and in humans, VIP, administered into the coronary artery or intravenously, increases the epicardial coronary artery cross-sectional area, decreases coronary vascular resistance, and significantly increases coronary artery blood flow. High frequency parasympathetic (vagal) nerve stimulation also releases endogenous VIP in the coronary vessels and heart and significantly increases coronary artery blood flow. In addition, the release of VIP in the heart is increased during coronary artery occlusion and during reperfusion where VIP may promote local blood flow and may have a free-radical scavenging effect. VIP also has a primary positive inotropic effect on cardiac muscle that is enhanced by its ability to facilitate ventricular–vascular coupling by reducing mean arterial pressure by 10–15%. In concentrations of 10−8–10−5 mol, VIP augments developed isometric force and increases atrial and ventricular contractility. The presence of VIP-immunoreactive nerve fibers in and around the sinus and the atrioventricular nodes of mammals strongly suggests that this peptide can affect the heart rate. In this regard, endogenously released or exogenous VIP can significantly increase the heart rate and has a more potent effect on heart rate than does norepinephrine. The presence and significant cardiovascular effects of VIP in the heart suggests that this peptide is important in the regulation of coronary blood flow, cardiac contraction, and heart rate. Current investigations are defining the physiological role of VIP in the regulation of cardiovascular function.
PATIENT PERCEPTIONS OF THE QUALITY OF HEALTH SERVICES
Authors: Shoshanna Sofaer, Kirsten Firminger
Journal: Annual Review of Public Health (2005)

▪ Abstract As calls are made for a more patient-centered health care system, it becomes critical to define and measure patient perceptions of health care quality and to understand more fully what drives those perceptions. This chapter identifies conceptual and methodological issues that make this task difficult, including the confusion between patient perceptions and patient satisfaction and the difficulty of determining whether systematic variations in patient perceptions should be attributed to differences in expectations or actual experiences. We propose a conceptual model to help unravel these knotty issues; review qualitative studies that report directly from patients on how they define quality; provide an overview of how health plans, hospitals, physicians, and health care in general are currently viewed by patients; assess whether and how patient health status and demographic characteristics relate to perceptions of health care quality; and identify where further, or more appropriately designed, research is needed. Our aim is to find out what patients want, need and experience in health care, not what professionals (however well-motivated) believe they need or get. Through the Patient's Eyes ( 23 )
The Scientific Basis for Carcinogen Detection and Primary Cancer Prevention
Authors: I. B. Weinstein
Journal: CA A Cancer Journal for Clinicians (1982)

The primary prevention of specific human cancers must take into account the likelihood that most cancers result from a complex interaction between multiple environmental (exogenous) and host (endogenous) factors. In addition, the carcinogenic process often proceeds via multiple steps, including initiation, promotion, and progression. Therefore, assays are required that detect not only initiating carcinogens, but also tumor promoters, hormones, and various cofactors. The known biologic and biochemical properties of initiating carcinogens are reviewed and contrasted with those of tumor promoters. The implications of these differences with respect to the detection and assay of these agents are stressed.