tbuckley/cabot-search huggingface dataset:
Association of Hippocampal Atrophy With Cerebrospinal Fluid Antibodies Against the NR2 Subtype of the <i>N</i>‐Methyl‐<scp>D</scp>‐Aspartate Receptor in Patients With Systemic Lupus Erythematosus and Patients With Primary Sjögren's Syndrome
Authors: Maria B. Lauvsnes, Mona K. Beyer, Jan Terje Kvaløy, Ole J. Greve, Simone Appenzeller, Ingeborg Kvivik, Erna Harboe, Anne B. Tjensvoll, Lasse G. Gøransson, Roald Omdal
Journal: Arthritis & Rheumatology (2014)

Cognitive dysfunction is common in both systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (SS). Antibodies against the NR2 subtype of the N-methyl-D-aspartate receptor (anti-NR2 antibodies) cause hippocampal atrophy and cognitive impairment in mice and have been associated with memory impairment in both patients with SLE and patients with primary SS. In addition, a reduced volume of hippocampal gray matter has been demonstrated in both SLE and primary SS. This study was undertaken to investigate whether there is a connection between the presence of anti-NR2 antibodies and hippocampal atrophy in human diseases.Fifty patients with SLE and 50 patients with primary SS underwent clinical examination and cerebral magnetic resonance imaging. Anti-NR2 antibodies in cerebrospinal fluid (CSF) were measured, and hippocampal gray matter volumes were compared between patients who were positive for and those who were negative for anti-NR2 antibodies.Patients with anti-NR2 antibodies in CSF had less hippocampal gray matter than patients without these antibodies. No other differences regarding gray matter volumes in other parts of the brain were identified.The present findings indicate that anti-NR2 antibodies in patients with SLE and primary SS cause neuronal death manifested as reduced hippocampal gray matter, as has been previously demonstrated in mice with autoimmune disease.
Mutational analysis in familial and sporadic patients with white sponge naevus
Authors: X. Liu, Q. Li, Y. Gao, S. Song, H. Hua
Journal: British Journal of Dermatology (2011)

Funding sources: This work was supported by the National Key Health Research Project Foundation of China during the 11th Five‐Year Plan Period (2006BAI05A07). Conflicts of interest: none declared. Madam, We describe eight unrelated Chinese subjects with asymptomatic, white, soft, corrugated or shaggy plaques in the oral mucosa (Fig. 1a,b). After informed consent, biopsies were performed in all cases. Histologically, the affected lesions showed different degrees of epithelial oedema or vacuolization extending from the parabasal region to the near surface, especially in both the shallow spinous and the keratinized layers, dispersed keratohyalin granules in the shallow spinous layer (Fig. 1c,d), and, most importantly, conspicuous perinuclear eosinophilic condensation of the cytoplasm of prickle cells (Fig. 1e,f). Based on the clinical and histological features, all cases were identified as white sponge naevus (WSN; OMIM 193900). Three of the eight probands, whose families were affected, were classified into group A (subjects A1–3); the remaining five were sporadic cases and were classified into group B (subjects B1–5). The extraoral mucosa, including nasal, laryngeal, oesophageal, anal and vaginal mucosa, was inspected and no abnormality was found in any of the patients.
Effect of oxygen and acetazolamide on nocturnal cardiac conduction, repolarization and arrhythmias in pre-capillary pulmonary hypertension and sleep-disturbed breathing
Authors: Deborah Schumacher, Séverine Müller-Mottet, Elisabeth Hasler, Konrad E. Bloch, Silvia Ulrich
Journal: European Respiratory Journal (2014)

Background  :  Sleep-disturbed breathing (SDB) is common in patients with pre-capillary pulmonary hypertension (PH). Nocturnal oxygen therapy (NOT) and acetazolamide improve SDB and NOT improves exercise capacity. We investigated the effect of NOT and acetazolamide on nocturnal cardiac conduction, repolarization and arrhythmias in PH-patients with SDB.   Methods: In a randomized, placebo-controlled, double-blind, cross-over trial 23 patients with arterial (n=16) or thromboembolic PH (n=7) and SDB defined as a mean nocturnal oxygen saturation (SpO 2 )l90% or dips(g3%)g10/h were studied. Participants received NOT (3l/min), acetazolamide (2x250mg), and sham-NOT/placebo each during one week separated by one-week washout. Electrocardiography was recorded during overnight polysomnography at the end of each treatment period. Repolarization indices were averaged over three cardiac cycles at late evening and early morning and nocturnal arrhythmias were counted.   Results:  NOT was associated with a lower overnight (68±10 vs. 72±9bpm, p=0.010) and early morning heart rate compared with placebo. At late evening, the PQ c  was increased under acetazolamide compared with placebo (mean difference 10ms, 95%CI 0 to 20ms, p=0.042). In the morning under NOT, the QT c  was decreased compared with placebo (mean difference -25ms, 95%CI -45 to -6ms, p=0.007) and the TpTe c  shorter compared with acetazolamide (difference -11ms, 95%CI -21 to -1ms, p=0.028). Arrhythmias were rare and similar with all treatments.   Conclusions: In PH-patients with SDB, NOT reduces nocturnal heart rate and QT c  in the morning thus favorably modifying both prognostic markers.
Female Gender Is an Independent Predictor of Operative Mortality After Coronary Artery Bypass Graft Surgery
Authors: Ron Blankstein, R. Parker Ward, Morton Arnsdorf, Barbara Jones, You-Bei Lou, Michael Pine
Journal: Circulation (2005)

Background— Women have a higher operative mortality (OM) after coronary artery bypass graft (CABG) surgery than men. Suggested contributing factors have included women’s increased age, advanced disease, comorbidities, and smaller body surface area (BSA). It is unclear whether women’s increased risk factors fully account for this difference or whether female gender within itself is associated with increased OM. We attempted to determine whether, all other factors being equal, there is a significant difference in OM between men and women undergoing CABG. Methods and Results— We retrospectively reviewed a clinical database of 15,440 patients who underwent CABG at 31 Midwestern hospitals in 1999–2000. Each patient record consisted of &gt;400 data elements. Risk-adjusted mortality rates were computed using a predictive equation derived by stepwise logistic regression. Overall, women were older, had a higher incidence of diabetes and valvular disease, and were more likely to be presenting in shock. The OM for the entire population was 2.88% (women 4.24% versus men 2.23%, P &lt;0.0001). Lower BSA was found to be an independent predictor of increased mortality, and a direct inverse relationship between BSA and OM was noted. After adjusting for all comorbidities including BSA, female gender remained an independent predictor of increased mortality (risk-adjusted OM was 3.81% for women and 2.43% for men). Thus, whereas risk adjustment reduced women’s OM from 90% higher than men’s to 22% higher, a significant difference remained. Conclusions— In this contemporary data set from 31 Midwestern hospitals, female gender was an independent predictor of perioperative mortality, even after accounting for all comorbidities, including low BSA.
An ELISA based assay to detect activation of Rho family GTPases
Authors: Li Cheng, Kim Middleton, Ashley Davis
Journal: Cancer Research (2007)

2832   The Rho family of small GTPases, a branch of Ras superfamily protein, consists of at least 20 members, the most extensively characterized of which are the Rac1, RhoA and Cdc42 proteins. In common with all other small GTPases, the RhoA proteins act as molecular switches that transmit cellular signals through downstream effector proteins. This family mediates a wide range of cellular responses, including cytoskeleton reorganization, proliferation, tumorigenesis and tumor invasion. Overexpression of Rho proteins have been observed in many human tumor cell lines.  The Rho switch operates by alternating between an active, GTP-bound state and an inactive, GDP-bound state. Understanding the mechanisms that regulate activation / inactivation of the Rho GTPase is of obvious biological significance due to its critical role in tumorigenesis. The fact that many Rho family effector proteins will specifically recognize the GTP bound form of the protein has been exploited experimentally to develop an affinity purification assay to monitor Rho family protein activation.  Traditionally, Rho binding domains (RBD) of the Rho effector proteins were coupled to GST beads to precipitate the active Rho in a biological sample. This method suffers from the cost of time, the requirement for large amount of sample, inconsistent results, and incompatability with high throughput screen. To avoid these drawbacks, we developed and introduced G-LISATM assay - a novel ELISA based assay to detect the activation of Rho family GTPases (RhoA, Rac1, Cdc42).  This novel assay contains a 96 well plate coated with RBD domains of Rho effector proteins. The active Rho GTPases, but not inactive Rho from a biological sample will bind to the plate and be detected by incubation with a specific antibody. This ELISA based method is fast, convenient, requires little amount of sample and has more quantitative and consistent results and therefore will be a powerful tool to investigate Rho family activation. This method is suitable for high throughput screening a large number of cell or tissue samples for Rho family activation. Moreover, the RBD domain coupled 96 well plates can be used to screen compounds that inhibit or promote the interaction between a specific Rho family protein and its effectors. It is anticipated to be useful for drug discovery based on the fact that Rho family protein and downstream effector proteins are involved in many aspects of tumorigenesis.
Vitamins and Other Dietary Essentials.
Authors: Wallace Ruddell Aykroyd
Journal: JAMA (1933)

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Abstract 13944: Early Initiation of Remote Monitoring in CIED Patients is Associated with Reduced Mortality
Authors: Suneet Mittal, Jonathan Piccini, Fischer Avi, Jeff Snell, Nirav Dalal, Niraj Varma
Journal: Circulation (2014)

Introduction: Remote monitoring (RM) of cardiac implantable electronic devices (CIED) has been associated with reduced mortality. However, the relationship between the time from device implantation to initiation of RM and survival is unknown. Hypothesis: Following CIED implantation, early (within 91 days) initiation of remote monitoring will result in improved survival as compared to later initiation. Methods: Patients implanted with a St. Jude Medical ™ CIED (2008-2011) that participated in RM were included and data collected through Nov 2012. Patients enrolled in a clinical study were excluded. Age, gender, device type, and surveillance duration were ascertained using device tracking data. Weekly RM service utilization was determined from Merlin.net ™ . The index time was set as the time of first RM transmission (RM 1 ). The all-cause mortality incidence rate (MIR) was evaluated for each device type among patients with early (≤ 91 days) or late (&gt; 91 days, ≤ 52 weeks) time from device implant to RM 1 . All-cause survival was prospectively compared for each device type among patients with early or late time to RM 1 using Cox proportional hazards with gender as a covariate and stratification on age. Results: We evaluated 105,285 RM patients (71 ± 13 years, 64% male) with a PM (n= 46,758, 44%), ICD (n= 31,697, 30%), or CRT device (n= 26,830, 26%). The median time to RM 1 was 8 [4, 19] weeks. In comparison to patients with late RM 1 (median: 24 weeks), patients with early RM 1 (median 4 weeks) had lower MIR (4,114 vs 4,924 per 100k-pt-yrs, p&lt; 0.001) and greater survival (adjusted HR: 1.27 [CI: 1.22-1.32], p&lt; 0.001). This relationship held across each of the device types (Table.) Conclusion: Our data show that survival is higher in patients who have a shorter time between device implant and remote monitoring initiation, across all CIED device types. These data suggest RM should be initiated as soon as possible following device implantation.
Selenium Disrupts Estrogen Signaling by Altering Estrogen Receptor Expression and Ligand Binding in Human Breast Cancer Cells
Authors: Soo Ok Lee, Nagalakshmi Nadiminty, Xiu Xian Wu, Wei Lou, Yan Dong, Clement Ip, Sergio A. Onate, Allen C. Gao
Journal: Cancer Research (2005)

Abstract Cancer prevention studies suggest that selenium is effective in reducing the incidence of cancers including prostate, colon, and lung cancers. Previous reports showed that selenium inhibits premalignant human breast MCF-10AT1 and MCF10AT3B cell growth in vitro and reduces mammary tumor incidence after exposure to carcinogens in tumor models. Because estrogen is critical to the development and differentiation of estrogen target tissues, including the breast, the present study was designed to examine the effect of selenium on estrogen receptor (ER) expression and activation using methylseleninic acid (MSA), an active form of selenium in vitro. Selenium decreased the levels of expression of ERα mRNA and protein and reduced the binding of labeled estradiol to estrogen receptor in MCF-7 cells. Selenium inhibited the trans-activating activity of estrogen receptor in MCF-7 cells expressing functional estrogen receptor using a luciferase reporter construct linked to estrogen responsive element. Selenium decreased the binding of estrogen receptor to the estrogen responsive element site using an electrophoretic mobility gel shift assay. Selenium suppressed estrogen induction of the endogenous target gene c-myc. In contrast to the effect on ERα in MCF-7 cells, selenium increased ERβ mRNA expression in MDA-MB231 human breast cancer cells. Thus, differential regulation of ERα and ERβ in breast cancer cells may represent a novel mechanism of selenium action and provide a rationale for selenium breast cancer prevention trial.
Abstract 19837: The Presence of Pulmonary Hypertension Before Repair is an Independent Predictor of Late Atrial Arrhythmia in Adults With Transcatheter or Surgically Closed Asd Type Secundum.
Authors: Alexander Van De Bruaene, Marion Delcroix, Agnes Pasquet, Julie De Backer, Bernard Paelinck, Marielle Morissens, Werner Budts
Journal: Circulation (2010)
Coadministration of interleukin-18 and interleukin-12 induces a fatal inflammatory response in mice: critical role of natural killer cell interferon-γ production and STAT-mediated signal transduction
Authors: William E. Carson, Julie E. Dierksheide, Saad Jabbour, Mirela Anghelina, Page Bouchard, George Ku, Haixin Yu, Heinz Baumann, Manisha H. Shah, Megan A. Cooper, Joan Durbin, Michael A. Caligiuri
Journal: Blood (2000)
Rapid Intraoperative Molecular Characterization of Glioma
Authors: Ganesh M. Shankar, Joshua M. Francis, Mikael L. Rinne, Shakti H. Ramkissoon, Franklin W. Huang, Andrew S. Venteicher, Elliot H. Akama-Garren, Yun Jee Kang, Nina Lelic, James C. Kim, Loreal E. Brown, Sarah K. Charbonneau, Alexandra J. Golby, Chandra Sekhar Pedamallu, Mai P. Hoang, Ryan J. Sullivan, Andrew D. Cherniack, Levi A. Garraway, Anat Stemmer-Rachamimov, David A. Reardon, Patrick Y. Wen, Priscilla K. Brastianos, William T. Curry, Fred G. Barker, William C. Hahn, Brian V. Nahed, Keith L. Ligon, David N. Louis, Daniel P. Cahill, Matthew Meyerson
Journal: JAMA Oncology (2015)

Conclusive intraoperative pathologic confirmation of diffuse infiltrative glioma guides the decision to pursue definitive neurosurgical resection. Establishing the intraoperative diagnosis by histologic analysis can be difficult in low-cellularity infiltrative gliomas. Therefore, we developed a rapid and sensitive genotyping assay to detect somatic single-nucleotide variants in the telomerase reverse transcriptase (TERT) promoter and isocitrate dehydrogenase 1 (IDH1).This assay was applied to tissue samples from 190 patients with diffuse gliomas, including archived fixed and frozen specimens and tissue obtained intraoperatively. Results demonstrated 96% sensitivity (95% CI, 90%-99%) and 100% specificity (95% CI, 95%-100%) for World Health Organization grades II and III gliomas. In a series of live cases, glioma-defining mutations could be identified within 60 minutes, which could facilitate the diagnosis in an intraoperative timeframe.The genotyping method described herein can establish the diagnosis of low-cellularity tumors like glioma and could be adapted to the point-of-care diagnosis of other lesions that are similarly defined by highly recurrent somatic mutations.
A novel target for therapeutic inhibitors of hyaluronan synthesis - altered membrane topology of HA synthase in breast cancer cells
Authors: Tracey J. Brown, Lishanthi Udabage, Gary R. Brownlee
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

4611 

INTRODUCTION: The progression and invasion of breast cancer is often associated with the over-production of the glycosaminoglycan, hyaluronan (HA). HA is synthesized by a family of transmembrane glycosyltransferases termed HA synthases (HAS). Three eukaryotic HAS isoforms have been found and given the designations HAS1, HAS2 and HAS3. HA is produced by polymerization on the inner face of the plasma membrane; it is then extruded onto the extracellular surface of the cell. There is a direct correlation between HAS2 expression and the progression of breast cancer in vitro . The importance of HAS2 in both the initiation and progression of breast cancer was substantiated when antisense ablation of HAS2 in a highly invasive breast cancer cell line resulted in a 97% inhibition of cell invasiveness. When the HAS2 knock-out cancer cells were implanted into nude mice, tumors did not initiate highlighting the potential therapeutic value of inhibiting a functional hyaluronan synthase in the malignant state. METHODOLOGY: Therapeutic antibodies were developed by designing immunizing peptides to several separate regions of the proposed HAS tertiary structure. Two polyclonal antibodies were raised to predicted cytosolic domains (IN-1 & IN-2) and the third to a putative extracellular domain (EX-1) of the HAS protein. The effect of the HAS antibodies on cell proliferation and hyaluronan synthesis was evaluated in human dermal fibroblasts (DF) and 2 human breast cancer cell lines (MDA-MB-468 and MDA-MB-231) after the cells were cultured in the presence of varying concentrations of each affinity purified HAS antibody. The cellular location of each reactive epitope was determined by FACS and immunohistochemistry of both permeabilized (P) and non-permeabilzed (NP) DF and breast cancer cells. RESULTS: On NP cells antibodies against either IN-1 or IN-2 were non-reactive with dermal fibroblasts whereas anti-EX-1 reacted positively. In both breast cancer cell lines antibodies directed to EX-1 and IN-2 reacted with NP cells, indicating that the epitope for IN-2 localized to the extracellular domain of the HAS. In DF, anti-EX-1 inhibited HA synthesis and induced cell kill whereas antibodies to IN-1 or IN-2 did not. In the malignant state antibodies to EX-1 and also IN-2 inhibited HA synthesis and induced cell kill, whereas anti-IN-1 had no effect. CONCLUSIONS: The HA synthase of non-malignant cells appears to be localized consistent with the predicted topology. In contrast, breast cancer cells appear to extracellularly express what is predicted to be an intracellular epitope suggesting that the membrane topology of HAS is altered in the malignant state. These data warrants further evaluation of inhibitory antibodies specific to this novel epitope which could potentially act as therapeutic inhibitors of hyaluronan synthesis, thereby leading to new therapies for breast cancer.
Abstract 02: Population Strategies to Decrease Sodium Intake: A Global Cost-Effectiveness Analysis
Authors: Michael Webb, Saman Fahimi, Gitanjali M Singh, Shahab Khatibzadeh, Renata Micha, John Powles, Dariush Mozaffarian
Journal: Circulation (2014)

Background: Excess sodium intake is a major risk factor for CVD globally. Yet, the cost-effectiveness of policy interventions to reduce sodium consumption in every country has not been quantified. Methods: We characterized global sodium intakes, blood pressure (BP) levels, effects of sodium on BP, and CVD rates, each by age and sex in 187 countries based on the 2010 Global Burden of Diseases study. Nation-specific costs of a policy that combined education with targeted industry agreements to reduce sodium were estimated using the WHO NCD Costing Tool. Nation-specific impacts on mortality and disability-adjusted life years (DALYs) were modeled using comparative risk assessment, based on various scenarios including 10%, 30%, 1 g/d, and 3 g/d achieved sodium reductions over 10 yrs. Cost-effectiveness (CE) was evaluated as PPP-adjusted international $ per DALY saved over 10 yrs. Results: Worldwide, a 10% sodium reduction within each country was projected to avert an average of 5,655,000 CVD-related DALYs/year, at an average cost of 1.11 international dollars per capita over the 10 yr intervention. The average CE ratio was I$207/DALY. Across 21 world regions, sodium reduction would be most CE in South Asia and East/Southeast Asia (each I$120/DALY); across 187 countries, the most CE were Moldova (I$9.89/DALY), Azerbaijan (I$12.82/DALY), and Uzbekistan (I$12.85/DALY). The least CE region was Australia/New Zealand (I$922/DALY), although this CE was still substantially below the usual threshold to define an intervention as CE (3.0 GDP per capita). 99% of the world's population live in countries in which the intervention had a CE ratio &lt; 1.0 GDP per capita, and 95% in countries with a CE ratio &lt; 0.1 GDP per capita - far below standard acceptable CE ratios of 3.0 GDP per capita. Conclusions: National education and industry-agreement strategies to reduce dietary sodium would have substantial impacts on CVD and be extremely cost-effective in nearly every country worldwide. CE of 10% reduction intervention: GDP/capita per DALY
HIV patients benefit from dual drug treatment
Authors: Scott Gottlieb
Journal: BMJ (2001)

Some patients with HIV infection are more likely to benefit from treatment using a combination of two enzyme inhibitors than with either of the drugs on its own, a new study has reported.

For patients who have failed nucleoside analogue therapy, the protease inhibitor nelfinavir combined with the non-nucleoside reverse transcriptase inhibitor efavirenz is more effective than either of the drugs alone, said a report from Dr Mary Albrecht …