tbuckley/cabot-search huggingface dataset:
Relationship between urinary sialylated saccharides, serum amyloid A protein, and C-reactive protein in rheumatoid arthritis and systemic lupus erythematosus.
Authors: C.P Maury, A.M Teppo, O Wegelius
Journal: Annals of the Rheumatic Diseases (1982)

The urinary excretion of sialic-acid-containing oligosaccharides, total sialic acid, serum amyloid A protein (SAA), and C-reactive protein (CRP) has been studied in 48 patients with rheumatoid arthritis (RA) and in 17 patients with systemic lupus erythematosus (SLE). Linear regression analysis revealed a close positive correlation between serum SAA and CRP levels in both RA (r = 0.71, p less than 0.001) and SLE (r = 0.86, p less than 0.001). The urinary excretion of sialyl lactose showed a positive correlation with the serum levels of SAA and CRP in RA (r = 0.45 and r = 0.45, respectively, p less than 0.01) but not in SLE (r = 0.05 and r = 0.10 respectively). Changes in serum total sialic acid levels paralleled those in CRP and SAA in RA as well as in SLE. Patients with very active RA had higher urinary sialyl oligosaccharide excretion (p less than 0.001), higher CRP levels (p less than 0.01), and higher SAA levels ( p less than 0.05) than those with moderately active disease.
Black Carbon Exposures, Blood Pressure, and Interactions with Single Nucleotide Polymorphisms in MicroRNA Processing Genes
Authors: Elissa H. Wilker, Andrea Baccarelli, Helen Suh, Pantel Vokonas, Robert O. Wright, Joel Schwartz
Journal: Environmental Health Perspectives (2010)

Black carbon (BC) is a marker of traffic pollution that has been associated with blood pressure (BP), but findings have been inconsistent. MicroRNAs (miRNAs) are emerging as key regulators of gene expression, but whether polymorphisms in genes involved in processing of miRNAs to maturity influence susceptibility to BC has not been elucidated.We investigated the association between BC and BP, as well as potential effect modification by single nucleotide polymorphisms (SNPs) in miRNA processing genes.Repeated measures analyses were performed using data from the VA Normative Aging Study. Complete covariate data were available for 789 participants with one to six study visits between 1995 and 2008. In models of systolic and diastolic BP, we examined SNP-by-BC interactions with 19 miRNA-related variants under recessive models of inheritance. Mixed-effects models were adjusted for potential confounders including clinical characteristics, lifestyle, and meteorologic factors.A 1-SD increase in BC (0.415 microg/m(3)) was associated with 3.04 mmHg higher systolic (95% confidence interval (CI), 2.29-3.79) and 2.28 mmHg higher diastolic BP (95% CI, 1.88-2.67). Interactions modifying BC associations were observed with SNPs in the DICER, GEMIN4, and DiGeorge critical region-8 (DGCR8) genes, and in GEMIN3 and GEMIN4, predicting diastolic and systolic BP, respectively.We observed evidence of effect modification of the association between BP and 7-day BC moving averages by SNPs associated with miRNA processing. Although the mechanisms underlying these associations are not well understood, they suggest a role for miRNA genesis and processing in influencing BC effects.
Mammographic Breast Density and Family History of Breast Cancer
Authors: Elad Ziv, John Shepherd, Rebecca Smith-Bindman, Karla Kerlikowske
Journal: JNCI Journal of the National Cancer Institute (2003)

The association between mammographic breast density and breast cancer risk may be the result of genetic and/or environmental factors that determine breast density. We reasoned that if the genetic factors that underlie breast density increase breast cancer risk, then breast density should be associated with family history of breast cancer. Therefore, we determined the association between mammographic density and family history of breast cancer among women in the San Francisco Mammography Registry. Mammographic density was classified using the four BI-RADS criteria: 1 = almost entirely fatty, 2 = scattered fibroglandular tissue, 3 = heterogeneously dense, and 4 = extremely dense. We adjusted for age, body mass index, hormone replacement therapy use, menopause status, and personal history of breast cancer. Compared with women with BI-RADS 1 readings, women with higher breast density were more likely to have first-degree relatives with breast cancer (BI-RADS 2, odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.96 to 1.89; BI-RADS 3, OR = 1.70, 95% CI = 1.19 to 2.40; BI-RADS 4, OR = 1.70, 95% CI = 1.05 to 2.71). Thus, the genetic factors that determine breast density may determine breast cancer risk.
Antibodies of the IgG, IgM, and IgA classes in newborn and adult sera reactive with gram-negative bacteria
Authors: Irun R. Cohen, Leslie C. Norins
Journal: Journal of Clinical Investigation (1968)

Umbilical cord serum and adult serum antibodies reactive with heat-stable somatic antigens of Gram-negative bacteria (Neisseria gonorrhoeae, Escherichia coli, and Salmonella typhosa) were assayed by using an indirect fluorescent antibody test. Reactive IgG, IgM, and IgA antibodies were identified by using fluoresceinconjugated antisera specific for these immunoglobulin classes.IgG antibody titers in cord serum approximated those found in the corresponding maternal sera. IgM and IgA antibodies were present in adult sera but were not demonstrable or were present only in small amounts in cord sera. The presence of IgG and IgM antibodies reactive with Gram-negative bacteria was confirmed by the testing of purified 7S and 19S fractions. In addition, both IgG and IgM reactivities were inhibited by the prior incubation of serum with purified specific lipopolysaccharide preparations. The ubiquity and magnitude of these natural IgG antibodies in the sera of both adults and neonates have apparently eluded detection in previous studies. The use of bactericidal and agglutination tests, which are apparently more sensitive to the presence of IgM than to IgG antibodies, may account for the failure of previous studies to detect adult and cord IgG antibodies reactive with somatic antigens of Gram-negative bacteria. The presence of these IgG antibodies may be correlated with the resistance to infection demonstrated by most newborns as they are challenged by the septic extrauterine environment.
Effects of reducing beta-lactam antibiotic pressure on intestinal colonization of antibiotic-resistant gram-negative bacteria
Authors: Saskia Nijssen, Ad Fluit, David van de Vijver, Janetta Top, Rob Willems, Marc J. M. Bonten
Journal: Intensive Care Medicine (2009)

We determined the effects of two antibiotic policies (predominance of either β-lactam antibiotics or fluroquinolones) on acquisition with third-generation cephalosporin-resistant Enterobacteriaceae (CRE) and fluoroquinolone-resistant CRE (FCRE) in two ICUs, with monitoring of other variables that may influence acquisition. After an 8-month baseline period, units were randomized to a predominant β-lactam antibiotic regimen (weekly cycling of ceftriaxone, amoxicillin–clavulanic acid and fluroquinolones) or a fluoroquinolone regimen for 3 months, with cross-over for another 3 months. Acquisition of CRE and FCRE was determined by microbiological surveillance. During baseline, acquisition rates for CRE and FCRE were 14/1,000 and 2/1,000 patient days at risk, respectively. Cross-transmission of CRE accounted for ≤25% of acquisitions, and CRE acquisition was associated with the use of β-lactam antibiotics (amoxicillin–clavulanic acid in particular). As compared to baseline, β-lactam antibiotic use [in defined daily dose (DDD)/1,000 patient days] was reduced from 854 to 526 (−39%) and 555 (−35%) during both intervention periods. Fluoroquinolone use was increased from 150 and 129 DDD/1,000 patient days in baseline and the β-lactam period to 514 DDD/1,000 patient days (+243%) in the fluoroquinolone period. Reductions in β-lactam use were not associated with reduced CRE acquisition [adjusted HRs were 1.0 (95% CR: 0.5–2.2) and 1.1 (95% CI: 0.5–2.5) during both periods, respectively]. Increased use of fluoroquinolones was associated with increased acquisition of FCRE [adjusted HR 4.1 (95% CI: 1.4–11.9; p < 0.01]. Infection control variables remained comparable during all periods. A 35–39% reduction of β-lactam exposure was not associated with reduced acquisition of CRE, whereas a 243% increase of fluoroquinolone use increased acquisition of FCRE.
Panobinostat in Patients With Relapsed/Refractory Hodgkin's Lymphoma After Autologous Stem-Cell Transplantation: Results of a Phase II Study
Authors: Anas Younes, Anna Sureda, Dina Ben-Yehuda, Pier Luigi Zinzani, Tee-Chuan Ong, H. Miles Prince, Simon J. Harrison, Mark Kirschbaum, Patrick Johnston, Jennifer Gallagher, Christophe Le Corre, Angela Shen, Andreas Engert
Journal: Journal of Clinical Oncology (2012)

Hodgkin's lymphoma (HL) has no standard of care for patients who are relapsed or refractory to autologous stem-cell transplantation (ASCT). This phase II study examined safety and activity of panobinostat in this population.Panobinostat 40 mg was administered orally three times per week. The primary end point was objective response rate (ORR) based on investigator assessment of radiologic imaging. Secondary end points included ORR by independent central review, time to response (TTR), duration of response (DOR), progression-free survival (PFS), overall survival, and safety. Exploratory biomarker analyses were performed.The 129 treated patients (median age, 32 years; range, 18 to 75 years) were heavily pretreated with a median of four (range, two to seven) prior systemic regimens, and 41% did not respond to the regimen immediately preceding panobinostat. Tumor reductions occurred in 96 patients (74%). Objective response was achieved by 35 patients (27%), including 30 (23%) partial responses and five (4%) complete responses. The median TTR was 2.3 months, median DOR was 6.9 months, and median PFS was 6.1 months. The estimated 1-year overall survival rate was 78%. Common nonhematologic adverse events (AEs)-diarrhea, nausea, vomiting, and fatigue-were generally grade 1 and 2. Most common grade 3 and 4 hematologic AEs-thrombocytopenia, anemia, and neutropenia-were manageable. Early reductions in thymus and activation-regulated chemokine were observed in patients achieving complete or partial response.In the largest, prospective, multicenter, international trial conducted in heavily pretreated patients with HL who relapsed or were refractory to ASCT, panobinostat monotherapy demonstrated antitumor activity, resulting in durable responses.
Prediction, Progression, and Outcomes of Chronic Kidney Disease in Older Adults
Authors: Sharon Anderson, Jeffrey B. Halter, William R. Hazzard, Jonathan Himmelfarb, Frances McFarland Horne, George A. Kaysen, John W. Kusek, Susan G. Nayfield, Kenneth Schmader, Ying Tian, John R. Ashworth, Charles P. Clayton, Ryan P. Parker, Erika D. Tarver, Nancy F. Woolard, Kevin P. High
Journal: Journal of the American Society of Nephrology (2009)

Chronic kidney disease is a large and growing problem among aging populations. Although progression of chronic kidney disease to end-stage renal disease (ESRD) is a costly and important clinical event with substantial morbidity, it appears less frequently in aging people compared with cardiovascular mortality. The measurement of kidney function and management of kidney disease in older individuals remain challenging, partly because the pathophysiologic mechanisms underlying age-related decline in kidney function, the interactions between age and other risk factors in renal progression, and the associations of chronic kidney disease with other comorbidities in older people are understudied and poorly understood. The Association of Specialty Professors, the American Society of Nephrology, the American Geriatrics Society, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases held a workshop, summarized in this article, to review what is known about chronic kidney disease, identify research gaps and resources available to address them, and identify priority areas for future research. Answers to emerging research questions will support the integration of geriatrics and nephrology and thus improve care for older patients at risk for chronic kidney disease.
Mutations in SECISBP2 result in abnormal thyroid hormone metabolism
Authors: Alexandra M Dumitrescu, Xiao-Hui Liao, Mohamed S Y Abdullah, Joaquin Lado-Abeal, Fathia Abdul Majed, Lars C Moeller, Gerard Boran, Lutz Schomburg, Roy E Weiss, Samuel Refetoff
Journal: Nature Genetics (2005)
AMINO ACID MIXTURES EFFECTIVE PARENTERALLY FOR LONG CONTINUED PLASMA PROTEIN PRODUCTION. CASEIN DIGESTS COMPARED
Authors: S. C. Madden, R. R. Woods, F. W. Shull, G. H. Whipple
Journal: The Journal of Experimental Medicine (1944)

When blood plasma proteins are depleted by bleeding with return of red cells suspended in saline (plasmapheresis) it is possible to bring dogs to a steady state of hypoproteinemia and a constant level of plasma protein production if the diet nitrogen intake is controlled and limited. Such dogs are outwardly normal but have a lowered resistance to infection and to certain intoxications. The ten growth essential amino acids of Rose plus glycine will maintain nitrogen balance and produce as much new plasma protein as will good diet proteins. This good utilization is demonstrated over periods of several months when the amino acids are given either orally or parenterally. There is no evidence of toxicity in general nor to unnatural forms of these synthetic amino acids in particular. Given parenterally appropriate mixtures of these amino acids are well tolerated even upon rapid injection. The minimal daily requirements for a 10 kilo dog may be given intravenously in 10 minutes without reaction. Subcutaneously a 10 per cent solution may be given rapidly without reaction. Among various mixtures tested Vt approximates a minimum for a 10 kilo dog. It contains in grams (dl-threonine 0.7, dl-valine 1.5, l-(-) leucine 1.5, dl-isoleucine 1.4, dl-lysine hydrochloride 1.5, l(-) tryptophane 0.4, dl-phenylalanine 1.0, dl-methionine 0.6, l(+)-histidine hydrochloride 0.5, l(+)-arginine hydrochloride 0.5, and glycine 1.0. The presence of glycine improves tolerance to rapid intravenous injection, but excess glycine does not improve utilization of the mixture. Over a long period this mixture appears suboptimal in quantity. Doubled it is more than ample. Of two casein digests tested the one prepared by enzymatic hydrolysis provided good nitrogen retention and fairly good plasma protein production but was much less tolerable upon intravenous injection than certain mixtures of pure amino acids. The other one prepared by acid hydrolysis and tryptophane fortification afforded bare nitrogen equilibrium and produced virtually no plasma protein. Skin lesions observed after 10 to 20 weeks of synthetic diet probably reflect a deficiency of some member or members of the vitamin B(2) group. A persistent slight weight loss in the face of a strongly positive nitrogen balance may accompany this deficiency.
Using Glycosylated Hemoglobin to Define the Metabolic Syndrome in United States Adults
Authors: Kwok Leung Ong, Annette W.K. Tso, Karen S.L. Lam, Stacey S. Cherny, Pak Chung Sham, Bernard M.Y. Cheung
Journal: Diabetes Care (2010)

To compare the use of GHb and fasting plasma glucose (FPG) to define the metabolic syndrome (MetS).Data from the U.S. National Health and Nutrition Examination Survey 1999-2006 were used. MetS was defined using the consensus criteria in 2009. Raised blood glucose was defined as either FPG >or=100 mg/dl (5.6 mmol/l) or GHb >or=5.7%.In 2003-2006, there was 91.3% agreement between GHb and FPG when either was used to define MetS. The agreement was good irrespective of age, sex, race/ethnicity, BMI, and diabetes status (>or=87.4%). Similar results were found in 1999-2002. Among subjects without diabetes, only the use of GHb alone, but not FPG, resulted in significant association with cardiovascular diseases (odds ratio 1.45, P = 0.005).Using GHb instead of FPG to define MetS is feasible. It also identifies individuals with increased cardiovascular risk.
Integrated analysis of breast cancer cell lines reveals unique signaling pathways
Authors: Laura M Heiser, Nicholas J Wang, Carolyn L Talcott, Keith R Laderoute, Merrill Knapp, Yinghui Guan, Zhi Hu, Safiyyah Ziyad, Barbara L Weber, Sylvie Laquerre, Jeffrey R Jackson, Richard F Wooster, Wen Kuo, Joe W Gray, Paul T Spellman
Journal: Genome biology (2009)

Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EgfR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes.We were interested in identifying subnetworks within the EgfR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EgfR-MAPK signaling. This model was composed of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype-specific subnetworks, including one that suggested Pak1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that Pak1 over-expressing cell lines would have increased sensitivity to Mek inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three Mek inhibitors. We found that Pak1 over-expressing luminal breast cancer cell lines are significantly more sensitive to Mek inhibition compared to those that express Pak1 at low levels. This indicates that Pak1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to Mek inhibitors.All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.
Report of the National Heart, Lung, and Blood Institute Working Group on the Translation of Cardiovascular Molecular Imaging
Authors: Denis B. Buxton, Melissa Antman, Narasimhan Danthi, Vasken Dilsizian, Zahi A. Fayad, Mario J. Garcia, Michael R. Jaff, Michael Klimas, Peter Libby, Matthias Nahrendorf, Albert J. Sinusas, Samuel A. Wickline, Joseph C. Wu, Robert O. Bonow, Ralph Weissleder
Journal: Circulation (2011)
Doctors and Management in the National Health Service, by Gordon Marnoch Really Managing Health Care, by Valerie Iles The Clinical Directorate, ed Noel Austin, Sue Dopson
Authors: J. A Shirley
Journal: BMJ (1997)

Gordon Marnoch Open University Press, £14.99, pp 138 ISBN 0 335 19344 7

Valerie Iles Open University Press, £15.99, pp 191 ISBN 0 335 19414 1

Ed Noel Austin, Sue Dopson Radcliffe Medical Press, £18.50, pp 174 ISBN 1 85775 037 3

Since the NHS reforms in 1991 doctors have been much more closely involved in managing the health service. As a result, there is a need for information about what being a doctor manager means, the theories behind managing in practice, and how to manage effectively. …
Adipose Tissue Biology and Cardiomyopathy
Authors: Aslan T. Turer, Joseph A. Hill, Joel K. Elmquist, Philipp E. Scherer
Journal: Circulation Research (2012)

It is epidemiologically established that obesity is frequently associated with the metabolic syndrome and poses an increased risk for the development of type 2 diabetes mellitus and cardiovascular disease. The molecular links that connect the phenomenon of obesity, per se, with insulin resistance and cardiovascular disease are still not fully elucidated. It is increasingly apparent that fully functional adipose tissue can be cardioprotective by reducing lipotoxic effects in other peripheral tissues and by maintaining a healthy balance of critical adipokines, thereby allowing the heart to maintain its full metabolic flexibility. The present review highlights both basic and clinical findings that emphasize the complex interplay of adipose tissue physiology and adipokine-mediated effects on the heart exerted by either direct effects on cardiac myocytes or indirect actions via central mechanisms through sympathetic outflow to the heart.
Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity
Authors: Anne Vrieze, Carolien Out, Susana Fuentes, Lisanne Jonker, Isaie Reuling, Ruud S. Kootte, Els van Nood, Frits Holleman, Max Knaapen, Johannes A. Romijn, Maarten R. Soeters, Ellen E. Blaak, Geesje M. Dallinga-Thie, Dorien Reijnders, Mariëtte T. Ackermans, Mireille J. Serlie, Filip K. Knop, Jenst J. Holst, Claude van der Ley, Ido P. Kema, Erwin G. Zoetendal, Willem M. de Vos, Joost B.L. Hoekstra, Erik S. Stroes, Albert K. Groen, Max Nieuwdorp
Journal: Journal of Hepatology (2013)
Influence of Dextran Infusion on the Pulmonary Hypertensive Effect of Concentrated Saline
Authors: RAYMOND C. READ, JAMES A. VICK, MAURICE E. MEYER
Journal: Circulation Research (1961)

Low-molecular-weight dextran, which is known to prevent the sludging of blood cells seen in shock, has recently been reported to reduce the toxicity of concentrated radiopaque agents. Experiments have been performed to determine whether this latter effect applies to other hyperosmotic solutions. An attempt was made to delineate the mechanism involved. One ml./Kg. of 15 per cent NaCl was rapidly injected into dogs before and after infusion of 10 ml./Kg. of 15 per cent low-molecular-weight dextran. This treatment significantly reduced the usual pulmonary-hypertensive response. However, other dextran preparations, plasma, and blood were equally effective. Moreover, previous infusion of isotonic saline also conferred immunity when given at a rate sufficient to raise left-atrial pressure. Let't-atrial hypertension produced independently of changes in blood volume evoked similar amelioration. If this latter change was prevented by concurrent bleeding, none of the infusions was beneficial. Vice versa, a fall in left-atrial pressure was associated with an accentuated reaction to 15 per cent NaCl. Microscopic examination of the intact lung during protection showed that red-cell agglutination still occurred from concentrated saline, but the small vessels were dilated. It is concluded that low-molecular-weight dextran and other infusions provide prophylaxis against the pulmonary-hypertensive effects of concentrated saline by reducing the susceptibility of the lung to microembolism through the development of left-atrial hypertension.
Inhaled treprostinil therapy in patients with pulmonary hypertension and parenchymal lung disease
Authors: Arlene Schiro, Aaron Waxman
Journal: European Respiratory Journal (2011)

The treatment of patients with Parenchymal Lung Disease (PLD) and Pulmonary Hypertension (PH) is challenging. PLD is characterized by an imbalance between alveolar ventilation and pulmonary blood flow. The ability to deliver therapy to areas of lung that are well ventilated would utilize preserved V/Q matching and improve drug delivery. This would reduce undesirable alterations in perfusion caused by a systemic vasodilator and provide a more effective way of treating these patients. We examined the response of patients with PLD and PH receiving Inhaled Treprostinil. We followed eight patients with NYHA Functional Class IIIB to IV symptoms with a mean PAP >25mmHg and PCWP of