tbuckley/cabot-search huggingface dataset:
Primary Results of the Patient-Centered Disease Management (PCDM) for Heart Failure Study
Authors: David B. Bekelman, Mary E. Plomondon, Evan P. Carey, Mark D. Sullivan, Karin M. Nelson, Brack Hattler, Connor F. McBryde, Kenneth G. Lehmann, Katherine Gianola, Paul A. Heidenreich, John S. Rumsfeld
Journal: JAMA Internal Medicine (2015)

IMPORTANCE Heart failure (HF) has a major effect on patients' health status, including their symptom burden, functional status, and health-related quality of life.OBJECTIVE To determine the effectiveness of a collaborative care patient-centered disease management (PCDM) intervention to improve the health status of patients with HF. DESIGN, SETTING, AND PARTICIPANTSThe Patient-Centered Disease Management (PCDM) trial was a multisite randomized clinical trial comparing a collaborative care PCDM intervention with usual care in patients with HF.A population-based sample of 392 patients with an HF diagnosis from 4 Veterans Affairs centers who had a Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score of less than 60 (heavy symptom burden and impaired functional status and quality of life) were enrolled between May 2009 and June 2011. INTERVENTIONSThe PCDM intervention included collaborative care by a multidisciplinary care team consisting of a nurse coordinator, cardiologist, psychiatrist, and primary care physician; home telemonitoring and patient self-management support; and screening and treatment for comorbid depression. MAIN OUTCOMES AND MEASURESThe primary outcome was change in the KCCQ overall summary score at 1 year (a 5-point change is clinically significant).Mortality, hospitalization, and depressive symptoms (Patient Health Questionnaire 9) were secondary outcomes.RESULTS There were no significant differences in baseline characteristics between patients randomized to the PCDM intervention (n = 187) vs usual care (n = 197); baseline mean KCCQ overall summary scores were 37.9 vs 36.9 (P = .48).There was significant improvement in the KCCQ overall summary scores in both groups after 1 year (mean change, 13.5 points in each group), with no significant difference between groups (P = .97).The intervention was not associated with greater improvement in the KCCQ overall summary scores when the effect over time was estimated using 3-month, 6-month, and 12-month data (P = .74).Among secondary outcomes, there were significantly fewer deaths at 1 year in the intervention arm (8 of 187 [4.3%]) than in the usual care arm (19 of 197 [9.6%]) (P = .04).Among those who screened positive for depression, there was a greater improvement in the Patient Health Questionnaire 9 scores after 1 year in the intervention arm than in the usual care arm (2.1 points lower, P = .01).There was no significant difference in 1-year hospitalization rates between the intervention arm and the usual care arm (29.4% vs 29.9%, P = .87).CONCLUSIONS AND RELEVANCE This multisite randomized trial of a multifaceted HF PCDM intervention did not demonstrate improved patient health status compared with usual care.
Associations of Bone Mineral Density and Lead Levels in Blood, Tibia, and Patella in Urban-Dwelling Women
Authors: Keson Theppeang, Thomas A. Glass, Karen Bandeen-Roche, Andrew C. Todd, Charles A. Rohde, Jonathan M. Links, Brian S. Schwartz
Journal: Environmental Health Perspectives (2008)

The objective of this study was to evaluate the relations between bone mineral density (BMD) and lead in blood, tibia, and patella and to investigate how BMD modifies these lead biomarkers in older women.In this study, we used cross-sectional analysis.We studied 112 women, 50-70 years of age, including both whites and African Americans, residing in Baltimore, Maryland.We measured lumbar spine BMD, blood and bone lead by dual energy X-ray absorptiometry, anodic stripping voltammetry, and (109)Cd-induced K-shell X-ray fluorescence, respectively. We measured vitamin D receptor and apolipoprotein E (APOE) genotypes using standard methods.Mean (+/- SD) BMD and lead levels in blood, tibia, and patella were 1.02+/-0.16 g/cm(2), 3.3+/-2.2 microg/dL, 19.7+/-13.2 microg/g, and 5.7+/-15.3 microg/g, respectively. In adjusted analysis, higher BMD was associated with higher tibia lead levels (p=0.03). BMD was not associated with lead levels in blood or patella. There was evidence of significant effect modification by BMD on relations of physical activity with blood lead levels and by APOE genotype on relations of BMD with tibia lead levels. There was no evidence that BMD modified relations between tibia lead or patella lead and blood lead levels.We believe that BMD represents the capacity of bone that can store lead, by substitution for calcium, and thus the findings may have relevance for effect-size estimates in persons with higher BMD.The results have implications for changes in lead kinetics with aging, and thus the related risk of health effects associated with substantial early- and midlife lead exposure in older persons.
T cell recognition of self-human histocompatibility leukocyte antigens (HLA)-DR peptides in context of syngeneic HLA-DR molecules.
Authors: Z Liu, Y K Sun, Y P Xi, P Harris, N Suciu-Foca
Journal: The Journal of Experimental Medicine (1992)

It has been suggested that self major histocompatibility complex (MHC) peptides bound to self MHC molecules may be involved in the intrathymic induction of self tolerance. We studied the antigenicity of synthetic peptides derived from the first domain of DR beta 1*0101 chain in a DR beta 1*0101 responder. We found that a peptide corresponding to residues 21-42 of the beta chain could elicit the proliferation of autoreactive T cells. A T cell line (TCL-SUN) and 7 of 9 T cell clones (TCC) derived from TCL-SUN specifically recognized peptide 21-42 in the presence of APCs carrying the DR beta 1*0101 allele. DR beta 1*0101 positive APCs stimulated the TCCs in the absence of peptide, although the magnitude of the response was much lower than in cultures with peptide. This suggests that self DR1 molecules are continuously processed into peptides that are presented by the DR1 molecules on the surface of the cells. The data indicate that some T cells whose TCR binds to self MHC peptides presented by self MHC molecules are not deleted, although their ligand is continuously present. TCCs specific for peptide 21-42 presented in the context of DR1 were also stimulated by cells heterozygous for DR beta 1*0301 and 1601, indicating that some DR peptide-specific autoreactive T cells participate in alloreactivity.
Missing band 7 membrane protein in two patients with high Na, low K erythrocytes.
Authors: W M Lande, P V Thiemann, W C Mentzer
Journal: Journal of Clinical Investigation (1982)

We investigated the erythrocyte membrane proteins of two patients with congenital hemolytic anemia due to increased permeability of the erythrocyte membrane to Na and K (hereditary stomatocytosis and cryohydrocytosis). One-dimensional sodium dodecyl sulfate (SDS) gel electrophoresis resolved the band 7 erythrocyte membrane proteins into three components with approximate molecular weights of 30,000, 28,000, and 26,000. The 28,000-dalton component was decreased in both patients with permeability disorders. Two-dimensional electrophoresis (nonequilibrium pH gradient electrophoresis in the first dimension combined with SDS gel electrophoresis in the first dimension combined with SDS gel electrophoresis in the second dimension) resolved the 28,000-dalton component from normal erythrocyte membranes into two proteins with different isoelectric points, designated 22 x 8 and 60 x 8. In the patients with hereditary stomatocytosis and cryohydrocytosis, 22 x 8 was completely absent, whereas 60 x 8 was detected as usual. In contrast, all the band 7 proteins (including 22 x 8) were invariably present in a survey of normal subjects and reticulocytosis controls. The unique finding of a missing band 7 protein in the patients with hereditary stomatocytosis and cryohydrocytosis raises the possibility that the absence of this protein is responsible for the increased Na and K permeability in these disorders.
Prognostic Significance of Gene Expression Profiles of Metastatic Neuroblastomas Lacking MYCN Gene Amplification
Authors: Shahab Asgharzadeh, Roger Pique-Regi, Richard Sposto, Hong Wang, Yujun Yang, Hiroyuki Shimada, Katherine Matthay, Jonathan Buckley, Antonio Ortega, Robert C. Seeger
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: The aggressiveness of metastatic neuroblastomas that lack MYCN gene amplification varies with age—they are least aggressive when diagnosed in patients younger than 12 months and most aggressive when diagnosed in patients older than 24 months. However, age at diagnosis is not always associated with patient survival. We examined whether molecular classification of metastatic neuroblastomas without MYCN gene amplification at diagnosis using gene expression profiling could improve the prediction of risk of disease progression. Methods: We used Affymetrix microarrays to determine the gene expression profiles of 102 untreated primary neuroblastomas without MYCN gene amplification obtained from children whose ages at diagnosis ranged from 0.1 to 151 months. A supervised method using diagonal linear discriminant analysis was devised to build a multigene model for predicting risk of disease progression. The accuracy of the model was evaluated using nested cross-validations, permutation analyses, and gene expression data from 15 additional tumors obtained at disease progression. Results: An expression profile model using 55 genes defined a tumor signature that distinguished two groups of patients from among those older than 12 months at diagnosis and clinically classified as having high-risk disease, those with a progression-free survival (PFS) rate of 16% (95% confidence interval [CI] = 8% to 28%), and those with a PFS rate of 79% (95% CI = 57% to 91%) ( P <.01). These tumor signatures also identified two groups of patients with PFS of 15% (95% CI = 7% to 27%) and 69% (95% CI = 40% to 86%) ( P <.01) from among patients who were older than 18 months at diagnosis. The gene expression signature of untreated molecular high-risk tumors was also present in progressively growing tumors. Conclusion: Gene expression signatures of tumors obtained at diagnosis from patients with clinically indistinguishable high-risk, metastatic neuroblastomas identify subgroups with different outcomes. Accurate identification of these subgroups with gene expression profiles may facilitate development, implementation, and analysis of clinical trials aimed at improving outcome.
A Cholesteryl Ester Transfer Protein Gene Mutation and Vascular Disease in Dialysis Patients
Authors: HIDEKI KIMURA, FUMITAKE GEJYO, TOMOKO YAMAGUCHI, SATORU SUZUKI, TOSHIO IMURA, RYOICHI MIYAZAKI, MASAAKI ARAKAWA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Among patients undergoing maintenance hemodialysis, a decreased high-density lipoprotein cholesterol (HDL-C) concentration is among the most common abnormalities of lipid metabolism and apparently is an independent risk factor for vascular disease. A common missense mutation of cholesteryl ester transfer protein gene, D442G (Asp 442 to Gly), increases HDL-C levels through the reduced activity of cholesteryl ester transfer from HDL to VLDL, but the mutation also may lead to reduced activity of reverse cholesterol transport. To investigate the effect of the D442G polymorphism on atherosclerotic complications in dialysis patients, the genotype and allele frequency of the polymorphism were determined in 414 unselected dialysis patients and 220 control subjects, and postprandial serum lipid levels were measured in the dialysis patients. A similar genotype distribution was found between hemodialysis patients and healthy control subjects, and in dialysis patients with and without vascular disease. Serum levels of total cholesterol and HDL-C did not differ between patients with and without the mutation and in patients with and without vascular disease. However, patients with sub-median HDL-C levels (&lt;45 mg/dl) had an independent odds ratio of 1.8 for vascular disease (95% confidence interval, 1.04 to 3.2; P &lt; 0.05). In this low-HDL-C subgroup, patients with the D442G mutation had a significantly higher prevalence of vascular disease than those with no mutation (54.5% versus 24.4%; P &lt; 0.05), and an independent odds ratio of 4.9 (95% confidence interval, 1.05 to 22.65; P &lt; 0.05). In conclusion, the D442G mutation is an independent risk factor for atherosclerotic complications in dialysis patients with HDL-C levels below 45 mg/dl.
In Vitro Demonstration of Vascular Hyper-responsiveness in Experimental Hypertension
Authors: JOSEPH A. M. HINKE, Patricia A. Simpson
Journal: Circulation Research (1965)

The ventral caudal artery from DCA hypertensive and control rats was excised, mounted in a plastic chamber, and perfused with Krebs-Henseleit solution. Diameter of the artery and flow through the artery were measured at perfusion pressures ranging from 0 to 150 mm Hg. During these perfusions, constriction of the arterial segment was produced by adding norepinephrine, vasopressin, angiotensin II or rat serum in concentrations known to produce submaximal contractions. Samples of each experimental artery before and after artificial perfusion were fixed, sectioned, and stained. The tunica media of hypertensive arteries was thickened. Also, degenerative changes were observed in the internal elastic lamina and adjacent tunica media. Structural thickening of the tunica media was due primarily to expansion of the extracellular space and also due possibly to muscle fibre hypertrophy. In the absence of contraction, flow through the hypertensive artery was moderately reduced at all pressures because its lumen was narrowed by the thickened wall. Total wall tension, muscle tension, and elastic tension of the artery were estimated from the pressure-flow-radius data. Strength of muscular contraction was then measured in terms of work performed during contraction at a constant pressure. From this analysis, the muscle fibres in hypertensive arteries were found to be unequivocally hyper-responsive to norepinephrine, vasopressin, and rat serum. The possible cause of this hyper-responsive property is discussed. Serum was collected both from normotensive and from hypertensive donor rats and its pressor activity tested on the in vitro preparation. The pressor activity in hypertensive serum was found to be significantly elevated. The elasticity of the hypertensive artery was increased in the absence of contraction and unchanged during contraction. No hypertensive artery was found to be stiffer than normotensive arteries. These changes are probably related to degeneration of elastin.
Significant Variations in Elastometry Measurements Made Within Short-term in Patients With Chronic Liver Diseases
Authors: Fabio Nascimbeni, Pascal Lebray, Larysa Fedchuk, Claudia P Oliveira, Mario Reis Alvares-da-Silva, Anne Varault, Patrick Ingiliz, Yen Ngo, Mercedes de Torres, Mona Munteanu, Thierry Poynard, Vlad Ratziu
Journal: Clinical Gastroenterology and Hepatology (2014)
Human periostin gene expression in normal tissues, tumors and melanoma: evidences for periostin production by both stromal and melanoma cells
Authors: Gaëlle Tilman, Marina Mattiussi, Francis Brasseur, Nicolas van Baren, Anabelle Decottignies
Journal: Molecular Cancer (2007)

Abstract Background Recently, periostin ( POSTN ), a gene encoding a protein with similarity to the fasciclin family and involved in cell survival and angiogenesis, has emerged as a promising marker for tumor progression in various types of human cancers. There is some controversy regarding both POSTN expression levels and the nature of periostin-producing cells within tumors. In this study, we used quantitative RT-PCR to assess periostin gene expression in normal tissues, primary cell cultures, tumor tissues and tumor cell lines. Results Periostin expression levels are highly variable in both normal tissues and tumors and strong POSTN overexpression is mostly detected in tumors from pancreas and liver. POSTN is not expressed in blood cancers. In melanoma samples, average periostin expression is not increased in primary tumors whereas POSTN overexpression was detected in about 60% of melanoma metastatic tumors in the liver or lymph nodes. Identification of the cellular source of periostin production in melanoma metastases -cancer cells or stroma- was assessed by comparing periostin expression in 23 newly-established melanoma cell lines and matched tumors. In contrast to the reduction by more than 99% of COL6A3 stromal marker mRNA in all cell lines, significant POSTN transcription was maintained in some melanoma cell lines, suggesting that both stromal cells and melanoma cells express periostin. The high level of periostin expression in primary cultures of skin fibroblasts suggests that fibroblasts may contribute for a large part to periostin production in melanoma-associated stroma. On the other hand, periostin expression in melanoma cells is probably acquired during the tumorigenic process as 1) normal melanocytes do not express POSTN and 2) melanoma cells from distinct metastases of the same patient were associated with very different levels of periostin expression. Conclusion Our comparative analysis suggests that, although periostin overexpression is clearly detected in some cancers, it is not a general feature of tumors. In melanoma, our study identifies both stromal and melanoma cells as sources of periostin production and correlates POSTN expression levels with increased primary tumor thickness and metastatic process development.
JNK1/c-fos inhibits cardiomyocyte TNF- expression via a negative crosstalk with ERK and p38 MAPK in endotoxaemia
Authors: T. Peng, T. Zhang, X. Lu, Q. Feng
Journal: Cardiovascular Research (2008)

Myocardial tumour necrosis factor-alpha (TNF-alpha) production plays an important role in cardiac dysfunction during sepsis. The aim of this study was to investigate the role of c-Jun NH2-terminal kinases (JNK) signalling in cardiomyocyte TNF-alpha expression during lipopolysaccharide (LPS) stimulation and myocardial function in endotoxaemic mice.In cultured neonatal mouse cardiomyocytes, deficiency of JNK1 or selective inhibition of JNK1 signalling by over-expression of a dominant negative mutant of JNK1 enhanced LPS-induced TNF-alpha expression, which was associated with elevations in phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK). At the organ level, LPS-induced TNF-alpha expression was significantly increased in JNK1(-/-) compared with wild-type hearts. JNK1 activation by LPS also induced immediate c-fos expression in cardiomyocytes, which was blocked by inhibition of JNK1 signalling. The role of c-fos expression in LPS-induced TNF-alpha expression was investigated in both cultured c-fos(-/-) cardiomyocytes and isolated c-fos(-/-) hearts. Deficiency of c-fos significantly enhanced LPS-induced TNF-alpha expression in cardiomyocytes and isolated hearts. Over-expression of c-fos decreased TNF-alpha expression in LPS-stimulated cardiomyocytes, which was associated with a decrease in phosphorylation of ERK1/2 and p38. In mice with endotoxaemia, deficiency of either JNK1 or c-fos further decreased cardiac function compared with corresponding wild-type controls.JNK1/c-fos inhibits ERK1/2 and p38 MAPK signalling, leading to decreased cardiomyocyte TNF-alpha expression and improvements in cardiac function during endotoxaemia.
TNF-alpha, IL-1 and IL-6 concentration in bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer (NSCLC)
Authors: Marina Petrovic, Ivan Cekerevac, Vojislav Cupurdija, Vladimir Zdravkovic, Rada Vucic
Journal: European Respiratory Journal (2013)

AIM: Fiberoptic bronchoscopy and bronchoalveolar lavage (BAL) provide facilities for biologically active substances directly produced by the tumor. In the present study we have investigated the concentration of the following cytokines: TNF-alpha, IL-2 and IL-6 in bronchoalveolar lavage fluid (BALF) of non-small cell lung cancer. METHODS: The study group consisted of 30 patients with NSCLC. The control group consisted of 24 patients with non-malignant lung disease.All patients underwent bronchoscopy followed by bronchoalveolar lavage (BAL). RESULTS: The mean TNF-alpha concentration in Gr. I was 1258 pg/ml/mg p. and was significantly higher than in sarcoidosis (8.9 pg/ml/ mg p.) and COPD (0.75 pg/ml/mg p.). We observed a correlation between TNF-alpha concentration and the stage of malignant disease. The highest concentration was in IIIb stage (2965 pg/ml/mg p.). IL-6 concentration in malignant patients was strongly correlated with TNF-alpha concentration and was significantly higher than in control (291.58 pg/ml/mg p. in cancer patients, in sarcoidosis: 31.56 pg/ml/mg p. and in COPD: 49.94 pg/ml/mg p.). It was the highest in stage IV (432 pg/ml/mg p.). IL-1 concentrations were not significantly higher in malignant patients (45.32 pg/ml/mg p., nor in IIIa stage (48.24) pg/ml/mg p. as compared with controls (26.64 pg/ml/mg p. in sarcoidosis and 34.52 pg/ml/mg p. in COPD). CONCLUSION: TNF-alpha and IL6 in BALF might be used as a marker for NSCLC. TNF-alpha and IL6 level might be an indicator for the stage of NSCLC.
Regulation of Intracellular and Mitochondrial Sodium in Health and Disease
Authors: Elizabeth Murphy, David A. Eisner
Journal: Circulation Research (2009)

The transmembrane sodium gradient is essential for both excitability of the cardiac cell and the regulation of the cytoplasmic concentrations of Ca and protons. In addition, movements of Na across the mitochondrial membrane affect matrix protons and calcium. In the first part of the review, we discuss the most important pathways responsible for sarcolemmal and mitochondrial sodium movements. The bulk of the review considers the changes of intracellular Na concentration ([Na(+)](i)) that occur in disease, specifically, ischemia, reperfusion, and heart failure. We review evidence implicating the increase of intracellular sodium to either increased influx of sodium (via either sodium channels or sodium/hydrogen exchange) or, alternatively, to decreased efflux on the Na/K pump. Although much has been learned about sodium regulation in the heart, there are still many unanswered questions, particularly concerning mitochondrial Na regulation.