tbuckley/cabot-search huggingface dataset:
Abstract 2890: Mechanistic evaluation of the anti-tumor activities of 2-fluorofucose alone and in combination with anti-idiotype vaccination
Authors: Nicole M. Okeley, Weiping Zeng, Matthew R. Levengood, Julie A. McEarchern, Mechthild Jonas, Steven Duniho, Peter D. Senter, Che L. Law
Journal: Cancer Research (2014)

Abstract Fucose is a sugar that is widely incorporated in cellular glycoconjugates and has been implicated for roles in tumor progression and metastasis. An analog of fucose, 2-fluorofucose, has been shown to have activity in vitro and in vivo as an inhibitor of glycoconjugate fucosylation and has shown promising antitumor activity in cancer growth models as well as potentiation of the protective effect of a mouse B cell lymphoma idiotype vaccine against challenge by live A20 lymphoma cells (Okeley N.M. et al, PNAS 110, 5404-5409, 2013). The effects of 2-fluorofucose that mediate these activities was explored in vitro and in vivo. In vitro, we found that 2-fluorofucose is rapidly converted to GDP-2-fluorofucose, the active species that inhibits the de novo pathway for fucosylation of protein glycans. The molecule accumulates within cancer cells, and is retained with a half-life in the range of 20 hours. In vivo, evaluation of the effect of 2-fluorofucose treatment on the fucosylation and proliferation state of xenografts showed reduced LCA lectin binding by western blot and IHC, and reduced Ki-67 staining, suggesting a lower mitotic index in these tumors. Adoptive transfer experiments were undertaken in order to shed light onto potential mechanisms for the antitumor effects of 2-fluorofucose when used in a cancer vaccine setting. These studies were performed in mice that were immunized with an A20 idiotype vaccine in the presence or absence of 2-fluorofucose, prior to tumor challenge. The antitumor effects obtained when serum from 2-fluorofucose treated animals was injected into non-vaccinated mice suggested a role for defucosylated antibodies with enhanced ADCC activities. In addition, T cell depletion studies demonstrated that 2-fluorofucose stimulated a CD4+ T cell involvement in in the protection against tumor engraftment. These results suggest multifactorial roles for the activities of 2-fluorofucose as an anticancer agent and as a stimulator of vaccine activity. Citation Format: Nicole M. Okeley, Weiping Zeng, Matthew R. Levengood, Julie A. McEarchern, Mechthild Jonas, Steven Duniho, Peter D. Senter, Che L. Law. Mechanistic evaluation of the anti-tumor activities of 2-fluorofucose alone and in combination with anti-idiotype vaccination. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2890. doi:10.1158/1538-7445.AM2014-2890
ExpressionPlot: a web-based framework for analysis of RNA-Seq and microarray gene expression data
Authors: Brad A Friedman, Tom Maniatis
Journal: Genome biology (2011)

RNA-Seq and microarray platforms have emerged as important tools for detecting changes in gene expression and RNA processing in biological samples. We present ExpressionPlot, a software package consisting of a default back end, which prepares raw sequencing or Affymetrix microarray data, and a web-based front end, which offers a biologically centered interface to browse, visualize, and compare different data sets. Download and installation instructions, a user's manual, discussion group, and a prototype are available at https://doi.org/expressionplot.com/ .
Embryonic Epinephrine Synthesis in the Rat Heart Before Innervation
Authors: Steven N. Ebert, Robert P. Thompson
Journal: Circulation Research (2001)

Abstract —Epinephrine is a potent neurotransmitter and hormone that can influence cardiac performance beginning shortly after the first myocardial contractions occur in developing vertebrate embryos. In the present study, we provide evidence that the heart itself may produce epinephrine during embryonic development. Using antibodies that selectively recognize the catecholamine biosynthetic enzymes, tyrosine hydroxylase, dopamine β-hydroxylase, and phenylethanolamine N-methyltransferase, we used coimmunofluorescent staining techniques to identify cardiac cells that have the capability of producing catecholamines. Initially, cells expressing catecholamine biosynthetic enzymes were found interspersed throughout the myocardium, but by embryonic day 11.5 (E11.5), they became preferentially localized to the dorsal venous valve and atrioventricular canal regions. As development proceeded, catecholamine biosynthetic enzyme expression decreased in these regions but became quite strong along the crest of the interventricular septum by E16.5. This expression pattern was also transient, decreasing in the ventricular septum by E19.5. These data are consistent with a transient and progressive association of catecholamine-producing cells within regions of the heart that become the sinoatrial node, atrioventricular node, and bundle of His. This is the first evidence demonstrating that intrinsic cardiac adrenergic cells may be preferentially associated with early pacemaking and conduction tissue development.
New Mexican Hispanic Smokers Have Lower Odds of Chronic Obstructive Pulmonary Disease and Less Decline in Lung Function Than Non-Hispanic Whites
Authors: Shannon Bruse, Akshay Sood, Hans Petersen, Yushi Liu, Shuguang Leng, Juan C. Celedón, Frank Gilliland, Bartolomé Celli, Steven A. Belinsky, Yohannes Tesfaigzi
Journal: American Journal of Respiratory and Critical Care Medicine (2011)

Rationale: The epidemiology of cigarette smoking–related chronic obstructive pulmonary disease (COPD) is not well characterized in Hispanics in the United States. Understanding how ethnicity influences COPD is important for a number of reasons, from informing public health policies to dissecting the genetic and environmental effects that contribute to disease.Objectives: The present study assessed differences in risk between Hispanics and non-Hispanic whites for longitudinal and cross-sectional COPD phenotypes. Genetic ancestry was used to verify findings based on self-reported ethnicity. Hispanics in New Mexico are primarily differentiated from non-Hispanic whites by their proportion of Native American ancestry.Methods: The study was performed in a New Mexican cohort of current and former smokers. Self-reported Hispanic and non-Hispanic white ethnicity was validated by defining genetic ancestry proportions at the individual level using 48 single-nucleotide polymorphism markers. Self-reported ethnicity and genetic ancestry were independently used to assess associations with cross-sectional and longitudinal measures of lung function. Multivariable models were adjusted for indicators of smoking behavior.Measurements and Main Results: Self-reported Hispanic ethnicity was significantly associated with lower odds of COPD (odds ratio, 0.49; 95% confidence interval, 0.35–0.71; P = 0.007), and this protection was validated by the observation that Hispanic smokers have reduced risk of rapid decline in lung function (odds ratio, 0.48; 95% confidence interval, 0.30–0.78; P = 0.003). Similar findings were noted when Native American genetic ancestry proportions were used as predictors instead of self-report of Hispanic ethnicity.Conclusions: Hispanic ethnicity is inversely associated with cross-sectional and longitudinal spirometric COPD phenotypes even after adjustment for smoking. Native American genetic ancestry may account for this "Hispanic protection."
Insulin resistance in liver cirrhosis. Positron-emission tomography scan analysis of skeletal muscle glucose metabolism.
Authors: O Selberg, W Burchert, J vd Hoff, G J Meyer, H Hundeshagen, E Radoch, H J Balks, M J Müller
Journal: Journal of Clinical Investigation (1993)

Insulin resistance and glucose intolerance are a major feature of patients with liver cirrhosis. However, site and mechanism of insulin resistance in cirrhosis are unknown. We investigated insulin-induced glucose metabolism of skeletal muscle by positron-emission tomography to identify possible defects of muscle glucose metabolism in these patients.Whole body glucose disposal and oxidation were determined by the combined use of the euglycemic-hyperinsulinemic clamp technique (insulin infusion rate: 1 mU/kg body wt per min) and indirect calorimetry in seven patients with biopsy-proven liver cirrhosis (Child: 1A, 5B, and 1C) and five healthy volunteers. Muscle glucose uptake of the thighs was measured simultaneously by dynamic [18F]fluorodeoxyglucose positron-emission tomography scan.Both whole body and nonoxidative glucose disposal were significantly reduced in patients with liver cirrhosis (by 48%, P < 0.001, and 79%, P < 0.0001, respectively), whereas glucose oxidation and the increase in plasma lactate were normal. Concomitantly, skeletal muscle glucose uptake was reduced by 69% in liver cirrhosis (P < 0.003) and explained 55 or 92% of whole body glucose disposal in cirrhotics and controls, respectively. Analysis of kinetic constants using a three-compartment model further indicated reduced glucose transport (P < 0.05) but unchanged phosphorylation of glucose in patients with liver cirrhosis.Patients with liver cirrhosis show significant insulin resistance that is characterized by both decreased glucose transport and decreased nonoxidative glucose metabolism in skeletal muscle.
Extent and Cost of Informal Caregiving for Older Americans With Symptoms of Depression
Authors: Kenneth M Langa, Marcia A Valenstein, A Mark Fendrick, Mohammed U Kabeto, Sandeep Vijan
Journal: American Journal of Psychiatry (2004)

The purpose of this study was to obtain nationally representative estimates of the additional time and cost associated with informal caregiving for older Americans with depressive symptoms.Data from the 1993 Asset and Health Dynamics Among the Oldest Old Study, a nationally representative survey of people age 70 years or older (N=6,649), were used to determine the weekly hours and imputed costs of informal caregiving for elderly people with no depressive symptoms in the last week, one to three depressive symptoms in the last week, and four to eight depressive symptoms in the last week.Forty-four percent of survey respondents reported one to three depressive symptoms, and 18% reported four to eight depressive symptoms. In multivariate regression analyses that adjusted for sociodemographics, caregiver network, and coexisting chronic health conditions, respondents with no depressive symptoms received an average of 2.9 hours per week of informal care, compared with 4.3 hours per week for those with one to three symptoms and 6.0 hours per week for those with four to eight symptoms. Caregiving associated with depressive symptoms in elderly Americans represented a yearly cost of about $9 billion.Depressive symptoms in elderly persons are independently associated with significantly higher levels of informal caregiving, even after the effects of major coexisting chronic conditions are adjusted. The additional hours of care attributable to depressive symptoms represent a significant time commitment for family members and, therefore, a significant societal economic cost. Further research should evaluate the causal pathways by which depressive symptoms lead to high levels of caregiving and should examine whether successful treatment of depression reduces the need for informal care.
Epigenetic Regulation of c-ROS Receptor Tyrosine Kinase Expression in Malignant Gliomas
Authors: Hyun Jung Jun, Steve Woolfenden, Shanie Coven, Keara Lane, Roderick Bronson, David Housman, Alan Charest
Journal: Cancer Research (2009)

The proto-oncogene tyrosine kinase c-ROS is an orphan receptor whose normal expression pattern is tightly spatio-temporally restricted during development. In glioma, c-ROS mRNA expression is frequently ectopically up-regulated. In this study, we determined by immunohistochemical means that c-ROS receptor protein is present in 25% of low-grade and 30% of malignant glioma tumor samples from tissue microarrays. We then explored the molecular basis for the up-regulation of c-ROS expression in these tumors. We identified and characterized the c-ROS gene promoter region and report that the ectopic expression of c-ROS in tumors is tied to hypomethylation of a CpG island in the c-ROS promoter. Bisulfite sequencing analysis in glioma tumor samples revealed that demethylation of the CpG island (-384 to -132 bp) correlated with c-ROS expression. Moreover, c-ROS expression could be activated by treatment of c-ROS-negative cells with the demethylating agent 5-aza-2'-deoxycytidine. These results establish a strong link between c-ROS promoter demethylation and gain of c-ROS expression and function in glioma. Our data suggest that epigenetic activation of c-ROS represents an important oncogenic mechanism for glioma initiation and progression and suggest that cautionary measures in the clinical use of 5-aza-dC for the treatment of glioma be taken into consideration. [Cancer Res 2009;69(6):2180-4].
Hemagglutination and immunofluorescence studies on polymerized human serum albumin binding activity in chronic hepatitis B virus infection
Authors: Ignacio Mora, Juan Carlos Porres, Carlos Hernández Guio, Julia Gutiez, Vicente Carreño
Journal: Hepatology (1986)

The binding activity of polymerized human serum albumin was determined in 202 HBsAg carriers. The presence of polymerized human serum albumin receptor sites was tested by hemagglutination and differentiated from antihuman albumin antibodies by immunofluorescence, isolation of IgG and IgM fractions and testing of HBsAg anti–HBs immune complexes. A granular pattern with anti–HBs was specific for polymerized human serum albumin receptor sites as demonstrated with purified HBsAg. In addition, a linear pattern with fluoresceinated antihuman immunoglobulins might suggest the presence ofantihuman albumin antibodies (which was generally due to an IgG antibody). However, a granular pattern with fluoresceinated antihuman immunoglobulins may indicate the presence of HBsAg anti–HBs immune complexes. A weak linear pattern was also observed simultaneously in these cases, probably due to IgM antihuman albumin antibodies or an antipolymerized human serum albumin receptor site antibody. Of 202 HBsAg–positive patients, 71 showed polymerized human serum albumin receptor sites activity. The highest percentage of polymerized human serum albumin receptor sites was found among patients showing HBeAg and hepatitis B virus DNA polymerase positivity (96%), followed by HBeAg positivity and hepatitis B virus DNA polymerase negativity (48%), and anti–HBe positivity and hepatitis B virus DNA polymerase negativity (17%). In addition, a significant correlation between polymerized human serum albumin titers and hepatitis B virus DNA polymerase was found (r = 0.573, p &lt;0.01). However, at a similar HBeAg titer, patients who were positive for hepatitis B virus DNA polymerase had a higher polymerized human serum albumin receptor sites titer than those who were negative for hepatitis B virus DNA polymerase. The presence of a granular pattern with anti–HBs or fluoresceinated antihuman immunoglobulins means a positivity to polymerized human serum albumin receptor sites or the presence of HBsAg anti–HBs immune complexes, respectively. Furthermore, polymerized human serum albumin receptor sites titers correlate with hepatitis B virus DNA polymerase concentrations and may serve as indicators of viral replication.
Purifying Selection Detected in the Plastid Gene matK and Flanking Ribozyme Regions Within a Group II Intron of Nonphotosynthetic Plants
Authors: Nelson D. Young, Claude W. dePamphilis
Journal: Molecular Biology and Evolution (2000)

In a striking contrast, matK is one of the most rapidly evolving plastid genes and also one of the few plastid genes to be retained in all nonphotosynthetic plants examined to date. DNA sequences of this region were obtained from photosynthetic and nonphotosynthetic plants of Orobanchaceae and their relatives. The resulting plastid DNA phylogeny was congruent with that recently obtained from analyses of rps2 and provided much better resolution. This phylogeny was then used to examine the relative degrees of evolutionary constraint of both the matK gene and the non–protein-coding regions that flank it inside the trnK intron. The method of subtree contrasts was introduced to compare levels of constraint. matK has evolved with a low but significant level of constraint on its amino acid sequence in both photosynthetic and nonphotosynthetic plants. Constraint is greater in photosynthetic than in nonphotosynthetic plants of this group. Domain X, thought to contain the active site of the protein, is not significantly more constrained than the rest of the protein. The portions of the flanking regions that are thought to form paired stem structures also show constraint, but in this case, there is no significant difference in degree of constraint between photosynthetic and nonphotosynthetic plants.
A multimarker model to predict outcome in tamoxifen-treated breast cancer patients.
Authors: Steven P Linke, Troy M Bremer, Christopher D Herold, Guido Sauter, Cornelius Diamond
Journal: Clinical Cancer Research (2006)

Abstract PURPOSE: This study was designed to produce a model to predict outcome in tamoxifen-treated breast cancer patients based on clinicopathologic features and multiple molecular markers. EXPERIMENTAL DESIGN: This was a retrospective study of 324 stage I to III female breast cancer patients treated with tamoxifen for whom standard clinicopathologic data and tumor tissue microarrays were available. Nine molecular markers were studied by semiquantitative immunohistochemistry and/or fluorescence in situ hybridization. Cox proportional hazards analysis was used to determine the contributions of each variable to disease-specific and overall survival, and machine learning was used to produce a model to predict patient outcome. RESULTS: On a univariate basis, the following features were significantly associated with worse survival: high pathologic tumor or nodal class, histologic grade, epidermal growth factor receptor, ERBB2, MYC, or TP53; absent estrogen receptor (ER) or progesterone receptor; and low BCL2. CCND1 and CDKN1B did not reach statistical significance. On a multivariate basis, nodal class, ER, and MYC were statistically significant as independent factors for survival. However, the benefit of ER-positive status was moderated by BCL2, ERBB2, and progesterone receptor. BCL2 and TP53 also interacted as an independent risk factor. A kernel partial least squares polynomial model was developed with an area under the receiver operating characteristic curve of 0.90. CONCLUSIONS: Our data show the predictive value of BCL2, ERBB2, MYC, and TP53 in addition to the standard hormone receptors and clinicopathologic features, and they show the importance of conditional interpretation of certain molecular markers. Our multimarker predictive model performed significantly better than standard guidelines.
A transcriptome map of cellular transformation by the fos oncogene
Authors: Jared M Ordway, Steven D Fenster, Hong Ruan, Thomas Curran
Journal: Molecular Cancer (2005)

Abstract Background The c- fos gene was originally identified as the cellular homolog of the oncogene v- fos carried by the Finkel-Biskis-Jenkins and Finkel-Biskis-Reilly murine osteogenic sarcoma retroviruses. Sustained expression of fos is sufficient to induce cellular transformation in vitro and tumorigenesis in vivo . Fos functions as a component of the AP-1 transcription factor complex to regulate gene transcription and several differentially expressed genes have been identified in cells transformed by fos . We have extended these studies by constructing a cellular system for conditional transformation by v- fos . Using Affymetrix-based DNA microarray technology, we analyzed transcriptional changes over the course of transformation and reversion in an inducible v-fos system. Results Microarray analyses of temporal gene expression during the process of v-fos mediated cellular transformation and morphological reversion revealed a remarkably dynamic transcriptome. Of the more than 8000 genes analyzed in this study, 3766 genes were categorized into 18 gene-expression patterns by using self-organizing map analysis. By combining the analysis of gene expression profiles in stably transformed cells with the analysis of sequential expression patterns during conditional transformation, we identified a relatively small cohort of genes implicated in v-fos mediated cellular transformation. Conclusion This approach defines a general conditional cell transformation system that can be used to study the endogenous transcription regulatory mechanisms involved in transformation and tumorigenesis. In addition, this study is the first reported analysis of dynamic changes in gene expression throughout experimentally controlled morphological transformation mediated by v- fos .
Immunological studies in patients with Crohn's disease.
Authors: B R MacPherson, R J Albertini, W L Beeken
Journal: Gut (1976)

An investigation of immunological parameters was conducted in 38 patients with Crohn9s disease. The immunological tests employed included skin tests with dinitrochlorobenzene and a battery of common skin test antigens, lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen, serum immunoglobulins, and absolute lymphocyte counts. Crohn9s disease patients were divided into two groups, those treated with immunosuppressive drugs and those not receiving immunosuppressive medications. The latter group was subdivided into patients with active and inactive disease. Immunosuppressed patients with Crohn9s disease did not develop sensitivity to dinitrochlorobenzene and had mildly depressed skin test reactivity to common skin test procedures. Non-immunosuppressed patients with active Crohn9s disease also reacted less frequently to common skin test antigens, but 16 of 17 such patients developed sensitivity to dinitrochlorobenzene. Lymphocyte transformation with phytohaemagglutinin and pokeweed mitogen was normal in all groups of patients with Crohn9s disease. However, when suboptimal incubation periods were used with phytohaemagglutinin stimulation, there was a significant difference between Crohn9s disease patients and controls. Serum immunoglobulin levels and absolute lymphocyte counts were normal in all Crohn9s disease patients. We conclude that immunity in Crohn9s disease is qualitatively normal.
Asthma and the elite athlete: Summary of the International Olympic Committee's Consensus Conference, Lausanne, Switzerland, January 22-24, 2008
Authors: Kenneth D. Fitch, Malcolm Sue-Chu, Sandra D. Anderson, Louis-Philippe Boulet, Robert J. Hancox, Donald C. McKenzie, Vibeke Backer, Kenneth W. Rundell, Juan M. Alonso, Pascale Kippelen, Joseph M. Cummiskey, Alain Garnier, Arne Ljungqvist
Journal: Journal of Allergy and Clinical Immunology (2008)