tbuckley/cabot-search huggingface dataset:
Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer
Authors: Hagen F. Kennecke, Caroline H. Speers, Catherine A. Ennis, Karen Gelmon, Ivo A. Olivotto, Malcolm Hayes
Journal: Journal of Clinical Oncology (2012)

Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described.Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected.Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor-positive, node-negative breast cancer.Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.
Regulation of capillary perfusion by small arterioles is spatially organized.
Authors: M D Frame, I H Sarelius
Journal: Circulation Research (1993)

To explore a mechanism for spatial recruitment of capillaries, this study determined whether the arterioles controlling capillary perfusion, which typically arise as sequential branches along a transverse arteriole, could respond differently from each other in situ in a spatially ordered way. Diameter changes were measured for these arterioles at a known location in the intact microvasculature in the cremaster muscle of anesthetized Golden hamsters (N = 67); each arteriole controls separate capillary groups. These arterioles all had the same concentration dependence to locally (by micropipette) applied norepinephrine (NE, 10(-9) to 10(-3) mol/L), and 10(-9) mol/L NE did not induce diameter changes when applied locally to individual vessels. However, 10(-9) mol/L NE added to the tissue superfusate, or 5% added superfusate oxygen (also locally subthreshold), each induced significant diameter changes (both constrictions and dilations), in different branches, that were presumably due to summation of individually subthreshold events that changed the prevailing conditions at the point of observation. These significant diameter changes were related to the maximal diameter or to initial tone of the branches, but these changes occurred in different ways for NE versus oxygen. With NE, the branch arterioles that constricted (versus dilated) were significantly larger (maximal diameter, 22.3 +/- 2.6 versus 15.9 +/- 2.1 microns) and had higher tone (fractional constriction, 0.53 +/- 0.05 versus 0.63 +/- 0.05); with oxygen, those that constricted were the same size as those that dilated (maximal diameter, 28.6 +/- 1.1 versus 30.5 +/- 2.7 microns), but constrictors had lower tone (fractional constriction, 0.49 +/- 0.04 versus 0.39 +/- 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)
Undiagnosed coeliac disease does not appear to be associated with unfavourable outcome of pregnancy
Authors: L Greco
Journal: Gut (2003)

<b>Background:</b> In a previous hospital based study, we suggested that undiagnosed coeliac disease has a prevalence, among pregnant women, of 1:80, and is a cause of unfavourable outcome of pregnancy. <b>Aims:</b> In order to confirm or dismiss this hypothesis, which has significant public health implications, we carried out a large population based study on a stratified sample from the whole Campania region. <b>Patients:</b> During the period of the study, 5345 women were admitted to the OBS-GYN wards regional network: 5055 (95%) were enrolled in the study. <b>Methods:</b> Antihuman IgA class antitissue transglutaminase (TGASE) antibodies were tested by an ELISA method. Endomysial antibodies (EMA) were investigated on thin sections of human cord blood by an immunofluorescence test. The HLA class II DQA1*0501/DQB1*02 and DQA1*0301/DQB1*0302 haplotypes were assessed using the Eurospital Eu-DQ kit. Duodenal biopsy was not considered feasible by the ethics committee for pregnant women near delivery. <b>Results:</b> Fifty one of 5055 patients had confirmed positive results. We added to these 12 women with known coeliac disease, giving a prevalence rate for coeliac disease of 1:80 (exactly the value observed during the first study). Comparing the 51 TGASE positive with 4997 negative women, we did not observe an excess risk of abortion, premature delivery, small birth weight, or intrauterine growth retardation. Anaemia was more frequent in cases than controls. <b>Conclusions:</b> Undiagnosed coeliac disease is frequent among pregnant women (&gt;1%) but is not associated with an unfavourable outcome of pregnancy.
Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction
Authors: Lukasz Szumowski, Prashanthan Sanders, Franciszek Walczak, Mélèze Hocini, Pierre Jaïs, Roman Kepski, Ewa Szufladowicz, Piotr Urbanek, Paweł Derejko, Robert Bodalski, Michel Haïssaguerre
Journal: Journal of the American College of Cardiology (2004)
Why Your New Cancer Biomarker May Never Work: Recurrent Patterns and Remarkable Diversity in Biomarker Failures
Authors: Scott E. Kern
Journal: Cancer Research (2012)

Abstract Less than 1% of published cancer biomarkers actually enter clinical practice. Although best practices for biomarker development are published, optimistic investigators may not appreciate the statistical near-certainty and diverse modes by which the other 99% (likely including your favorite new marker) do indeed fail. Here, patterns of failure were abstracted for classification from publications and an online database detailing marker failures. Failure patterns formed a hierarchical logical structure, or outline, of an emerging, deeply complex, and arguably fascinating science of biomarker failure. A new cancer biomarker under development is likely to have already encountered one or more of the following fatal features encountered by prior markers: lack of clinical significance, hidden structure in the source data, a technically inadequate assay, inappropriate statistical methods, unmanageable domination of the data by normal variation, implausibility, deficiencies in the studied population or in the investigator system, and its disproof or abandonment for cause by others. A greater recognition of the science of biomarker failure and its near-complete ubiquity is constructive and celebrates a seemingly perpetual richness of biologic, technical, and philosophical complexity, the full appreciation of which could improve the management of scarce research resources. Cancer Res; 72(23); 6097–101. ©2012 AACR.
QUANTITATIVE STUDIES OF BRUCELLA PRECIPITIN SYSTEMS
Authors: R. B. Pennell, I. F. Huddleson
Journal: The Journal of Experimental Medicine (1938)

Quantitative cross precipitation studies with goat antisera show the three endoantigens of the brucella to be serologically distinguishable. Although the endoantigens of Br. abortus and Br. suis are very similar, they do not react identically, permitting the serological distinction of the two organisms. These differences in cross precipitation may be used to identify an organism of the brucella group or to determine the organism responsible for a brucella antiserum.
Evaluation of Intravenous Immunoglobulin as an Agent to Lower Allosensitization and Improve Transplantation in Highly Sensitized Adult Patients with End-Stage Renal Disease
Authors: Stanley C Jordan, Dolly Tyan, Don Stablein, Matthew McIntosh, Steve Rose, Ashley Vo, Mieko Toyoda, Connie Davis, Ron Shapiro, Deborah Adey, Dawn Milliner, Ralph Graff, Robert Steiner, Gaetano Ciancio, Shobah Sahney, Jimmy Light
Journal: Journal of the American Society of Nephrology (2004)

Reported are the reduction of anti-HLA antibody levels and improvement of transplant rates by intravenous immunoglobulin (IVIG) in a randomized, double-blind, placebo-controlled clinical trial. Between 1997 and 2000, a total of 101 adult patients with ESRD who were highly sensitized to HLA antigens (panel reactive antibody [PRA] ≥50% monthly for 3 mo) enrolled onto an NIH-sponsored trial (IG02). Patients received IVIG or placebo. Subjects received IVIG 2 g/kg monthly for 4 mo or an equivalent volume of placebo with additional infusions at 12 and 24 mo after entry if not transplanted. If transplanted, additional infusions were given monthly for 4 mo. Baseline PRA levels were similar in both groups. However, IVIG significantly reduced PRA levels in study subjects compared with placebo. Sixteen IVIG patients (35%) and eight placebo patients (17%) were transplanted. Rejection episodes occurred in 9 of 17 IVIG and 1 of 10 placebo subjects. Seven graft failures occurred (four IVIG, three placebo) among adherent patients with similar 2-yr graft survival rates (80% IVIG, 75% placebo). With a median follow-up of 2 yr after transplant, the viable transplants functioned normally with a mean ± SEM serum creatinine of 1.68 ± 0.28 for IVIG <i>versus</i> 1.28 ± 0.13 mg/dl for placebo. Adverse events rates were similar in both groups. We conclude that IVIG is better than placebo in reducing anti-HLA antibody levels and improving transplantation rates in highly sensitized patients with ESRD. Transplant rates for highly sensitized patients with ESRD awaiting kidney transplants are improved with IVIG therapy.
Locating the causes of religious commitment
Authors: Harvey Whitehouse
Journal: Behavioral and Brain Sciences (2004)

Atran &amp; Norenzayan (A&amp;N) survey a substantial body of theory and evidence on which there is broad agreement in the cognitive science of religion. Some parts of their argument (for instance, concerning the causes of costly commitment to religious beliefs) are more speculative and remain a focus of lively debate and further research.
In Vitro Methods of Toxicity Evaluation
Authors: R G Tardiff
Journal: The Annual Review of Pharmacology and Toxicology (1978)

Toxicity testing has relied almost exclusively on the use of whole animal systems to describe pathologic consequences of chemical exposures, to elucidate mechanisms of action, and to ascertain hazards to human health. In the past decade, in vitro test systems have gained increasing popularity not only because of advantages in mecha­ nistic investigations but also because of pragmatic considerations such as lower costs and shorter durations of experimentation. The wide variety of in vitro test systems falls into four categories: (a) microorganism systems, (b) mammalian cell culture systems, (c) tissue preparations, and (d) organ cultures. Because of their complexity and extensive literature bases, only the first two areas are reviewed in this chapter. The latter two categories will be treated in a future volume.
Core promoter/pre-core mutations are associated with lamivudine-induced HBeAg loss in chronic hepatitis B with genotype C
Authors: Yasuhiro Asahina, Namiki Izumi, Masakatsu Uchihara, Osamu Noguchi, Yuki Nishimura, Kazunari Inoue, Ken Ueda, Kaoru Tsuchiya, Kosei Hamano, Jun Itakura, Shozo Miyake
Journal: Journal of Hepatology (2003)
Smaller Left Heschl’s Gyrus Volume in Patients With Schizotypal Personality Disorder
Authors: Chandlee C. Dickey, Robert W. McCarley, Martina M. Voglmaier, Melissa Frumin, Margaret A. Niznikiewicz, Yoshio Hirayasu, Stephanie Fraone, Larry J. Seidman, Martha E. Shenton
Journal: American Journal of Psychiatry (2002)

Individuals with schizophrenia spectrum disorders evince similar genetic, neurotransmitter, neuropsychological, electrophysiological, and structural abnormalities. Magnetic resonance imaging (MRI) studies have shown smaller gray matter volume in patients with schizotypal personality disorder than in matched comparison subjects in the left superior temporal gyrus, an area important for language processing. In a further exploration, the authors studied two components of the superior temporal gyrus: Heschl's gyrus and the planum temporale.MRI scans were acquired from 21 male, neuroleptic-naive subjects recruited from the community who met DSM-IV criteria for schizotypal personality disorder and 22 male comparison subjects similar in age. Eighteen of the 21 subjects with schizotypal personality disorder had additional comorbid, nonpsychotic diagnoses. The superior temporal gyrus was manually delineated on coronal images with subsequent identification of Heschl's gyrus and the planum temporale. Exploratory correlations between region of interest volumes and neuropsychological measures were also performed.Left Heschl's gyrus gray matter volume was 21% smaller in the schizotypal personality disorder subjects than in the comparison subjects, a difference that was not associated with the presence of comorbid axis I disorders. There were no between-group volume differences in right Heschl's gyrus or in the right or left planum temporale. Exploratory analyses also showed a correlation between poor logical memory and smaller left Heschl's gyrus volume.Smaller left Heschl's gyrus gray matter volume in subjects with schizotypal personality disorder may help to explain the previously reported abnormality in the left superior temporal gyrus and may be a vulnerability marker for schizophrenia spectrum disorders.
Defective development of thymocytes overexpressing the costimulatory molecule, heat-stable antigen.
Authors: M R Hough, F Takei, R K Humphries, R Kay
Journal: The Journal of Experimental Medicine (1994)

Heat-stable antigen (HSA) is a small, glycosyl phosphatidylinositol-anchored protein that can act as a costimulatory molecule for antigen-dependent activation of helper T cells. In addition to being expressed on antigen-presenting B cells, HSA is also expressed during the initial stages of T cell development in the thymus. HSA levels are very high on immature CD4-, CD8- double negative thymocytes, but are reduced on CD4+, CD8+ double positive cells undergoing selection in the thymus, and are entirely eliminated when these cells differentiate into immunologically competent CD4+ or CD8+ single positive T cells. To examine the potential roles of this molecule in T cell development and selection, we generated transgenic mice in which HSA was highly expressed on all classes of thymocytes. The consequence of deregulated HSA expression was a pronounced reduction in the numbers of double positive and single positive thymocytes, whereas the numbers of their double negative precursors were largely unaffected. These results demonstrate that downregulation of HSA expression at the double positive stage is a critical event in thymocyte development. The depletion of thymocytes resulting from HSA overexpression begins at the same time as the onset of negative selection, suggesting that HSA may provide signals that contribute to determining the efficiency of this process.
Epidermal Growth Factor–Induced Cyclooxygenase-2 Expression Is Mediated through Phosphatidylinositol-3 Kinase, Not Mitogen-Activated Protein/Extracellular Signal-Regulated Kinase Kinase, in Recurrent Respiratory Papillomas
Authors: Rong Wu, Allan L. Abramson, Mark J. Shikowitz, Andrew J. Dannenberg, Bettie M. Steinberg
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Recurrent respiratory papillomas, caused by human papillomaviruses, are premalignant tumors that overexpress the epidermal growth factor receptor (EGFR). The goals of this study were as follows: (a) to evaluate the expression of cyclooxygenase-2 (COX-2) in papillomas, (b) to investigate the role of EGFR signaling in COX-2 expression, and (c) to determine whether COX-2 activity is important for the growth of papilloma cells. Experimental Design: Immunohistochemistry, Western blotting, and real-time PCR were used to determine levels of COX-2 in papilloma and normal laryngeal tissue. Explant cultures of both normal laryngeal and papilloma cells were used to define the signaling pathways that regulate COX-2 expression and investigate the potential of targeting COX-2 as a strategy to suppress papilloma growth. Results: COX-2 levels were markedly increased in papillomas. In vitro studies suggested that overexpression in papillomas reflected activation of EGFR→phosphatidylinositol 3-kinase signaling. Treatment with prostaglandin E2 (PGE2) induced COX-2, whereas celecoxib, a selective COX-2 inhibitor, suppressed levels of COX-2, suggesting a positive feedback loop. Moreover, treatment with PGE2 stimulated papilloma cell growth, whereas celecoxib suppressed proliferation and induced apoptosis. Conclusions: Overexpression of COX-2 in papillomas seems to be a consequence of enhanced EGFR→phosphatidylinositol 3-kinase signaling. We propose a positive feedback loop for COX-2 expression, with induction of COX-2 resulting in enhanced PGE2 synthesis and further expression of COX-2 that contributes to the growth of papillomas in vivo. These data strengthen the rationale for evaluating whether nonsteroidal anti-inflammatory drugs, prototypic COX inhibitors, will be useful in the management of respiratory papillomas.
Enhancing the antihepatitis B virus immune response by adefovir dipivoxil and entecavir therapies
Authors: Yanfang Jiang, Wanyu Li, Lei Yu, Jingjing Liu, Guijie Xin, Hongqing Yan, Pinghui Sun, Hong Zhang, Damo Xu, Junqi Niu
Journal: Cellular and Molecular Immunology (2010)
Secondary antibody responses in vitro to L-glutamic acid60-L-alanine30-L-tyrosine10 (GAT) by (responder X nonresponder)F1 spleen cells stimulated by parental GAT-macrophages.
Authors: C W Pierce, R N Germain, J A Kapp, B Benacerraf
Journal: The Journal of Experimental Medicine (1977)

The development of IgG L-glutamic Acid60-L-alanine30-L-tyrosine10 (GAT)-specific plaque-forming cell responses in vitro by virgin and immune (responder X nonresponder)F1 spleen cells after stimulation with responder and nonresponder parental GAT-macrophages (Mphi) was investigated. Virgin F1 spleen cells developed comparable primary responses to both parental GAT-Mphi. By contrast, F1 spleen cells from mice immunized with GAT or responder parental GAT-Mphi developed secondary responses after stimulation with only responder parental GAT-Mphi. Spleen cells from F1 mice immunized with nonresponder parental GAT-Mphi developed secondary responses to these GAT-Mphi, but failed to respond to responder parental GAT-Mphi. These results are discussed in the context of genetic restrictions regulating Mphi-T-cell interactions in secondary antibody responses and the possible expression of Ir-gene function in Mphi.
ID helix-loop-helix proteins as determinants of cell survival in B-cell chronic lymphocytic leukemia cells in vitro
Authors: Sarah Weiler, Jolaolu A Ademokun, John D Norton
Journal: Molecular Cancer (2015)

Members of the inhibitor of DNA-binding (ID) family of helix-loop-helix proteins have been causally implicated in the pathogenesis of several types of B-cell lineage malignancy, either on the basis of mutation or by altered expression. B-cell chronic lymphocytic leukemia encompasses a heterogeneous group of disorders and is the commonest leukaemia type in the Western world. In this study, we have investigated the pathobiological functions of the ID2 and ID3 proteins in this disease with an emphasis on their role in regulating leukemic cell death/survival. Bioinformatics analysis of microarray gene expression data was used to investigate expression of ID2/ID3 in leukemic versus normal B cells, their association with clinical course of disease and molecular sub-type and to reconstruct a gene regulatory network using the 'maximum information coefficient' (MIC) for target gene inference. In vitro cultured primary leukemia cells, either in isolation or co-cultured with accessory vascular endothelial cells, were used to investigate ID2/ID3 protein expression by western blotting and to assess the cytotoxic response of different drugs (fludarabine, chlorambucil, ethacrynic acid) by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. ID2/ID3 protein levels in primary leukemia cells and in MEC1 cells were manipulated by transduction with siRNA reagents. Datamining showed that the expression profiles of ID2 and ID3 are associated with distinct pathobiological features of disease and implicated both genes in regulating cell death/survival by targeting multiple non-overlapping sets of apoptosis effecter genes. Consistent with microarray data, the overall pattern of ID2/ID3 protein expression in relation to cell death/survival responses of primary leukemia cells was suggestive of a pro-survival function for both ID proteins. This was confirmed by siRNA knock-down experiments in MEC1 cells and in primary leukemia cells, but with variability in the dependence of leukemic cells from different patients on ID protein expression for cell survival. Vascular endothelial cells rescued leukemia cells from spontaneous and cytotoxic drug-induced cell death at least in part, via an ID protein-coupled redox-dependent mechanism. Our study provides evidence for a pro-survival function of the ID2/ID3 proteins in chronic lymphocytic leukemia cells and also highlights these proteins as potential determinants of the pathobiology of this disorder.
Causes and Consequences of Variability in Peptide Mating Pheromones of Ascomycete Fungi
Authors: S. H. Martin, B. D. Wingfield, M. J. Wingfield, E. T. Steenkamp
Journal: Molecular Biology and Evolution (2011)

The reproductive genes of fungi, like those of many other organisms, are thought to diversify rapidly. This phenomenon could be associated with the formation of reproductive barriers and speciation. Ascomycetes produce two classes of mating type-specific peptide pheromones. These are required for recognition between the mating types of heterothallic species. Little is known regarding the diversity or the extent of species specificity in pheromone peptides among these fungi. We compared the putative protein-coding DNA sequences of the 2 pheromone classes from 70 species of Ascomycetes. The data set included previously described pheromones and putative pheromones identified from genomic sequences. In addition, pheromone genes from 12 Fusarium species in the Gibberella fujikuroi complex were amplified and sequenced. Pheromones were largely conserved among species in this complex and, therefore, cannot alone account for the reproductive barriers observed between these species. In contrast, pheromone peptides were highly diverse among many other Ascomycetes, with evidence for both positive diversifying selection and relaxed selective constraint. Repeats of the α-factor-like pheromone, which occur in tandem arrays of variable copy number, were found to be conserved through purifying selection and not concerted evolution. This implies that sequence specificity may be important for pheromone reception and that interspecific differences may indeed be associated with functional divergence. Our findings also suggest that frequent duplication and loss causes the tandem repeats to experience "birth-and-death" evolution, which could in fact facilitate interspecific divergence of pheromone peptide sequences.