tbuckley/cabot-search huggingface dataset:
678 DIAGNOSTIC AND CLINICAL APPLICATION OF A NEW LINE IMMUNOASSAY THAT SIMULTANEOUSLY DETECTS THE MULTIPLE NUCLEAR DOT SPECIFIC ANTIGENS IN PRIMARY BILIARY CIRRHOSIS
Authors: M. Mytilinaiou, W. Meyer, A. Janssen, P. Pavlides, C. Probst, N.K. Gatselis, L. Komorowski, W. Schlumberger, D. Vergani, D.P. Bogdanos
Journal: Journal of Hepatology (2009)
An MRI Study of Superior Temporal Gyrus Volume in Women With Schizotypal Personality Disorder
Authors: Chandlee C. Dickey, Robert W. McCarley, Martina M. Voglmaier, Margaret A. Niznikiewicz, Larry J. Seidman, Susan Demeo, Melissa Frumin, Martha E. Shenton
Journal: American Journal of Psychiatry (2003)

An abnormal superior temporal gyrus has figured prominently in schizophrenia research, and left superior temporal gyrus volume has been shown to be smaller in male subjects with schizotypal personality disorder. This is the first structural magnetic resonance imaging study to examine a group of female subjects with schizotypal personality disorder.The superior temporal gyrus was drawn on coronal images acquired from female subjects recruited from the community (schizotypal personality disorder group: N=21, comparison group: N=29).There were no gray matter volume differences in the left or right superior temporal gyrus between the subjects with schizotypal personality disorder and the comparison subjects. Within the schizotypal personality disorder group, however, there was an interaction between hemisphere and family history of mental illness. Moreover, subjects with schizotypal personality disorder did demonstrate formal thought disorder and a negative correlation between left superior temporal gyrus volume and odd speech.This study of female subjects with schizotypal personality disorder showed no superior temporal gyrus volume differences, but preliminary findings indicate that among female subjects with schizotypal personality disorder, there is a left-right difference in those who have a family history of mental illness relative to those who do not. These data also suggest an association between abnormal speech and left superior temporal gyrus volume, a finding similar to that found in schizophrenia. Results from this study thus clearly reinforce the importance of studying female subjects separately.
Intentional change, intrinsic motivations, and goal generation
Authors: Riccardo Manzotti, Paolo Moderato
Journal: Behavioral and Brain Sciences (2014)

Abstract Wilson et al. draw our attention to the problem of a science of intentional change. We stress the connection between their approach and existing paradigms for learning and goal generation that have been developed in machine learning, artificial intelligence, and psychology. These paradigms outline the structural principles of a domain-general and teleologically open agent.
IgA Nephropathy: Molecular Mechanisms of the Disease
Authors: Jiri Mestecky, Milan Raska, Bruce A. Julian, Ali G. Gharavi, Matthew B. Renfrow, Zina Moldoveanu, Lea Novak, Karel Matousovic, Jan Novak
Journal: Annual Review of Pathology Mechanisms of Disease (2012)

Studies of molecular and cellular interactions involved in the pathogenesis of IgA nephropathy have revealed the autoimmune nature of this most common primary glomerulonephritis. In patients with this disease, altered glycan structures in the unique hinge region of the heavy chains of IgA1 molecules lead to the exposure of antigenic determinants, which are recognized by naturally occurring antiglycan antibodies of the IgG and/or IgA1 isotype. As a result, nephritogenic immune complexes form in the circulation and deposit in the glomerular mesangium. Deposited immune complexes induce proliferation of resident mesangial cells, increased production of extracellular matrix proteins and cytokines, and ultimately loss of glomerular function. Structural elucidation of the nature of these immune complexes and their biological activity should provide a rational basis for an effective, immunologically mediated inhibition of the formation of nephritogenic immune complexes that could be used as a disease-specific therapeutic approach.
CIITA-Induced MHC Class II Expression in Mammary Adenocarcinoma Leads to a Th1 Polarization of the Tumor Microenvironment, Tumor Rejection, and Specific Antitumor Memory
Authors: Lorenzo Mortara, Patrizia Castellani, Raffaella Meazza, Giovanna Tosi, Andrea De Lerma Barbaro, Francesco A. Procopio, Alberto Comes, Luciano Zardi, Silvano Ferrini, Roberto S. Accolla
Journal: Clinical Cancer Research (2006)

Abstract Purpose: We have shown previously that the MHC class II–negative murine TS/A adenocarcinoma is rejected in vivo if induced to express MHC class II molecules by transfection of the MHC class II transactivator CIITA. In this study, we explored the immunologic basis of tumor rejection and the correlation between histopathology of tumor tissue and immune rejection. Experimental Design: Stable TS/A-CIITA transfectants were generated and injected into mice. In vivo cell depletion, immunohistochemistry of tumor tissues, and immune functional assays were done to assess the cellular and immunologic basis of rejection. Results: Ninety-two percent of mice injected with TS/A-CIITA rejected the tumor and were completely resistant to challenge with parental TS/A. Only CD4+ and CD8+ cells were required for rejection. The tumor microenvironment in TS/A-CIITA-injected mice changed dramatically when compared with the TS/A parental-injected mice. Rapid infiltration with CD4+ T cells followed by dendritic cells, CD8+ T cells, and granulocytes was observed. Importantly, TS/A-CIITA cells could act as antigen-presenting cells because they process and present nominal antigens to CD4+ T cells. Tumor-specific CD4+ T cells of TS/A-CIITA-injected mice had the functional characteristics of Th1 cells and produced IFN-γ and this was relevant for generation and maintenance of protective antitumor response, because IFN-γ knockout mice were no longer rejecting TS/A-CIITA tumor cells. Conclusion: CIITA-dependent MHC class II expression confers to TS/A tumor cells the capacity to act as a protective vaccine against the tumor by triggering tumor antigen presentation to T helper cells, antitumor polarization of cellular and soluble components of the tumor microenvironment, and establishment of antitumor immune memory.
Echinomycin, a Small-Molecule Inhibitor of Hypoxia-Inducible Factor-1 DNA-Binding Activity
Authors: Dehe Kong, Eun Jung Park, Andrew G. Stephen, Maura Calvani, John H. Cardellina, Anne Monks, Robert J. Fisher, Robert H. Shoemaker, Giovanni Melillo
Journal: Cancer Research (2005)

Abstract The identification of small molecules that inhibit the sequence-specific binding of transcription factors to DNA is an attractive approach for regulation of gene expression. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that controls genes involved in glycolysis, angiogenesis, migration, and invasion, all of which are important for tumor progression and metastasis. To identify inhibitors of HIF-1 DNA-binding activity, we expressed truncated HIF-1α and HIF-1β proteins containing the basic-helix-loop-helix and PAS domains. Expressed recombinant HIF-1α and HIF-1β proteins induced a specific DNA-binding activity to a double-stranded oligonucleotide containing a canonical hypoxia-responsive element (HRE). One hundred twenty-eight compounds previously identified in a HIF-1–targeted cell-based high-throughput screen of the National Cancer Institute 140,000 small-molecule library were tested in a 96-well plate ELISA for inhibition of HIF-1 DNA-binding activity. One of the most potent compounds identified, echinomycin (NSC-13502), a small-molecule known to bind DNA in a sequence-specific fashion, was further investigated. Electrophoretic mobility shift assay experiments showed that NSC-13502 inhibited binding of HIF-1α and HIF-1β proteins to a HRE sequence but not binding of the corresponding proteins to activator protein-1 (AP-1) or nuclear factor-κB (NF-κB) consensus sequences. Interestingly, chromatin immunoprecipitation experiments showed that NSC-13502 specifically inhibited binding of HIF-1 to the HRE sequence contained in the vascular endothelial growth factor (VEGF) promoter but not binding of AP-1 or NF-κB to promoter regions of corresponding target genes. Accordingly, NSC-13502 inhibited hypoxic induction of luciferase in U251-HRE cells and VEGF mRNA expression in U251 cells. Our results indicate that it is possible to identify small molecules that inhibit HIF-1 DNA binding to endogenous promoters.
Palisading cells of rheumatoid nodules: comparison with synovial intimal cells.
Authors: J C Edwards, L S Wilkinson, A A Pitsillides
Journal: Annals of the Rheumatic Diseases (1993)

OBJECTIVES--The palisading cells of rheumatoid nodules share certain features with synovial intimal cells. The similarities between the two cell populations have been reassessed using new cytochemical markers. METHODS--Cell populations in cryostat sections of non-inflamed, rheumatoid and osteoarthritic synovial tissues, and rheumatoid nodules were assessed for the presence of CD68, prolyl hydroxylase, vascular cell adhesion molecule 1 (VCAM-1), and the alpha 4 and beta 1 integrin chains, and the activity of uridine diphosphoglucose dehydrogenase (UDPGD) and nonspecific esterase. RESULTS--Synovial intimal cells formed a dual population of macrophages (nonspecific esterase positive, strongly positive for CD68) and fibroblastic cells (prolyl hydroxylase positive). The latter showed prominent VCAM-1 expression and high UDPGD activity as previously reported and also prominent beta 1 integrin chain expression. Palisading cells similarly proved to be a dual population of macrophages and fibroblastic cells. In contrast with synovial intima, however, the fibroblastic cells lacked UDPGD activity and expression of VCAM-1 and showed no preferential expression of the beta 1 integrin chain. The exception to this rule was where nodules contained central clefts, which were lined with cells showing all the features associated with synovial intimal cells. CONCLUSION--Palisading cells are a mixture of macrophages and fibroblasts, but the latter show no evidence of synoviocyte differentiation. Cells with features of synoviocytes may occur lining clefts within areas of necrobiosis.
Effects of steroid therapy on inflammatory cell subtypes in asthma
Authors: L. P. Boulet
Journal: Thorax (2010)

Asthma is a chronic condition that usually develops after environmental exposures in genetically predisposed individuals.1 It is considered an inflammatory disease leading to airway structural changes (remodelling), both of these processes being involved in the development of airway hyper-responsiveness (AHR) and variable airway obstruction.2 When inflammation and remodelling increase to a sufficient degree, symptomatic asthma occurs.3

Although asthma has been recognised for a very long time as a heterogeneous condition, recent efforts have been devoted to better characterising its various phenotypes.4 The term ‘phenotype’ refers to ‘a set of observable characteristics of an individual or group resulting from the interaction of its genotype with its environment’. Although these phenotypes may overlap or possibly vary over time, their characterisation may help to identify the predominant mechanisms involved and specific patterns of clinical presentation, predict clinical outcomes and may guide treatment. There is still, however, a lack of data in this field.

Various classification systems have been proposed for asthma phenotypes.4 Currently, these phenotypes are usually defined according to their inducers, physiological characteristics, clinical features or—particularly since the development of non-invasive measures of airway inflammation—by their inflammatory characteristics.5–7 The main categories of airway inflammatory phenotypes identified in subjects with asthma are the eosinophilic and non-eosinophilic types, with the latter including neutrophilic and paucigranulocytopenic subtypes. A mixed form also exists in which both eosinophils and neutrophils are increased. These inflammatory phenotypes can be observed in children as well as in adults.8 9

A frequently encountered phenotype of asthma is the eosinophilic type. It is associated with allergic or occupational asthma, steroid withdrawal, aspirin intolerance/nasal polyps and a subset of severe asthma.6 10–12 An increase in airway neutrophils has been observed in subgroups of individuals with occupational or severe asthma,11 13 14 smokers,15 16 …
Mitotic Index and Benefit of Adjuvant Anthracycline-Based Chemotherapy in Patients With Early Breast Cancer
Authors: Fabrice Andre, Ahmed Khalil, Khemaies Slimane, Christophe Massard, Marie Christine Mathieu, Stéphane Vignot, Hazem Assi, Suzette Delaloge, Marc Spielmann
Journal: Journal of Clinical Oncology (2005)

Purpose We have evaluated whether the mitotic index could predict the benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines. Patients and Methods A total of 937 patients from a single institution were included in two randomized trials that compared adjuvant anthracycline-based chemotherapy with no chemotherapy. These patients account for 83% of the overall population included in these trials. The first trial included premenopausal patients with node-negative disease, and the second one included postmenopausal patients, regardless of lymph node status. The treatment benefit was assessed according to the number of mitoses per field (×400). Results The mitotic index was assessable in 888 patients (94%). All the patients presented as either node-positive or an average-risk breast cancer according to 2003 Saint Gallen consensus conference guidelines. The 5-year overall survival rates were 91% and 87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients with low/medium mitotic index (&lt; three mitoses/field; n = 450), the 5-year overall survival rate was 95% for patients treated or not with adjuvant chemotherapy (P = .56). In patients with high mitotic index (≥ three mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for patients treated or not treated with adjuvant chemotherapy, respectively (P = .02). Conclusion A high mitotic index is associated with the efficacy of adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant chemotherapy in daily practice.
Lack of association between angiotensin converting enzyme gene polymorphism and Korean Behcet's disease
Authors: H K Chang
Journal: Annals of the Rheumatic Diseases (2003)

heumatoid arthritis (RA) is a chronic inflammatory disease which is characterised mainly by synovial inflammation and joint destruction, as well as extraarticular manifestations. 1 Cytokines have a central role in the pathogenesis of this synovial inflammation.Tumour necrosis factor a (TNFa) is one of the dominant cytokines.Many studies have shown that TNFa is present in biologically significant amounts in RA synovial tissue and fluids, and the amount seems to parallel the extent of inflammation and bone erosion. 2 3 Persistent inflamed monarthritis in patients with RA is difficult to treat.Usually it is treated with local patches, intraarticular injections of steroids, or even with chemical, radioactive, or surgical synovectomy. 4 The introduction of anti-TNFa treatments, especially the infusion of infliximab, 5 prompted us to investigate the effectiveness and safety of intra-articular injection of infliximab in patients with RA and resistant monarthritis.
Fibroblast Growth Factor Receptor 1 Promotes Proliferation and Survival via Activation of the Mitogen-Activated Protein Kinase Pathway in Bladder Cancer
Authors: Darren C. Tomlinson, Fiona R. Lamont, Steve D. Shnyder, Margaret A. Knowles
Journal: Cancer Research (2009)

Abstract Fibroblast growth factor receptors (FGFR) play key roles in proliferation, differentiation, and tumorigenesis. Many urothelial carcinomas contain activating point mutations or increased expression of FGFR3. However, little is known about the role of other FGFRs. We examined FGFR expression in telomerase-immortalized normal human urothelial cells, urothelial carcinoma cell lines, and tumor samples and showed that FGFR1 expression is increased in a high proportion of cell lines and tumors independent of stage and grade. To determine the role of FGFR1 in low-stage bladder cancer, we overexpressed FGFR1 in telomerase-immortalized normal human urothelial cells and examined changes in proliferation and cell survival in response to FGF2. FGFR1 stimulation increased proliferation and reduced apoptosis. To elucidate the mechanistic basis for these alterations, we examined the signaling cascades activated by FGFR1. FRS2α and PLCγ were activated in response to FGF2, leading to activation of the mitogen-activated protein kinase pathway. The level of mitogen-activated protein kinase activation correlated with the level of cyclin D1, MCL1, and phospho-BAD, which also correlated with FGFR-induced proliferation and survival. Knockdown of FGFR1 in urothelial carcinoma cell lines revealed differential FGFR1 dependence. JMSU1 cells were dependent on FGFR1 expression for survival but three other cell lines were not. Two cell lines (JMSU1 and UMUC3) were dependent on FGFR1 for growth in soft agar. Only one of the cell lines tested (UMUC3) was frankly tumorigenic; here, FGFR1 knockdown inhibited tumor growth. Our results indicate that FGFR1 has significant effects on urothelial cell phenotype and may represent a useful therapeutic target in some cases of urothelial carcinoma. [Cancer Res 2009;69(11):4613–20]
Cerebrovascular Disease Risk in Older Head and Neck Cancer Patients After Radiotherapy
Authors: Grace L. Smith, Benjamin D. Smith, Thomas A. Buchholz, Sharon H. Giordano, Adam S. Garden, Wendy A. Woodward, Harlan M. Krumholz, Randal S. Weber, K.-Kian Ang, David I. Rosenthal
Journal: Journal of Clinical Oncology (2008)

Cerebrovascular disease is common in head and neck cancer patients, but it is unknown whether radiotherapy increases the cerebrovascular disease risk in this population.We identified 6,862 patients (age > 65 years) from the Surveillance, Epidemiology, and End Results (SEER) -Medicare cohort diagnosed with nonmetastatic head and neck cancer between 1992 and 2002. Using proportional hazards regression, we compared risk of cerebrovascular events (stroke, carotid revascularization, or stroke death) after treatment with radiotherapy alone, surgery plus radiotherapy, or surgery alone. To further validate whether treatment groups had equivalent baseline risk of vascular disease, we compared the risks of developing a control diagnosis, cardiac events (myocardial infarction, percutaneous coronary intervention, coronary artery bypass graft, or cardiac death). Unlike cerebrovascular risk, no difference in cardiac risk was hypothesized.Mean age was 76 +/- 7 years. Ten-year incidence of cerebrovascular events was 34% in patients treated with radiotherapy alone compared with 25% in patients treated with surgery plus radiotherapy and 26% in patients treated with surgery alone (P < .001). After adjusting for covariates, patients treated with radiotherapy alone had increased cerebrovascular risk compared with surgery plus radiotherapy (hazard ratio [HR] = 1.42; 95% CI, 1.14 to 1.77) and surgery alone (HR = 1.50; 95% CI, 1.18 to 1.90). However, no difference was found for surgery plus radiotherapy versus surgery alone (P = .60). As expected, patients treated with radiotherapy alone had no increased cardiac risk compared with the other treatment groups (P = .63 and P = .81).Definitive radiotherapy for head and neck cancer, but not postoperative radiotherapy, was associated with excess cerebrovascular disease risk in older patients.
LEUKOKINETIC STUDIES. IV. THE TOTAL BLOOD, CIRCULATING AND MARGINAL GRANULOCYTE POOLS AND THE GRANULOCYTE TURNOVER RATE IN NORMAL SUBJECTS*
Authors: J. W. Athens, O. P. Haab, S. O. Raab, A. M. Mauer, H. Ashenbrucker, G. E. Cartwright, M. M. Wintrobe
Journal: Journal of Clinical Investigation (1961)
Nephrogenic Factors Promote Differentiation of Mouse Embryonic Stem Cells into Renal Epithelia
Authors: Doyeob Kim, Gregory R. Dressler
Journal: Journal of the American Society of Nephrology (2005)

Embryonic stem (ES) cells have been induced to differentiate <i>in vitro</i> into a broad spectrum of specialized cell types, including hematopoietic, pancreatic, and neuronal cell types. Such ES-derived cells can provide a valuable source of progenitor cell types. Whereas undifferentiated ES cells can become integrated into a developing kidney and contribute to tubular epithelia, the ability to generate renal precursor cells <i>in vitro</i> has not been reported. This study used a combination of nephrogenic growth factors to differentiate ES cells into renal epithelial cells that are capable of integrating into a developing kidney with very high efficiency. Using a combination of retinoic acid, Activin-A, and Bmp7, cultured ES cells can be induced to express markers specific for the intermediate mesoderm, from which the kidneys arise. Embryoid bodies that are cultured in the presence of nephrogenic factors can respond to inductive signals and form epithelial structures <i>in vitro</i>. When injected into developing kidney rudiments, treated ES cells contribute to tubular epithelia with near 100% efficiency. These methods may facilitate the large-scale culture of renal epithelial precursor cells for a variety of applications.
HERPES-VIRUS IMMUNITY AND ACUTE GRAFT-VERSUS-HOST DISEASE
Authors: J.W. Gratama, T. Stijnen, H.T. Weiland, A.C. Hekker, G.C. De Gast, F.E. Zwaan, T.F. Weijers, J. D'Amaro, T.H. The, J.M.J.J. Vossen
Journal: The Lancet (1987)
The search for fixed generalizable limits of “pure STM” capacity: Problems with theoretical proposals based on independent chunks
Authors: K. Anders Ericsson, Elizabeth P. Kirk
Journal: Behavioral and Brain Sciences (2001)

Cowan's experimental techniques cannot constrain subject's recall of presented information to distinct independent chunks in short-term memory (STM). The encoding of associations in long-term memory contaminates recall of pure STM capacity. Even in task environments where the functional independence of chunks is convincingly demonstrated, individuals can increase the storage of independent chunks with deliberate practice – well above the magical number four.
Gastric acid secretion and risk of recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage
Authors: O. Kronborg
Journal: Gut (1974)

The value of insulin and augmented histamine tests in predicting recurrence of duodenal ulcer within six to eight years after truncal vagotomy and drainage was assessed in a series of 500 consecutively and electively operated patients. Criteria of recurrence were established by a discriminative analysis of gastric acid secretion parameters. Recurrence was predicted with a probability of about 75% in patients with dyspepsia, the proportion between recurrences and dyspeptic nonrecurrences being 1:1. The discriminatory ability of the insulin test was no better than that of the postoperative histamine test. Men with a preoperative PAO > 46.1 m-equiv/h had a risk of recurrence of 21%, women with a PAO > 41.5 m-equiv/h, 28%. Below these levels the risk was 5 and 1% respectively, demonstrating that recurrence after vagotomy is related to the number of parietal cells before vagotomy. A rationale is provided for antrectomy and vagotomy in duodenal ulcer patients with a high number of parietal cells.