tbuckley/cabot-search huggingface dataset:
The management of locally advanced pancreatic cancer: European Society of Digestive Oncology (ESDO) expert discussion and recommendations from the 14th ESMO/World Congress on Gastrointestinal Cancer, Barcelona
Authors: T. Seufferlein, J.L. Van Laethem, E. Van Cutsem, J.D. Berlin, M. Büchler, A. Cervantes, K. Haustermans, M. Hidalgo, E.M. O'Reilly, C. Verslype, W. Schmiegel, P. Rougier
Journal: Annals of Oncology (2014)
Porous nanocrystalline silicon membranes as highly permeable and molecularly thin substrates for cell culture
Authors: A.A. Agrawal, B.J. Nehilla, K.V. Reisig, T.R. Gaborski, D.Z. Fang, C.C. Striemer, P.M. Fauchet, J.L. McGrath
Journal: Biomaterials (2010)
Respiratory infections and their influence on lung function in children: a multiple regression analysis.
Authors: J W Yarnell, A S St Leger
Journal: Thorax (1981)

The relationship between a history of respiratory infections (and associated variables) in children and lung function in later life was examined in a study among 228 children aged 7 to 11 years. In a multiple regression analysis only a few variables showed marked and consistent effects on lung function. Respiratory tract infections showed increasing impairment of lung function with repeated infections, but the impairment was smaller than that caused by current asthma.
Activation of the PI3K/AKT Pathway Induces Urothelial Carcinoma of the Renal Pelvis: Identification in Human Tumors and Confirmation in Animal Models
Authors: Chao-Nan Qian, Kyle A. Furge, Jared Knol, Dan Huang, Jindong Chen, Karl J. Dykema, Eric J. Kort, Aaron Massie, Sok Kean Khoo, Kristin Vanden Beldt, James H. Resau, John Anema, Richard J. Kahnoski, Hans Morreau, Philippe Camparo, Eva Comperat, Mathilde Sibony, Yves Denoux, Vincent Molinie, Annick Vieillefond, Charis Eng, Bart O. Williams, Bin Tean Teh
Journal: Cancer Research (2009)

Urothelial carcinoma of the renal pelvis is a deadly disease with an unclear tumorigenic mechanism. We conducted gene expression profiling on a set of human tumors of this type and identified a phosphatidylinositol 3-kinase (PI3K)/AKT activation expression signature in 76.9% (n = 13) of our samples. Sequence analysis found both activating mutations of PIK3CA (13.6%, n = 22) and loss of heterozygosity at the PTEN locus (25%, n = 8). In contrast, none of the other subtypes of kidney neoplasms (e.g., clear-cell renal cell carcinoma) harbored PIK3CA mutations (n = 87; P < 0.001). Immunohistochemical analysis of urothelial carcinoma samples found loss of PTEN protein expression (36.4%, n = 11) and elevation of phosphorylated mammalian target of rapamycin (mTOR; 63.6%, n = 11). To confirm the role of the PI3K/AKT pathway in urothelial carcinoma, we generated mice containing biallelic inactivation of Pten in the urogenital epithelia. These mice developed typical renal pelvic urothelial carcinomas, with an incidence of 57.1% in mice older than 1 year. Laser capture microdissection followed by PCR confirmed the deletion of Pten exons 4 and 5 in the animal tumor cells. Immunohistochemical analyses showed increased phospho-mTOR and phospho-S6K levels in the animal tumors. Renal lymph node metastases were found in 15.8% of the animals with urothelial carcinoma. In conclusion, we identified and confirmed an important role for the PI3K/AKT pathway in the development of urothelial carcinoma and suggested that inhibitors of this pathway (e.g., mTOR inhibitor) may serve as effective therapeutic agents.
Management of acute pancreatitis
Authors: Derek A O'Reilly, Andrew N Kingsnorth
Journal: BMJ (2004)

Role of antibiotics remains controversial 

Acute pancreatitis is a common surgical emergency. The incidence in the United Kingdom has been reported to be as high as 38 per 100 000 per year and increasing. Around 25% of patients develop severe or life threatening complications, requiring support in high dependency or intensive care units. Mortality has fallen from 25-30%, 30 years ago, but has remained at 6-10% for most of the past two decades.1 The initial improvement did not occur because of any specific treatment for acute pancreatitis but because of improved supportive treatment, especially advances in critical care. This supportive treatment may include a role for prophylaxis with antibiotics in acute pancreatitis.

The rationale for prophylaxis with antibiotics is based on the fact that mortality for infected pancreatic necrosis is higher than that for sterile necrosis, and a potential window of opportunity exists during the first to third weeks for prevention of infection by giving prophylactic antibiotics. A recent Cochrane review supports this view.2 Despite this, the …
Aryl Hydrocarbon Receptor Is Activated by Glucose and Regulates the Thrombospondin-1 Gene Promoter in Endothelial Cells
Authors: Pankaj Dabir, Tina E. Marinic, Irene Krukovets, Olga I. Stenina
Journal: Circulation Research (2008)

Hyperglycemia is an independent risk factor for development of diabetic vascular complications. The molecular mechanisms that are activated by glucose in vascular cells and could explain the development of vascular complications are still poorly understood. A putative binding site for the transcription factor aryl hydrocarbon receptor (AhR) was identified in the glucose-responsive fragment of the promoter of thrombospondin-1, a potent antiangiogenic and proatherogenic protein involved in development of diabetic vascular complications. AhR was expressed in aortic endothelial cells (ECs), activated, and bound to the promoter in response to high glucose stimulation of ECs. The constitutively active form of AhR induced activation of the thrombospondin-1 gene promoter. In response to high glucose stimulation, AhR was found in complex with Egr-1 and activator protein-2, which are 2 other nuclear transcription factors activated by glucose in ECs that have not been previously detected in complex with AhR. The activity of the DNA-binding complex was regulated by glucose through the activation of hexosamine pathway and intracellular glycosylation. This is the first report of activation of AhR (a receptor for xenobiotic compounds) by a physiological stimulus. This report links the activation of AhR to the pathological effects of hyperglycemia in the vasculature.
Neurocognitive Functioning in Adult Survivors of Childhood Non-Central Nervous System Cancers
Authors: Nina S. Kadan-Lottick, Lonnie K. Zeltzer, Qi Liu, Yutaka Yasui, Leah Ellenberg, Gerard Gioia, Leslie L. Robison, Kevin R. Krull
Journal: JNCI Journal of the National Cancer Institute (2010)

We sought to measure self-reported neurocognitive functioning among survivors of non-central nervous system (CNS) childhood cancers, overall and compared with a sibling cohort, and to identify factors associated with worse functioning. In a retrospective cohort study, 5937 adult survivors of non-CNS cancers and 382 siblings completed a validated neuropsychological instrument with subscales in task efficiency, emotional regulation, organization, and memory. Scores were converted to T scores; scores in the worst 10% of siblings’ scores (ie, T score ≥63) were defined as impaired. Non-CNS cancer survivors and siblings were compared with multivariable linear regression and log-binomial regression. Among survivors, log-binomial models assessed the association of patient and treatment factors with neurocognitive dysfunction. All statistical tests were two-sided. Non-CNS cancer survivors had similar or slightly worse (<0.5 standard deviation) mean test scores for all four subscales than siblings. However, frequencies of impaired survivors were approximately 50% higher than siblings in task efficiency (13.0% of survivors vs 7.3% of siblings), memory (12.5% vs 7.6%), and emotional regulation (21.2% vs 14.4%). Impaired task efficiency was most often identified in patients with acute lymphoblastic leukemia who received cranial radiation therapy (18.1% with impairment), myeloid leukemia who received cranial radiation therapy (21.2%), and non-Hodgkin lymphoma (13.9%). In adjusted analysis, diagnosis age of younger than 6 years, female sex, cranial radiation therapy, and hearing impairment were associated with impairment. A statistically and clinically significantly higher percentage of self-reported neurocognitive impairment was found among survivors of non-CNS cancers than among siblings.
Clinical Judgment and Decision Making
Authors: Howard N. Garb
Journal: Annual Review of Clinical Psychology (2004)

When clinical psychologists make judgments, are they likely to be correct or incorrect? The following topics are reviewed: (a) methodological advances in evaluating the validity of descriptions of personality and psychopathology, (b) recent findings on the cognitive processes of clinicians, and (c) the validity of judgments and utility of decisions made by mental health professionals. Results from research on clinical judgment and decision making and their relationship to conflicts within the field of clinical psychology are discussed.
Diabetes and disenrollment in a health maintenance organization setting: a 4-year longitudinal study with a matched cohort.
Authors: A P Legorreta, Y Y Meng, K M Leung, Z Lin, M B Davidson
Journal: Diabetes Care (1999)

OBJECTIVE: The increasing enrollment of Medicare beneficiaries in health maintenance organizations (HMOs) in recent years has caused concern about whether HMOs and their providers have created an unfavorable environment for members who are chronically ill. This study was designed to examine whether there are any differences in disenrollment rates among enrollees with diabetes and enrollees without diabetes. RESEARCH DESIGN AND METHODS: This was a 4-year longitudinal follow-up study with a matched cohort. Medicare beneficiaries (aged &amp;gt; or =65 years) with diabetes identified through pharmacy records in 1994 were matched with a comparison group according to age, sex, comorbidities, and type of provider groups in an HMO in California. RESULTS: The overall distribution of the characteristics of members in the diabetic and matched nondiabetic group is almost identical. The matched-pair chi2 tests indicated that there were no statistical differences in disenrollment rates between diabetic and nondiabetic members during all three follow-up periods (P = 0.16-0.85). CONCLUSIONS: We found that the HMO members with diabetes did not disenroll from the HMO at a higher rate than those without diabetes. The findings should alleviate some of the concern that HMOs and their contracted providers have created an unattractive environment for members who have chronic diseases such as diabetes.
Pleural fluid interferon-gamma and tumour necrosis factor-alpha in tuberculous and rheumatoid pleurisy
Authors: T Soderblom, P Nyberg, AM Teppo, M Klockars, H Riska, T Pettersson
Journal: European Respiratory Journal (1996)

Tuberculous and rheumatoid pleural effusions show features suggesting a strong local cellular immune response. Pleural fluid (Pf) from patients with tuberculosis, rheumatoid arthritis (RA) and other diseases were compared with respect to interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha). Immunoassays were used to determine Pf-IFN-gamma and Pf-TNF-alpha in 102 patients, including 11 with RA, 31 with verified tuberculosis, 23 with suspected tuberculosis, 11 with pneumonia, 14 with lung cancer and 12 with congestive heart failure. Measurable Pf-IFN-gamma occurred exclusively in patients with verified (median 1.8 ng x mL-1; 95% confidence interval (95% CI) 0.63-4.0 ng x mL-1) or suspected (0.37 ng x mL-1; 95%CI 0-0.7 ng x mL-1) tuberculosis. The highest median Pf-IFN-gamma was observed in those patients who showed a positive pleural fluid culture for Mycobacterium tuberculosis. In pleural effusions due to other diseases, including RA, IFN-gamma was undetectable. The highest Pf-TNF-alpha occurred in verified tuberculosis (median 198 ng x L-1; 95% CI 169-222 ng x L-1) and RA (210 ng x L-1; 95% CI 147-231 ng x L-1). Pleural fluid interferon-gamma is a highly useful marker for diagnosing tuberculous pleurisy. Although tuberculous and rheumatoid pleural effusions share several biochemical features, they are strikingly different with respect to interferon-gamma.
Phospholipase C delta-4 overexpression upregulates ErbB1/2 expression, Erk signaling pathway, and proliferation in MCF-7 cells.
Authors: David W Leung, Chris Tompkins, Jim Brewer, Alexey Ball, Mike Coon, Valerie Morris, David Waggoner, Jack W Singer
Journal: Molecular Cancer (2004)

The expression of the rodent phosphoinositide-specific phospholipase C δ-4 (PLCδ4) has been found to be elevated upon mitogenic stimulation and expression analysis have linked the upregulation of PLCδ4 expression with rapid proliferation in certain rat transformed cell lines. The human homologue of PLCδ4 has not been extensively characterized. Accordingly, we investigate the effects of overexpression of human PLCδ4 on cell signaling and proliferation in this study. The cDNA for human PLCδ4 has been isolated and expressed ectopically in breast cancer MCF-7 cells. Overexpression of PLCδ4 selectively activates protein kinase C-φ and upregulates the expression of epidermal growth factor receptors EGFR/erbB1 and HER2/erbB2, leading to constitutive activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) pathway in MCF-7 cells. MCF-7 cells stably expressing PLCδ4 demonstrates several phenotypes of transformation, such as rapid proliferation in low serum, formation of colonies in soft agar, and capacity to form densely packed spheroids in low-attachment plates. The growth signaling responses induced by PLCδ4 are not reversible by siRNA. Overexpression or dysregulated expression of PLCδ4 may initiate oncogenesis in certain tissues through upregulation of ErbB expression and activation of ERK pathway. Since the growth responses induced by PLCδ4 are not reversible, PLCδ4 itself is not a suitable drug target, but enzymes in pathways activated by PLCδ4 are potential therapeutic targets for oncogenic intervention.
Immunohistochemical localization of cytokeratins and involucrin in calcifying epithelioma: comparative studies with normal skin
Authors: S. WATANABE, K. WAGATSUMA, H. TAKAHASHI
Journal: British Journal of Dermatology (2006)

The expression of cytokeratins and involucrin varies greatly in different epithelia, and this raises the possibility that detailed analysis of these epidermal proteins might provide a means of identifying various skin tumours. The present study was conducted to determine the immunohistochemical distribution of cytokeratins and involucrin in calcifying epithelioma of Malherbe, in order to elucidate the nature and differentiation of this tumour. To correlate the immunohistochemical profile with the most frequent histological patterns, we categorized the basophilic, transitional, shadow, and squamoid cells, and the shreds of keratin. Comparative studies with normal skin showed that the shadow and transitional cells corresponded to hair cortex cells, the squamoid cells to the outer root sheath, the basophilic cells adjacent to the stroma to the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the follicles, and the basophilic cells adjacent to the transitional cells to the hair matrix. The expression of cytokeratins in most shreds of keratin was similar to that in squamoid cells. Calcifying epithelioma was, therefore, shown to be composed of tumour cells differentiating into both the hair cortex and outer root sheath. These tumour cells were differentiated from basophilic cells, which showed the same staining patterns as the outermost cell layer of the outer root sheath between the lower permanent portion and upper transient portion of the hair follicles, supporting the hypothesis that the keratinocytes in the outermost cell layer can differentiate into the transitional portion of the follicle and anagen hair.
Tagging Single Nucleotide Polymorphisms in Cell Cycle Control Genes and Susceptibility to Invasive Epithelial Ovarian Cancer
Authors: Simon A. Gayther, Honglin Song, Susan J. Ramus, Susan Krüger Kjaer, Alice S. Whittemore, Lydia Quaye, Jonathan Tyrer, Danielle Shadforth, Estrid Hogdall, Claus Hogdall, Jan Blaeker, Richard DiCioccio, Valerie McGuire, Penelope M. Webb, Jonathan Beesley, Adele C. Green, David C. Whiteman, Marc T. Goodman, Galina Lurie, Michael E. Carney, Francesmary Modugno, Roberta B. Ness, Robert P. Edwards, Kirsten B. Moysich, Ellen L. Goode, Fergus J. Couch, Julie M. Cunningham, Thomas A. Sellers, Anna H. Wu, Malcolm C. Pike, Edwin S. Iversen, Jeffrey R. Marks, Montserrat Garcia-Closas, Louise Brinton, Jolanta Lissowska, Beata Peplonska, Douglas F. Easton, Ian Jacobs, Bruce A.J. Ponder, Joellen Schildkraut, C. Leigh Pearce, Georgia Chenevix-Trench, Andrew Berchuck, Paul D.P. Pharoah
Journal: Cancer Research (2007)

High-risk susceptibility genes explain <40% of the excess risk of familial ovarian cancer. Therefore, other ovarian cancer susceptibility genes are likely to exist. We have used a single nucleotide polymorphism (SNP)-tagging approach to evaluate common variants in 13 genes involved in cell cycle control-CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D-and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotyped in three studies from the United Kingdom, United States, and Denmark ( approximately 1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States ( approximately 2,000 cases and approximately 3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk [OR, 0.91 (0.85-0.98) for rs3731257; and OR, 0.93 (0.87-0.995) for rs2066827]. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies.
Carotid sinus hypersensitivity: evaluation of the vasodepressor component.
Authors: A Almquist, C Gornick, W Benson, A Dunnigan, D G Benditt
Journal: Circulation (1985)

The basis of the vasodepressor response in patients with carotid sinus hypersensitivity (CSH) is unknown, and prevention of recurrent vasodepressor-induced hypotension in these patients has not been possible. In this study we assessed the effectiveness of atrioventricular sequential pacing and pharmacologic interventions in the prevention of carotid sinus massage (CSM)-induced vasodepressor responses in eight patients with CSH. Maintenance of constant heart rate (80 beats/min) and atrioventricular synchrony (atrioventricular interval 150 msec) with sequential pacing did not significantly alter mean CSM-induced fall in systolic pressure (CSM control, -60 +/- 12 mm Hg vs CSM with atrioventricular sequential pacing, -48 +/- 19 mm Hg). Similarly, neither pharmacologic muscarinic blockade nor combined muscarinic and beta-adrenergic blockade significantly attenuated CSM-induced fall in systolic pressure (CSM with atropine, -43 +/- 16 mm Hg; CSM with atropine plus propranolol, -47 +/- 18 mm Hg; both p = NS vs atrioventricular sequential pacing alone). On the other hand, intravenous norepinephrine and oral ephedrine blunted the CSM-induced drop in systolic pressure (CSM with norepinephrine, -19 +/- 12 mm Hg; CSM with ephedrine, -21 +/- 11 mm Hg; both p less than .01 vs atrioventricular sequential pacing alone). Thus, vasodepressor responses were not prevented by control of heart rate, maintenance of atrioventricular synchrony, pharmacologic muscarinic blockade, or combined muscarinic and beta-adrenergic blockade, but were attenuated by drugs believed to be predominantly alpha-adrenergic agonists. Consequently, atrioventricular sequential pacing alone may be inadequate to prevent hypotension in patients with pronounced vasodepressor responses, whereas administration of vasoconstrictors such as ephedrine may diminish symptoms.
Effect of BCG vaccination on risk of Mycobacterium tuberculosis infection in children with household tuberculosis contact: a prospective community-based study
Authors: Ahmet Soysal, Kerry A Millington, Mustafa Bakir, Davinder Dosanjh, Yasemin Aslan, Jonathan J Deeks, Serpil Efe, Imogen Staveley, Katie Ewer, Ajit Lalvani
Journal: The Lancet (2005)
Regulation of immunoglobulin E antibody synthesis in man by antiidiotypic antibodies.
Authors: R S Geha, M Comunale
Journal: Journal of Clinical Investigation (1983)

The effect of rabbit antiidiotypic antibody raised against human IgG F(ab')2 anti-tetanus toxoid (TT) antibodies on the in vitro synthesis of TT-specific IgE antibody by peripheral blood lymphocytes (PBL) was examined in three subjects. Two of these subjects were allergic twins whose sera persistently contained IgE anti-TT antibodies. The third subject was a nonallergic individual who had a slightly elevated serum IgE (250 IU/ml) and who exhibited a transient serum IgE anti-TT response after booster immunization with TT. After appropriate absorptions rabbit anti-idiotype (Id) IgG reacted with anti-TT antibodies of both IgG and IgE isotypes in an idiotype- and antigen-specific fashion. PBL and B cells from the three subjects studied spontaneously synthesized TT-specific IgE in culture. In all three cases, adsorption of B cells over plastic plates coated with anti-Id before culture specifically decreased the synthesis of IgE antibodies to TT but did not affect the synthesis of IgE antibodies to ragweed antigen E by PBL from the twin allergic subjects. Addition of anti-Id to cultures of PBL from all three subjects specifically inhibited the synthesis of TT-specific IgE. This inhibition was shown to be exerted both at the level of the B cells and via the generation of antigen-specific suppressor T cells from radiosensitive precursors. The present results indicate that the synthesis of antigen-specific IgE in man is subject to regulation by idiotypic anti-idiotypic interactions that can involve both B and T lymphocytes.
Epinephrine Use in Clinical Trials of Sublingual Immunotherapy Tablets for Treatment of Allergic Rhinitis with/without Conjunctivitis
Authors: Jennifer Maloney, Thomas B. Casale, Richard F. Lockey, Harold S. Nelson, Bodil Svanholm Fogh, Amarjot Kaur, Hendrik Nolte
Journal: Journal of Allergy and Clinical Immunology (2015)
Rectal reaction to injected ulcerative colitis leucocytes and plasma.
Authors: S Fink, W J Donnelly, V R Jablokow
Journal: Gut (1967)

EDITORIAL COMMENT In patients with ulcerative colitis viable leucocytes from their peripheral blood injected into the rectal mucosa caused a local reaction which was not seen after injection with plasma, a phenomenon which needs further study.Leucocytes from the peripheral blood of patients with chronic ulcerative colitis are cytotoxic for foetal colon cells in tissue culture (Perlmann and Broberger, 1963).This report describes the effect of autologous ulcerative colitis leucocytes and cell-free plasma upon intact rectal mucosa.