tbuckley/cabot-search huggingface dataset:
Reactive perforating collagenosis
Authors: E. Young, F. Wojnarowska, P. Millard
Journal: British Journal of Dermatology (1985)

Journal Article Reactive perforating collagenosis Get access E. Young, E. Young Department of Dermatology, Wycombe General Hospital, High Wycombe Search for other works by this author on: Oxford Academic Google Scholar F. Wojnarowska, F. Wojnarowska Department of Dermatology, Wycombe General Hospital, High Wycombe Search for other works by this author on: Oxford Academic Google Scholar P. Millard P. Millard Department of Pathology, John Radcliffe Hospital, Oxford Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 113, Issue s29, 1 July 1985, Pages 44–45, https://doi.org/10.1111/j.1365-2133.1985.tb13014.x Published: 01 July 1985
S-Endoglin Expression Is Induced in Senescent Endothelial Cells and Contributes to Vascular Pathology
Authors: Francisco J. Blanco, María T. Grande, Carmen Langa, Barbara Oujo, Soraya Velasco, Alicia Rodriguez-Barbero, Eduardo Perez-Gomez, Miguel Quintanilla, Jose M. López-Novoa, Carmelo Bernabeu
Journal: Circulation Research (2008)

Senescence of endothelial cells (ECs) may contribute to age-associated cardiovascular diseases, including atherosclerosis and hypertension. The functional and gene expression changes associated with cellular senescence are poorly understood. Here, we have analyzed the expression, during EC senescence, of 2 different isoforms (L, long; S, short) of endoglin, an auxiliary transforming growth factor (TGF)-β receptor involved in vascular remodeling and angiogenesis. As evidenced by RT-PCR, the S/L ratio of endoglin isoforms was increased during senescence of human ECs in vitro, as well as during aging of mice in vascularized tissues. Next, the effect of S-endoglin protein on the TGF-β receptor complex was studied. As revealed by coimmunoprecipitation assays, S-endoglin was able to interact with both TGF-β type I receptors, ALK5 and ALK1, although the interaction with ALK5 was stronger than with ALK1. S-endoglin conferred a lower proliferation rate to ECs and behaved differently from L-endoglin in relation to TGF-β–responsive reporters with ALK1 or ALK5 specificities, mimicking the behavior of the endothelial senescence markers Id1 and plasminogen activator inhibitor-1. In situ hybridization studies demonstrated the expression of S-endoglin in the endothelium from human arteries. Transgenic mice overexpressing S-endoglin in ECs showed hypertension, decreased hypertensive response to NO inhibition, decreased vasodilatory response to TGF-β 1 administration, and decreased endothelial nitric oxide synthase expression in lungs and kidneys, supporting the involvement of S-endoglin in the NO-dependent vascular homeostasis. Taken together, these results suggest that S-endoglin is induced during endothelial senescence and may contribute to age-dependent vascular pathology.
Ocular sports injuries: the current picture
Authors: A Barr, P S Baines, P Desai, C J MacEwen
Journal: British Journal of Sports Medicine (2000)

To determine the recent incidence of eye injury due to sport in Scotland, identify any trend, and establish which sports are responsible for most injury? The type of injury and final visual outcome is also evaluated.A prospective observational study of ocular injuries sustained during sport was performed over a one year period. Only patients requiring hospital admission were included. Data were collected on a standardised proforma and entered into a central database. Patients were followed up for at least three months.Of 416 patients admitted because of ocular injury, 52 (12.5%) resulted from playing a sport. Although all racquet sports together accounted for 47.5% of these injuries, football was the single most common sport associated with ocular trauma, being responsible for 32.5% of cases. The most common clinical finding was macroscopic hyphaema occurring in 87.5% of patients. Overall the final visual acuity was 6/6 in 92.5% of patients.The incidence of eye injury due to sport at 12.5% is lower than previously reported, suggesting a change in the pattern of ocular trauma. Football is the single most common cause of ocular injury from sport in Scotland, but the wearing of protective headgear would be difficult to instigate. The incidence of hyphaema in sport related ocular trauma (87.5%) is almost double that of all ocular injury (47.8%), so the potential for serious visual loss as the result of a sports injury should not be underrated. Ophthalmologists have a role in protecting this young population at risk by actively encouraging the design and use of protective eyewear.
High Risk of Recurrence for Patients With Breast Cancer Who Have Human Epidermal Growth Factor Receptor 2–Positive, Node-Negative Tumors 1 cm or Smaller
Authors: Ana M. Gonzalez-Angulo, Jennifer K. Litton, Kristine R. Broglio, Funda Meric-Bernstam, Ronjay Rakkhit, Fatima Cardoso, Florentia Peintinger, Emer O. Hanrahan, Aysegul Sahin, Merih Guray, Denis Larsimont, Francesco Feoli, Heidi Stranzl, Thomas A. Buchholz, Vicente Valero, Richard Theriault, Martine Piccart-Gebhart, Peter M. Ravdin, Donald A. Berry, Gabriel N. Hortobagyi
Journal: Journal of Clinical Oncology (2009)

To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer.We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation.Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors.Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.
Endoscopic ultrasound for localisation of islet cell tumours.
Authors: J R Glover, P J Shorvon, W R Lees
Journal: Gut (1992)

In a prospective study endoscopic ultrasound localisation of pancreatic endocrine tumours was attempted in 21 patients with clinically suspected islet cell tumours. Most patients were referred after the failure of conventional imaging methods. Endoscopic ultrasound correctly identified the site of 12 of 15 insulinomas, one glucagonoma, and a diffuse pancreatic abnormality in a patient with multiple endocrine adenopathy. There were two true negative examinations and one technical failure. The sensitivity of endoscopic ultrasound was much greater than that of computed tomography or conventional transabdominal ultrasonography.
A Novel Gene Coding for a Fas Apoptosis Inhibitory Molecule (FAIM) Isolated from Inducibly Fas-resistant B Lymphocytes
Authors: Thomas J. Schneider, Gavin M. Fischer, Terrence J. Donohoe, Thomas P. Colarusso, Thomas L. Rothstein
Journal: The Journal of Experimental Medicine (1999)

The sensitivity of primary splenic B cells to Fas-mediated apoptosis is modulated in a receptor-specific fashion. Here we used a differential display strategy to detect cDNAs present in B cells rendered Fas resistant but absent in those rendered Fas sensitive. This led to the cloning and characterization of a novel 1.2-kb gene that encodes a Fas apoptosis inhibitory molecule (FAIM). faim-transfected BAL-17 B lymphoma cells were less sensitive by half or more to Fas-mediated apoptosis than were vector-transfected controls, using Fas ligand–bearing T cells or a cytotoxic anti-Fas antibody to trigger Fas, and this was associated with inhibition of Fas- induced poly-ADP ribose polymerase (PARP) cleavage. In primary B cells, the time course of faim mRNA and FAIM protein expression correlated with the induction of Fas resistance by surface (s)Ig engagement. Thus, FAIM is an inducible effector molecule that mediates Fas resistance produced by sIg engagement in B cells. However, faim is broadly expressed in various tissues and the faim sequence is highly conserved evolutionarily, suggesting that its role extends beyond lymphocyte homeostasis. As FAIM has no significant regions of homology to other gene products that modulate Fas killing, it appears to represent a distinct, new class of antiapoptotic protein.
Gefitinib as first-line treatment in advanced NSCLC with mutated EGFR
Authors: S. Naheed
Journal: Thorax (2010)

Non-small cell lung cancer (NSCLC) is a leading cause of cancer deaths. Standard cytotoxic chemotherapy has a response rate of only 20–35% and median survival among patients with advanced NSCLC is between 10 and 12 months. Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is used in patients with NSCLC with sensitive mutations of EGFR, and …
Dissociation of vasoconstrictor-stimulated basic fibroblast growth factor expression from hypertrophic growth in cultured vascular smooth muscle cells. Relevant roles of protein kinase C.
Authors: S Ali, M W Becker, M G Davis, G W Dorn
Journal: Circulation Research (1994)

Thromboxane A2 (TXA2) and angiotensin II (Ang II) stimulate vascular smooth muscle hypertrophy by upregulating endogenous synthesis of basic fibroblast growth factor (bFGF). Because mitogenic phorbol esters can also stimulate bFGF formation, we investigated the role of protein kinase C (PKC) in vascular smooth muscle cell (VSMC) bFGF formation and hypertrophy. Preliminary characterization of PKC isoform expression in VSMC by use of polymerase chain reaction identified PKC alpha, delta, epsilon, and zeta. Western analysis confirmed the presence of these isoforms in cultured VSMC lines and demonstrated downregulation of PKC alpha, delta, and epsilon by phorbol 12-myristate 13-acetate (PMA) but not TXA2 or Ang II. PKC activation with 100 nmol/L PMA stimulated VSMC mitogenesis measured as incorporation of [3H]leucine and [3H]thymidine and increased cell number. Like TXA2 and Ang II, PMA increased endogenous VSMC bFGF in a time-dependent manner, whereas an inactive phorbol ester had no such effect. Addition of an antisense oligodeoxynucleotide against bFGF prevented PMA-stimulated bFGF expression and inhibited PMA-stimulated growth, suggesting that bFGF synthesis is necessary for VSMC growth stimulated by PMA. To clarify the role of PKC in vasoconstrictor-stimulated VSMC production of bFGF and hypertrophy, PKC was down-regulated by prolonged exposure to PMA or was inhibited with calphostin C or staurosporine before the addition of TXA2 or Ang II. PKC inhibition prevented TXA2-stimulated and Ang II--stimulated VSMC hypertrophy without attenuating the observed increase in bFGF expression. Furthermore, PKC inhibition with calphostin C inhibited VSMC mitogenesis stimulated by exogenous bFGF.(ABSTRACT TRUNCATED AT 250 WORDS)
Characterization of a novel Hodgkin cell line, HD-MyZ, with myelomonocytic features mimicking Hodgkin's disease in severe combined immunodeficient mice.
Authors: R C Bargou, M Y Mapara, C Zugck, P T Daniel, M Pawlita, H Döhner, B Dörken
Journal: The Journal of Experimental Medicine (1993)

A novel Hodgkin cell line, designated HD-MyZ, was established from the pleural effusion of a 29-yr-old patient with Hodgkin's disease (HD) of nodular sclerosing type. The majority of cells grow adherently and display typical morphological characteristics of Reed-Sternberg (RS) and Hodgkin (H) cells, i.e., large multi- and mononucleated cells with prominent nucleoli. Immunofluorescence analysis revealed a myelomonocytoid immunophenotype (expression of CD13 and CD68, and lack of lymphoid markers). HD-MyZ cells strongly expressed restin, a recently described intermediate filament-associated protein, the expression of which is restricted to H cells, RS cells, and in vitro cultivated peripheral blood monocytes. In addition mRNA expression of c-fms (colony-stimulating factor 1 receptor) could be induced in HD-MyZ cells by phorbol myristate acetate (PMA) stimulation. Southern blot analysis did not detect rearrangement of T cell receptor beta and immunoglobulin H loci, thus demonstrating the lack of lymphoid commitment. HD-MyZ cells were also devoid of Epstein-Barr virus genomes. HD-MyZ cells constitutively express mRNAs for interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-5, IL-6, IL-7, IL-8, IL-10, IL-1 receptor (type I), and IL-6 receptor. Stimulation of cells with PMA increased mRNA expression as well as the secretion of IL-1 beta, IL-6, and IL-8, and induced the de novo expression of IL-8 receptors. Xenotransplantation into severe combined immunodeficient (SCID) mice by intravenous or subcutaneous inoculation led to development of disseminated tumors with infiltrative and destructive growth. In addition lymphadenopathy, pleural effusion, and infiltration of spleen were observed. Morphological and immunological analysis of tumor cells revealed the same features as HD-MyZ cells. This cell line might be an important tool for understanding the pathogenesis and biology of HD. In addition the SCID mice model might prove helpful in developing new therapeutic strategies.
Expansion of the miRNA Pathway in the Hemipteran Insect Acyrthosiphon pisum
Authors: S. Jaubert-Possamai, C. Rispe, S. Tanguy, K. Gordon, T. Walsh, O. Edwards, D. Tagu
Journal: Molecular Biology and Evolution (2010)

The pathways that allow short noncoding RNAs such as the microRNAs (miRNAs) to mediate gene regulation and control critical cellular and developmental processes involve a limited number of key protein components. These proteins are the Dicer-like RNases, double-stranded RNA (dsRNA)-binding proteins, and the Argonaute (AGO) proteins that process stem-loop hairpin transcripts of endogenous genes to generate miRNAs or long dsRNA precursors (either exogenous or endogenous). Comparative genomics studies of metazoans have shown the pathways to be highly conserved overall; the major difference observed is that the vertebrate pathways overlap in sharing a single Dicer (DCR) and AGO proteins, whereas those of insects appear to be parallel, with distinct Dicers and AGOs required for each pathway. The genome of the pea aphid is the first available for a hemipteran insect and discloses an unexpected expansion of the miRNA pathway. It has two copies of the miRNA-specific dicr-1 and ago1 genes and four copies of pasha a cofactor of drosha involved in miRNA biosynthesis. For three of these expansions, we showed that one copy of the genes diverged rapidly and in one case (ago1b) shows signs of positive selection. These expansions occurred concomitantly within a brief evolutionary period. The pea aphid, which reproduces by viviparous parthenogenesis, is able to produce several adapted phenotypes from one single genotype. We show by reverse transcriptase-polymerase chain reaction that all the duplicated copies of the miRNA machinery genes are expressed in the different morphs. Investigating the function of these novel genes offers an exciting new challenge in aphid biology.
Platelet Kainate Receptor Signaling Promotes Thrombosis by Stimulating Cyclooxygenase Activation
Authors: Henry Sun, AnneMarie Swaim, Jesus Enrique Herrera, Diane Becker, Lewis Becker, Kalyan Srivastava, Laura E. Thompson, Michelle R. Shero, Alita Perez-Tamayo, Bhoom Suktitipat, Rasika Mathias, Anis Contractor, Nauder Faraday, Craig N. Morrell
Journal: Circulation Research (2009)

Rationale: Glutamate is a major signaling molecule that binds to glutamate receptors including the ionotropic glutamate receptors; kainate (KA) receptor (KAR), the N -methyl- d -aspartate receptor, and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor. Each is well characterized in the central nervous system, but glutamate has important signaling roles in peripheral tissues as well, including a role in regulating platelet function. Objective: Our previous work has demonstrated that glutamate is released by platelets in high concentrations within a developing thrombus and increases platelet activation and thrombosis. We now show that platelets express a functional KAR that drives increased agonist induced platelet activation. Methods and Results: KAR induced increase in platelet activation is in part the result of activation of platelet cyclooxygenase in a mitogen-activated protein kinase–dependent manner. Platelets derived from KAR subunit knockout mice (GluR6 −/− ) are resistant to KA effects and have a prolonged time to thrombosis in vivo. Importantly, we have also identified polymorphisms in KAR subunits that are associated with phenotypic changes in platelet function in a large group of whites and blacks. Conclusions: Our data demonstrate that glutamate regulation of platelet activation is in part cyclooxygenase-dependent and suggest that the KAR is a novel antithrombotic target.
Protease-antiprotease imbalance in the lungs of children with cystic fibrosis.
Authors: P Birrer, N G McElvaney, A Rüdeberg, C W Sommer, S Liechti-Gallati, R Kraemer, R Hubbard, R G Crystal
Journal: American Journal of Respiratory and Critical Care Medicine (1994)

Cystic fibrosis (CF) is characterized in the lung by chronic purulent bronchitis culminating in pulmonary insufficiency. There is evidence to suggest that neutrophil elastase (NE) released by neutrophils on the respiratory epithelial surface plays a major role in the pathogenesis of this lung disease. This study sought to determine the age of onset of the chronic neutrophil-dominated inflammation in CF and the consequences to the NE-anti-NE screen on the respiratory epithelial surface of the CF lung. NE and anti-NE defensive molecules were evaluated in respiratory epithelial lining fluid (ELF) in 27 children with stable CF (1 to 18 yr of age). Despite normal antigenic concentrations of alpha 1-antitrypsin (alpha 1AT) and secretory leukoprotease inhibitor (SLPI), 25 of 27 children with CF had neutrophil-dominated inflammation (> 500 neutrophils/microliters ELF). Active NE was found in ELF in 20 of 27 children, including two of four aged 1 yr. Western blot analysis showed the majority of alpha 1AT and SLPI molecules to be complexed and/or degraded. These observations demonstrate that a chronic imbalance of the NE-anti-NE protective screen develops early on the respiratory epithelial surface in persons with CF and is likely well established by 1 yr of age, with resultant potential for lung damage.
In the Shadow of “Just Wars”: Violence, Politics and Humanitarian Action; Traditions, Values, and Humanitarian Action
Authors: Johan von Schreeb
Journal: BMJ (2004)

I found these two books in the mail after returning from an assessment of the heartbreaking humanitarian situation in the eastern parts of the Democratic Republic of Congo (DRC). The books partly deal with what I studied in DRC—how to describe, quantify, and communicate humanitarian needs to elicit better actions. The assessment challenge lies not only in the field but also in the concept of humanitarian action. Is humanitarian action a legal requirement that some authority or agency should be held responsible for, based on human rights? Or is it a voluntary response triggered by the humanitarian impulse to alleviate as much suffering as possible?

Humanitarian action during armed conflict has legal protection under international humanitarian law provided it is neutral, independent, and impartial. In contrast humanitarian action for those in deep poverty aggravated …
Tumor Metabolism and Blood Flow as Assessed by Positron Emission Tomography Varies by Tumor Subtype in Locally Advanced Breast Cancer
Authors: Jennifer M. Specht, Brenda F. Kurland, Susan K. Montgomery, Lisa K. Dunnwald, Robert K. Doot, Julie R. Gralow, Georgina K. Ellis, Hannah M. Linden, Robert B. Livingston, Kimberly H. Allison, Erin K. Schubert, David A. Mankoff
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Dynamic positron emission tomography (PET) imaging can identify patterns of breast cancer metabolism and perfusion in patients receiving neoadjuvant chemotherapy (NC) that are predictive of response. This analysis examines tumor metabolism and perfusion by tumor subtype. Experimental Design: Tumor subtype was defined by immunohistochemistry in 71 patients with locally advanced breast cancer undergoing NC. Subtype was defined as luminal [estrogen receptor (ER)/progesterone receptor (PR) positive], triple negative [TN; ER/PR negative, human epidermal growth factor receptor 2 (HER2) negative], and HER2 (ER/PR negative, HER2 overexpressing). Metabolic rate (MRFDG) and blood flow (BF) were calculated from PET imaging before NC. Pathologic complete response (pCR) to NC was classified as pCR versus other. Results: Twenty-five (35%) of 71 patients had TN tumors; 6 (8%) were HER2 and 40 (56%) were luminal. MRFDG for TN tumors was on average 67% greater than for luminal tumors (95% confidence interval, 9-156%) and average MRFDG/BF ratio was 53% greater in TN compared with luminal tumors (95% confidence interval, 9-114%; P &amp;lt; 0.05 for both). Average BF levels did not differ by subtype (P = 0.73). Most luminal tumors showed relatively low MRFDG and BF (and did not achieve pCR); high MRFDG was generally matched with high BF in luminal tumors and predicted pCR. This was not true in TN tumors. Conclusion: The relationship between breast tumor metabolism and perfusion differed by subtype. The high MRFDG/BF ratio that predicts poor response to NC was more common in TN tumors. Metabolism and perfusion measures may identify subsets of tumors susceptible and resistant to NC and may help direct targeted therapy. Clin Cancer Res; 16(10); 2803–10. ©2010 AACR.