tbuckley/cabot-search huggingface dataset:
Defective p53 Response and Apoptosis Associated with an Ataxia-Telangiectasia–like Phenotype
Authors: Nuri Gueven, Olivier J. Becherel, Geoff Birrell, Philip Chen, Giannino DelSal, James P. Carney, Padraic Grattan-Smith, Martin F. Lavin
Journal: Cancer Research (2006)

Abstract Ataxia-telangiectasia mutated (ATM), the protein defective in ataxia-telangiectasia, plays a central role in DNA damage response and signaling to cell cycle checkpoints. We describe here a cell line from a patient with an ataxia-telangiectasia–like clinical phenotype defective in the p53 response to radiation but with normal ATM activation and efficient downstream phosphorylation of other ATM substrates. No mutations were detected in ATM cDNA. A normal level of interaction between p53 and peptidyl-prolyl-isomerase Pin1 suggests that posttranslational modification was intact in these cells but operating at reduced level. Defective p53 stabilization was accompanied by defective induction of p53 effector genes and failure to induce apoptosis in response to DNA-damaging agents. Continued association between p53 and murine double minute-2 (Mdm2) occurred in irradiated ATL2ABR cells in response to DNA damage, and incubation with Mdm2 antagonists, nutlins, increased the stabilization of p53 and its transcriptional activity but failed to induce apoptosis. These results suggest that ATM-dependent stabilization of p53 and induction of apoptosis by radiation involve an additional factor(s) that is defective in ATL2ABR cells. (Cancer Res 2006; 66(6): 2907-12)
Taxonomic Subgroups within Psychosomatic Disease Entities: An Alternative Strategy to the Specificity Approach?
Authors: Adolf-Ernst Meyer
Journal: Psychotherapy and Psychosomatics (1984)

There are empirical indications that the well-known weaknesses of the different psychosomatic specificity theorems are linked to their presupposition of a one-to-one relationship between one specific psychosocial configuration and one definite disease entity. An alternative conceptualization is offered: The majority of the psychosocial phenomena found within a definite disease entity fall into a small group of perhaps half a dozen different patterns. Only a minority of cases show a high variation with many different patterns – some even individually unique. This alternative concept demands different research strategies and methods which are provided by taxometrics. This is illustrated with examples from a follow-up study of anorexia nervosa.
Charles Christopher Hunter
Authors: H. Newman
Journal: BMJ (2014)

We describe a case of a 15-year-old girl who presented to our clinic with long-standing right-sided rhinorrhoea which was occasionally foul-smelling and blood-stained with no other symptom of note. She had been treated many times with antibiotics. On examination, a rhinolith was discovered impacted posteriorly in right nasal cavity with mucopurulent discharge. Plain X-ray and later CT scan of paranasal sinuses confirmed the diagnosis but it was found to be large in size with irregular shape like a ‘staghorn’. It was removed under general anaesthesia and she recovered uneventfully. We also describe the review of literature.
Neonatal capsaicin treatment increases the severity of ozone-induced lung injury.
Authors: A Sterner-Kock, K R Vesely, M Y Stovall, E S Schelegle, J F Green, D M Hyde
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To test the hypothesis that lung sensory C fibers protect the small distal airways and alveoli from oxidant injury, we compared the effects of inhalation of ozone (1 ppm) or filtered air for 8 h on lung injury and lung inflammation in four groups of rats: (1) normal rats exposed to filtered air; (2) normal rats exposed to ozone; (3) rats treated as neonates with capsaicin (50 mg/kg, intraperitoneally) and subsequently exposed to filtered air; and (4) rats treated as neonates with capsaicin and subsequently exposed to ozone. All rats were allowed to recover in filtered air for 0, 4, 16, and 40 h before necropsy. Rats exposed to filtered air (Groups 1 and 3) showed normal airway and parenchyma structure. Normal untreated rats exposed to ozone showed a random distribution of mild, interstitial inflammatory changes and epithelial necrosis of bronchi and bronchiolar epithelium. However, rats treated with capsaicin and subsequently exposed to ozone demonstrated severe acute interstitial inflammation and epithelial coagulate necrosis in all airways, especially in small, peripheral airways and parenchyma; all of these changes were statistically significant. These findings support our hypothesis that lung sensory C fibers protect the distal airways from oxidant injury during acute ozone inhalation.
In vitro tolerance induction of neonatal murine B cells.
Authors: E S Metcalf, N R Klinman
Journal: The Journal of Experimental Medicine (1976)

The susceptibility of neonatal and adult B lymphocytes to tolerance induction was analyzed by a modification of the in vitro splenic focus technique. This technique permits stimulation of individual hapten-specific clonal precursor cells from both neonatal and adult donors. Neonatal or adult BALB/c spleen cells were adoptively transferred into irradiated, syngeneic, adult recipients which had been carrier-primed to hemocyanin (Hy), thus maximizing stimulation to the hapten 2,4-dinitrophenyl coupled by Hy (DNP-Hy). Cultures were initially treated with DNP on several heterologous (non-Hy) carriers and subsequently stimulated with DNP-Hy. Whereas the responsiveness of adult B cells was not diminished by pretreatment with any DNP conjugate, the majority of the neonatal B-cell response was abolished by in vitro culture with all of the DNP-protein conjugates. During the 1st wk of life, the ability to tolerize neonatal splenic B cells progressively decreased. Thus, tolerance in this system is: (a) restricted to B cells early in development; (b) established by both tolerogens and immunogens; (c) achieved at low (10(-9) M determinant) antigen concentrations; and (d) highly specific, discriminating between DNP- and TNP-specific B cells. We conclude that: (a) B lymphocytes, during their development, mature through a stage in which they are extremely susceptible to tolerogenesis; (b) the specific interaction of B-cell antigen receptors with multivalent antigens, while irrelevant to mature B cells, is tolerogenic to neonatal (immature) B cells unless antigen is concomitantly recognized by primed T cells; and (c) differences in the susceptibility of immature and mature B lymphocytes to tolerance induction suggest intrinsic differences between neonatal and adult B cells and may provide a physiologically relevant model for the study of tolerance to self-antigens.
An evidence base for reconsidering current follow-up guidelines for patients with cutaneous melanoma less than 05mm thick at diagnosis
Authors: J. Einwachter-Thompson, R.M. MacKie
Journal: British Journal of Dermatology (2008)

Background Despite current guidelines, there is uncertainty about the required duration and frequency of follow‐up visits for patients with invasive primary cutaneous melanoma < 0·5 mm thick. Objectives To review patients with invasive melanoma thinner than 0·5 mm followed for at least 5 years to provide an evidence base for considering modification of guidelines. Methods A retrospective review of 430 patients diagnosed in the west of Scotland during 1992–2001 with melanoma < 0·5 mm was carried out. Recurrence, deaths from melanoma and second primary melanomas were all identified. Results From 1992 to 2001, 430 melanomas < 0·5 mm thick at diagnosis were diagnosed out of a total of 3036 primary cutaneous melanomas. To date there have been 593 deaths from melanoma (19%) in the whole group. Five of these deaths were reported in patients with melanomas < 0·5 mm, but on pathological review two were thicker than 0·5 mm at diagnosis (1·5 and > 3 mm), and the remaining three patients all developed thicker second primary melanomas (2·7, 12·0 and 19·0 mm) with a recurrence pattern and timing indicating that these thicker primaries were the cause of death. Fourteen further patients developed a second primary melanoma, and 13 are currently alive and disease free, one dying of other causes. Conclusions Our data indicate that recurrence and subsequent death from melanomas < 0·5 mm is a very rare event, and that quarterly follow‐up for 3 years will yield very few events. Modification of current guideline recommendations are suggested to include a period of patient education concentrating on recognition of second primary tumours followed by rapid access to an expert opinion if required.
Abstract 3281: The Prognostic Characteristics of Cardiopulmonary Exercise Testing in Caucasian and African-American Patients with Heart Failure
Authors: Ross Arena, Jonathan Myers, Mary Ann Peberdy, Daniel Bensimhon, Paul Chase, Marco Guazzi
Journal: Circulation (2007)

Introduction: Peak oxygen consumption (VO 2 ) and the minute ventilation (VE)/carbon dioxide production (VCO 2 ) slope are prognostically important in the heart failure (HF) population. Hypothesis: We assessed the hypothesis that the prognostic characteristics of peak VO 2 and the VE/VCO 2 slope would be comparable between Caucasian and African-American subjects with HF. Methods: Four hundred and ninety one HF patients (339 Caucasian/152 African-American) underwent cardiopulmonary exercise testing and were tracked for major cardiac events for three years. Results: The following comparisons are reported as Caucasian vs. African-American subgroups, respectively. Age (56.7 ±14.4 vs. 47.1 ±13.4 years, p&lt;0.001) and ejection fraction (30.6 ±12.9 vs. 25.2 ±11.7%, p&lt;0.001) were significantly lower in the African-American subgroup. Peak VO 2 (15.7 ± 5.6 vs. 14.8 ± 5.7 mlO 2 ·kg −1 ·min −1 , p&lt;0.11) and the VE/VCO 2 slope (35.4 ±9.8 vs. 36.8 ±9.7, p=0.15) were not significantly different. There were 44 (annual event rate: 8.3%) major cardiac events (25 deaths/14 heart transplants/5 left ventricular assist device implantations) in the Caucasian subgroup and 25 (annual event rate: 10.1%) major cardiac events (18 deaths/5 heart transplants/2 left ventricular assist device implantations) in the African-American subgroup. Receiver operating characteristic (ROC) curve analysis and hazard ratios for exercise test variables are listed in Table 1 . Peak VO 2 and the VE/VCO 2 slope were prognostically significant in both subgroups. Conclusions: Despite differences in baseline characteristics between Caucasian and African-American subjects, the optimal prognostic threshold values of established exercise testing variables were similar. The VE/VCO 2 slope was the superior prognostic marker in both subgroups. While, peak VO 2 was prognostically significant in Caucasian and African-American subjects, its value was diminished in the latter subgroup.
Cediranib/AZD2171 Inhibits Bone and Brain Metastasis in a Preclinical Model of Advanced Prostate Cancer
Authors: Juan Juan Yin, Luhua Zhang, Jeeva Munasinghe, R. Ilona Linnoila, Kathleen Kelly
Journal: Cancer Research (2010)

Abstract Late stage or aggressive cancers exhibit metastatic growth at multiple sites, and the characterization of treatment response in various organs to drugs with potentially wide-ranging efficacy is needed. Tumor cells that induce angiogenesis are a common characteristic of metastatic disease, and clinically, antiangiogenic therapies have shown value in the setting of advanced cancer. However, recent preclinical studies have suggested that exposure to antiangiogenic drugs can increase tumor invasiveness and metastasis, making it important to determine which contexts antiangiogenic therapy is most appropriate. We describe here the effects of cediranib, a receptor tyrosine kinase inhibitor, in a model of advanced prostate cancer metastatic to skeleton and brain. Treatment with cediranib decreased metastatic tumor burden in the brain and bone, decreased cerebral vasogenic edema, and improved survival, despite increasing the invasive histology of brain metastases. Short-duration cediranib treatment given at the time of tumor cell dissemination was sufficient to inhibit the establishment and subsequent growth of bone metastases, although brain metastases were subject to rebound growth after the discontinuation of cediranib. Distinct growth patterns at different organ sites in the same animal showed that certain tumor microenvironments such as bone may be most amenable to interventions by anti–vascular endothelial growth factor (VEGF) therapies. In addition, anti-VEGF treatment may be of utility in decreasing the rapid growth of solid brain metastases and vasogenic edema in patients with advanced cancer, leading to reduced morbidity and associated clinical benefit. Cancer Res; 70(21); 8662–73. ©2010 AACR.
Vascular cell adhesion molecule-1 and smooth muscle cell activation during atherogenesis.
Authors: P Libby, H Li
Journal: Journal of Clinical Investigation (1993)

Vascular cell adhesion molecule-i: more than an endothelial-leukocyte adhesion molecule Initial studies of vascular cell adhesion molecule-1 (VCAM-) focused on its role in endothelial-leukocyte interactions ( 1, 2).A member of the immunoglobulin gene superfamily, this transmembrane protein on the surface of endothelial cells in- teracts with the f,3 integrin very late antigen-4 expressed by mononuclear leukocytes (3).In the context of atherosclerosis, this molecule warrants particular interest because of its early and focal expression on endothelial cells just where monocytes first accumulate at the sites of fatty streak formation (4, 5).The case of VCAM-1 illustrates a general principal that the restriction of expression of a molecule decreases as a function of time that the molecule is studied.Early surveys disclosed VCAM-1 expression not only on endothelium but on follicular dendritic cells in lymph nodes (6).Others reported VCAM-1 expression on skeletal muscle cells and postulated a role for this molecule in myogenesis (7).Elsewhere in this issue, O'Brien et al. report that in human atheroma not only endothelial cells, but certain lesional macrophages and smooth muscle cells also express VCAM-1 (8).In addition, atherogenic diets induce
Sent to Destroy
Authors: Monte S. Willis, W. H. Davin Townley-Tilson, Eunice Y. Kang, Jonathon W. Homeister, Cam Patterson
Journal: Circulation Research (2010)

The ubiquitin proteasome system (UPS) plays a crucial role in biological processes integral to the development of the cardiovascular system and cardiovascular diseases. The UPS prototypically recognizes specific protein substrates and places polyubiquitin chains on them for subsequent destruction by the proteasome. This system is in place to degrade not only misfolded and damaged proteins, but is essential also in regulating a host of cell signaling pathways involved in proliferation, adaptation to stress, regulation of cell size, and cell death. During the development of the cardiovascular system, the UPS regulates cell signaling by modifying transcription factors, receptors, and structural proteins. Later, in the event of cardiovascular diseases as diverse as atherosclerosis, cardiac hypertrophy, and ischemia/reperfusion injury, ubiquitin ligases and the proteasome are implicated in protecting and exacerbating clinical outcomes. However, when misfolded and damaged proteins are ubiquitinated by the UPS, their destruction by the proteasome is not always possible because of their aggregated confirmations. Recent studies have discovered how these ubiquitinated misfolded proteins can be destroyed by alternative "specific" mechanisms. The cytosolic receptors p62, NBR, and histone deacetylase 6 recognize aggregated ubiquitinated proteins and target them for autophagy in the process of "selective autophagy." Even the ubiquitination of multiple proteins within whole organelles that drive the more general macro-autophagy may be due, in part, to similar ubiquitin-driven mechanisms. In summary, the crosstalk between the UPS and autophagy highlight the pivotal and diverse roles the UPS plays in maintaining protein quality control and regulating cardiovascular development and disease.
ABO BLOOD GROUPS AND SKIN DISEASES.
Authors: MARJORY P. MacSWEEN, UNA A. SYME
Journal: British Journal of Dermatology (1965)

Journal Article ABO BLOOD GROUPS AND SKIN DISEASES. Get access MARJORY P. MacSWEEN, M.B., Ch.B., MARJORY P. MacSWEEN, M.B., Ch.B. Dermatology Department, University of Glasgow, Glasgow, W.2 Search for other works by this author on: Oxford Academic Google Scholar UNA A. SYME, M.A. UNA A. SYME, M.A. Dermatology Department, University of Glasgow, Glasgow, W.2 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 77, Issue 1, 1 January 1965, Pages 30–34, https://doi.org/10.1111/j.1365-2133.1965.tb14563.x Published: 01 January 1965
A WIRE LOOP FOR AURAL SNARES.
Authors: HAROLD WILSON
Journal: JAMA (1902)

In using the snare for the removal of aural polypi, it often has to be rethreaded several times during a single sitting, a procedure which is always more or less tedious or annoying. I have devised a loop with the ends of the wire twisted so that it may be inserted into any snare with a single open canula with very little trouble. A piece of malleable steel wire No. 36 or 40 (about a foot in length for the Blake snare) is doubled and twisted (best in a small lathe, holding the loop end between the fingers), leaving the loop of any desired size. These loops are so very easy to make that they are inexpensive, and may be made up and kept on hand in sufficient numbers to have them always ready. 32 West Adams Avenue.
Intravascular Coagulation in Acute Lupus Erythematosus
Authors: Charles L. Beall
Journal: JAMA (1975)

WE DESCRIBE a young woman with acute systemic lupus erythematosus (SLE) who also had complicating disseminated intravascular coagulation (DIC) that was both responsive to heparin and sensitive to its continued administration. Eventual response to simultaneously administered steroid therapy permitted successful discontinuance of anticoagulation treatment after 15 days. When last seen 1 1/2 years later, the patient was well while taking prednisone, 15 mg on alternate days. <h3>Report of a Case</h3> Following an attack of pharyngitis, a 19-year-old woman noticed small purpuric lesions on the fingers, cheeks, forehead, and ears. In the emergency department, her hematocrit value was 28.6%; white blood cell (WBC) count, 3,100/cu mm with 43 segmented neutrophils, 3 band cells, 49 lymphocytes, and adequate platelets; the corrected erythrocyte sedimentation rate was 32 mm/hr, and antistreptolysin O titer, 50 Todd units. A lupus erythematosus preparation was obtained and later reported as positive. She was instructed to return to the
Infectious Delivery and Expression of a 135 kb Human FRDA Genomic DNA Locus Complements Friedreich's Ataxia Deficiency in Human Cells
Authors: Silvia Gomez-Sebastian, Alfredo Gimenez-Cassina, Javier Diaz-Nido, Filip Lim, Richard Wade-Martins
Journal: Molecular Therapy (2007)

Friedreich's ataxia (FA) is the most common recessive ataxia, affecting 1-2 in 50,000 Caucasians, and there is currently no effective cure or treatment. FA results from a deficiency of the mitochondrial protein frataxin brought about by a repeat expansion in intron 1 of the FRDA gene. The main areas affected are the central nervous system (particularly the spinocerebellar system) and cardiac tissue. Therapies aimed at alleviating the neurological degeneration have proved unsuccessful to date. Here, we describe the construction and delivery of high capacity herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the entire 80 kb FRDA genomic locus, driven by the endogenous FRDA promoter and including all introns and flanking regulatory sequences within a 135 kb genomic DNA insert. FA patient primary fibroblasts deficient in frataxin protein and exhibiting sensitivity to oxidative stress were transduced at high efficiency by FRDA genomic locus vectors. Following vector transduction, expression of FRDA protein by immunofluorescence was shown. Finally, functional complementation studies demonstrated restoration of the wild-type cellular phenotype in response to oxidative stress in transduced FA patient cells. These results suggest the potential of the infectious bacterial artificial chromosome-FRDA vectors for gene therapy of FA.
SPONTANEOUS AMYLOIDOSIS IN DIFFERENTLY GROUPED AND TREATED DBA/2, BALB/c, AND CBA MICE AND THYMUS FIBROSIS IN ESTROGEN-TREATED BALB/c MALES
Authors: P. Ebbesen
Journal: The Journal of Experimental Medicine (1968)

Sex-segregated grouping of DBA/2, BALB/c, and CBA males caused rapid amyloid development and early death as compared with segregated grouped females or with males living individually in cages with several females. Grouping of several males in a cage with females also caused early death in amyloidosis indicating that the exposure of males to males and not the sexual isolation was important for the amyloid development. Both reserpine treatment and castration prolonged the survival time of sex-segregated grouped males. Estrogen treatment retarded amyloid development in sex-segregated males while spayed and androgen-treated spayed females showed only small amounts of amyloid. Treatment with chlortetracycline did not prevent amyloid development in grouped males. Thymectomy of sex-segregated males at 1 month of age gave inconclusive evidence of a prolongation of survival time. Egg-transferred DBA/2 mice reacted as conventional DBA/2 mice when grouped by sex segregation. Cells with abundant PAS-positive cytoplasm were found in the spleen, liver, and ovaries of mice of all strains but most prominently in CBA mice. Evidence for a direct conversion of these cells to amyloid was found. Estrogen-treated BALB/c males developed testicular tumors and thymus alterations including necrosis and depletion of lymphocytes, depletion of PAS cells, formation of large cysts containing necrotic nuclei, and intralobular fibrosis.
The Renal Papilla and Hypertension
Authors: Daniel T. O'Connor
Journal: JAMA (1981)

This volume is devoted to elucidating the role of the renal medulla in hypertension. The chapters probe the anatomy of the renal medulla, with emphasis on electron microscopic studies, and the biochemistry and physiology of putative medullary vasodilator substances, with particular stress on the prostaglandins and other "antihypertensive renomedullary substances," including antihypertensive polar and neutral renomedullary lipids. The chapters are generally written by noted authorities (Muirhead, Bohman, Zusman). The style seems quite uniformly lucid, with clear organization of ideas throughout. Many of the chapters dovetail in closely related areas of research (for example, renomedullary ultrastructure, renal interstitial cell morphology, renal interstitial cell lipids, and adaptations of all the above in various forms of experimental hypertension). While each chapter tries to address a separate issue, inevitable redundancies crop up, especially as concerns the history of work in the field and the chemistry and effects of antihypertensive renomedullary lipids. Among putative renal
Longitudinal Patterns of Skin Prick Test Sensitization in Early Childhood Predicts Risk for Asthma at Age 7
Authors: Jessica S. Tan, Cole Brokamp, Grace K. LeMasters, David I. Bernstein, Gurjit K. Khurana Hershey, James E. Lockey, Manuel S. Villareal, Patrick Ryan
Journal: Journal of Allergy and Clinical Immunology (2015)