tbuckley/cabot-search huggingface dataset:
Genetic overlap between autism, schizophrenia and bipolar disorder
Authors: Liam S Carroll, Michael J Owen
Journal: Genome Medicine (2009)

There is strong evidence that genetic factors make substantial contributions to the etiology of autism, schizophrenia and bipolar disorders, with heritability estimates being at least 80% for each. These illnesses have complex inheritance, with multiple genetic and environmental factors influencing disease risk; however, in psychiatry, complex genetics is further compounded by phenotypic complexity. Autism, schizophrenia and bipolar disorder are effectively syndromic constellations of symptoms that define groups of patients with broadly similar outcomes and responses to treatment. As such the diagnostic categories are likely to be heterogeneous and the boundaries between them somewhat arbitrary. Recent applications of whole-genome technologies have discovered rare copy number variants and common single-nucleotide polymorphisms that are associated with risk of developing these disorders. Furthermore, these studies have shown an overlap between the genetic loci and even alleles that predispose to the different phenotypes. The findings have several implications. First, they show that copy number variations are likely to be important risk factors for autism and schizophrenia, whereas common single-nucleotide polymorphism alleles have a role in all disorders. Second, they imply that there are specific genetic loci and alleles that increase an individual's risk of developing any of these disorders. Finally, the findings suggest that some of the specific genetic loci implicated so far encode proteins, such as neurexins and neuroligins, that function in synaptic development and plasticity, and therefore may represent a common biological pathway for these disorders.
Histones to the cytosol: exportin 7 is essential for normal terminal erythroid nuclear maturation
Authors: Shilpa M. Hattangadi, Sandra Martinez-Morilla, Heide Christine Patterson, Jiahai Shi, Karly Burke, Amalia Avila-Figueroa, Srividhya Venkatesan, Junxia Wang, Katharina Paulsen, Dirk Görlich, Maki Murata-Hori, Harvey F. Lodish
Journal: Blood (2014)
Effects of Delayed Rectifier Current Blockade by E-4031 on Impulse Generation in Single Sinoatrial Nodal Myocytes of the Rabbit
Authors: E. Etienne Verheijck, Antoni C.G. van Ginneken, Jan Bourier, Lennart N. Bouman
Journal: Circulation Research (1995)

Abstract The role of the delayed rectifier current (I K ) in impulse generation was studied in single sinoatrial nodal myocytes of the rabbit. We used the class III antiarrhythmic drug E-4031, which blocks I K in rabbit ventricular myocytes. In single sinoatrial nodal cells, E-4031 (0.1 μmol/L) significantly prolonged cycle length and action potential duration, depolarized maximum diastolic potential, and reduced both the upstroke velocity of the action potential and the diastolic depolarization rate. Half of the cells were arrested completely. At higher concentrations (1 and 10 μmol/L), spontaneous activity ceased in all cells. Three ionic currents fundamental for pacemaking, ie, I K , the long-lasting inward calcium current (I Ca,L ), and the hyperpolarization-activated current (I f ), were studied by using the whole-cell and amphotericin–perforated patch technique. E-4031 blocked part of the outward current during depolarizing steps as well as the tail current upon subsequent repolarization (I TD ) in a dose-dependent manner. E-4031 (10 μmol/L) depressed I TD (88±4%) (n=6), reduced peak I Ca,L at 0 mV (29±15%) (n=4), but did not affect I f . Lower concentrations did not affect I Ca,L . Additional use of 5 μmol/L nifedipine demonstrated that I TD is carried in part by a calcium-sensitive current. Interestingly, complete blockade of I K and I Ca,L unmasked the presence of a background current component with a reversal potential of −32±5.4 mV (n=8) and a conductance of 39.5±5.6 pS/pF, which therefore can contribute both to the initial part of repolarization and to full diastolic depolarization. In conclusion, I K in conjunction with an inward background current plays an essential role in maintaining normal automaticity.
CD3 Ligation on Immature Thymocytes Generates Antagonist-like Signals Appropriate for CD8 Lineage Commitment, Independently of T Cell Receptor Specificity
Authors: M. Albert Basson, Ursula Bommhardt, Michael S. Cole, J. Yun Tso, Rose Zamoyska
Journal: The Journal of Experimental Medicine (1998)

The signals that direct differentiation of T cells to the CD4 or CD8 lineages in the thymus remain poorly understood. Although it has been relatively easy to direct differentiation of CD4 single positive (CD4+) cells using combinations of antibodies and pharmacological agents that mimic receptor engagements, equivalent stimuli do not induce efficient maturation of CD8+ cells. Here we report that, irrespective of the MHC-restriction specificity of the TCR, differentiation of mature CD8+ thymocytes can be induced by ligation of CD3 polypeptides on immature thymocytes with a F(ab′)2 reagent (CD3fos-F(ab′)2). The tyrosine phosphorylation patterns stimulated by CD3fos-F(ab′)2 have been shown to resemble those delivered to mature T cells by antagonist peptides, which are known to direct positive selection of CD8+ cells, and we can show that this reagent exhibits potent antagonistic-like activity for primary T cell responses. Our results suggest a distinction in the signals that specify lineage commitment in the thymus. We present a model of thymocyte differentiation that proposes that the relative balance of signals delivered by TCR engagement and by p56lck activation is responsible for directing commitment to the CD8 or CD4 lineages.
Childhood Leukemia Incidence in Britain, 1974–2000: Time Trends and Possible Relation to Influenza Epidemics
Authors: Mary E. Kroll, Gerald J. Draper, Charles A. Stiller, Michael F. G. Murphy
Journal: JNCI Journal of the National Cancer Institute (2006)

Time trends in incidence of disease may cast light on etiology. We investigated time trends in childhood leukemia by using Poisson regression methods to analyze data from the National Registry of Childhood Tumours, a long-standing high-quality registry that covers the whole childhood population of Britain. During 1974-2000, the average annual percentage change in rate (AAC) of childhood acute lymphoblastic leukemia (ALL) in Britain was 0.7% (95% confidence interval [CI] = 0.4 to 1.0). This increase was apparently driven by the "common" subtype (expressing the CD10 antigen) of precursor B-cell ALL, for which the estimated AAC during 1980-1996 was 1.4% (95% CI = 0.8 to 2.0). There was no statistically significant time trend in other subtypes of ALL combined (1980-1996) or in acute myeloid leukemia (1974-2000). Small peaks in incidence of ALL in 1976 and 1990 coincided with years immediately following influenza epidemics. These results are consistent with hypotheses that some childhood leukemia may be triggered by infection occurring close to the time of diagnosis of leukemia, particularly in conditions of low herd immunity, and raise the possibility that contact with influenza shortly before the diagnosis of leukemia may sometimes be involved.
Rosacea fulminans in pregnancy
Authors: V.J. Lewis, S.A. Holme, A. Wright, A.V. Anstey
Journal: British Journal of Dermatology (2004)

Journal Article Rosacea fulminans in pregnancy Get access V.J. Lewis, V.J. Lewis Departments of Dermatology and Obstetrics and Gynaecology, Royal Gwent Hospital, Cardiff Road, Newport, NP20 2UB, U.K Dr V. J. Lewis, Specialist Registrar, Department of Dermatology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, U.K. E‐mail: vjlewis65@hotmail.com Search for other works by this author on: Oxford Academic Google Scholar S.A. Holme, S.A. Holme Departments of Dermatology and Obstetrics and Gynaecology, Royal Gwent Hospital, Cardiff Road, Newport, NP20 2UB, U.K Search for other works by this author on: Oxford Academic Google Scholar A. Wright, A. Wright Departments of Dermatology and Obstetrics and Gynaecology, Royal Gwent Hospital, Cardiff Road, Newport, NP20 2UB, U.K Search for other works by this author on: Oxford Academic Google Scholar A.V. Anstey A.V. Anstey Departments of Dermatology and Obstetrics and Gynaecology, Royal Gwent Hospital, Cardiff Road, Newport, NP20 2UB, U.K Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 151, Issue 4, 1 October 2004, Pages 917–919, https://doi.org/10.1111/j.1365-2133.2004.06190.x Published: 01 October 2004 Article history Accepted: 27 February 2004 Published: 01 October 2004
Metabolism and uptake of adenosine triphosphate and adenosine by porcine aortic and pulmonary endothelial cells and fibroblasts in culture.
Authors: Y Dieterle, C Ody, A Ehrensberger, H Stalder, A F Junod
Journal: Circulation Research (1978)

Incubation of cultured porcine aortic and pulmonary endothelial cells and mediastinal fibroblasts in the presence of 'H-ATP resulted in the hydrolysis of the nucleotide and the appearance of adenosine, while, simultaneously, a saturable, temperature-dependent uptake of radioactivity was taking place.The same pattern was observed in the three cell types.Adenosine uptake was studied in the same cell populations and also found to be a saturable, temperature-dependent process.The presence of two components for the transport, a high affinity system (Km of 3 fiM) and low affinity system (K m of 0.3-1.1 DIM), was established in both types of endothelial cells, as well as in fbroblasts (Km of 8.3 /*M and 0.8 mivi).Endothelial cells, however, could be easily differentiated from fibroblasts on the basis of several kinetic features.In the three cell types, adenosine, once taken up, was rapidly phosphorylated under the action of adenosine kinase.No evidence of adenosine deaminase activity was found in intact cells, whereas conversion of adenosine to inosine was observed in a subcellular fraction of sonicated cells.The effect of low temperatures was more marked on adenosine kinase activity than on the uptake process itself.Inosine and adenine had no effect on the transport of adenosine, whereas dipyridamole, at 10~6 M, had a very strong inhibitory action.The role of ATP and adenosine in the control of smooth muscle tone could be reexamined in view of their handling by endothelial cells of systemic and pulmonary origins.
Pleural effusion after rupture of silicone bag mammary prosthesis.
Authors: W M Stevens, J G Burdon, J F Niall
Journal: Thorax (1987)

Augmentation mammoplasty with implantation of silicone bag prostheses is commonly performed for cosmetic reasons.Despite its popularity it is associated with various complications.We describe a case of pleural effusion following the rupture of a prosthetic silicone bag, a complication that has not previously been reported. Case reportA 31 year old woman was admitted to hospital with a two week history of left sided pleuritic chest pain, which came on 24 hours after she had sustained a blow of moderate severity on the left anterior chest wall.She subsequently developed breathlessness on moderate exertion.There was no associ- ated cough, sputum production, or fever.Five years previously she had had bilateral augmentation mammo- plasties with insertion of silicone bag prostheses for cosmetic purposes.
MOPPEBVCAD Chemotherapy with Limited and Conditioned Radiotherapy in Advanced Hodgkin's Lymphoma: 10-Year Results, Late Toxicity, and Second Tumors
Authors: Paolo G. Gobbi, Chiara Broglia, Alessandro Levis, Antonio La Sala, Francesco Valentino, Teodoro Chisesi, Stefano Sacchi, Franco Corbella, Luigi Cavanna, Emilio Iannitto, Vincenzo Pavone, Stefano Molica, Gino Roberto Corazza, Massimo Federico
Journal: Clinical Cancer Research (2006)

Abstract Purpose: MOPPEBVCAD (mechlorethamine, vincristine, procarbazine, prednisone, epidoxirubicin, bleomycin, vinblastine, lomustine, doxorubicin, and vindesine) chemotherapy with limited radiotherapy was devised in 1987 to reduce late toxicity and second tumor incidence while trying to improve effectiveness through increases of dose intensity and dose density. Late results, toxicity, and second tumor incidence were reviewed in all the patients treated. Experimental Design: The drugs of three previous alternating regimens [CAD (lomustine, melphalan, and vindesine), MOPP (mechlorethamine, vincristine, procarbazine, and prednisone), and ABV (doxorubicin, bleomycin, and vinblastine)] were intensified and hybridized, the cumulative dose of mechlorethamine was lowered, and irradiation was delivered to no more than two sites either bulky or partially responding to chemotherapy. Results: A total of 307 previously untreated advanced-stage patients underwent MOPPEBVCAD chemotherapy. Radiotherapy was delivered to 118 of 307 patients (38%). Remission was complete in 290 patients (94%). With a median follow-up of 114 months, 10-year overall, disease-free, and failure-free survival rates were 79%, 84%, and 71%, respectively. Forty-two patients relapsed and 60 died. The causes of death were Hodgkin's lymphoma in 36 patients, second neoplasms in 12, cardiorespiratory diseases in 4, pulmonary diseases in 2, and unknown in 6. Sixteen second tumors (of which nine were myelodysplasia and/or acute leukemia) were diagnosed in all. Outside this series of 307 patients, MOPPEBVCAD obtained complete responses in 12 of 15 relapsed and 9 of 9 refractory patients who had previously been treated with other regimens. Conclusions: Clinical response and long-term results are very satisfactory, whereas the second tumor incidence was lower than would have been expected with MOPP analogues. Given its response/late toxicity balance, MOPPEBVCAD does not undermine the leading role of ABVD as first-line regimen but can be indicated as a very effective second-line conventional therapy.
Role of angiographic run off score as a tool to predict long term outcome following lower limb bypass surgery
Authors: Manish George, Rosie Cadwallader, Jonathan Ghosh
Journal: International Journal of Surgery (2013)

s / International Journal of Surgery 11 (2013) 686e745 740 ABSTRACTS developed a total of 9 pseudoaneurysms (6.3%:one bilateral), none of which required secondary intervention. Median pseudoaneurysm diameter was 8.4mm at diagnosis. Median follow up was 24 months. Three pseudoaneurysms had resolved at one year and a fourth by 2 years. Four patients died at a median of 15 months; none due to pseudoaneurysms. Conclusion: There is a low rate of pseudoaneurysm formation after fascial closure and no clinical impact in the mid-term. Fascial closure remains a safe and minimally invasive option. 0963: OUTCOMES FOLLOWING ARTERIAL ANGIOPLASTY IN SYMPTOMATIC INFRAPOPLITEAL DISEASE: A SYSTEMATIC REVIEW OF THE LITERATURE James Glasbey , David Bosanquet , Michael Lewis . Department of Surgery, Royal Glamorgan Hospital, Llantrisant, South Wales, UK; Cardiff University School of Medicine, Cardiff, UK. Aim: Despite a wealth of research into percutaneous intervention for arterial disease, the role of angioplasty in treating symptomatic infrapopliteal disease remains undefined. Whilst historically, surgical revascularisation has been the cornerstone of its management, angioplasty is recommended for limb salvage where open surgery is contra-indicated. Should non-inferiority be demonstrated, increasing use of endovascular techniques may reduce the morbidity associated with open surgery. This study's aims are to summarise reported outcomes in endovascular crural disease management. Methods: A systematic review of the Cochrane Library, OVID/Medline and Pubmedwas performed from 1990 to December 2012.
Intensifying Platelet Inhibition With Tirofiban in Poor Responders to Aspirin, Clopidogrel, or Both Agents Undergoing Elective Coronary Intervention
Authors: Marco Valgimigli, Gianluca Campo, Nicoletta de Cesare, Emanuele Meliga, Pascal Vranckx, Alessandro Furgieri, Dominick J. Angiolillo, Manel Sabatè, Martial Hamon, Alessandra Repetto, Salvatore Colangelo, Salvatore Brugaletta, Giovanni Parrinello, Gianfranco Percoco, Roberto Ferrari
Journal: Circulation (2009)

Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown.We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups.In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.
Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System
Authors: Steven J. Forrester, Tatsuo Kawai, Shannon O'Brien, Walter Thomas, Raymond C. Harris, Satoru Eguchi
Journal: The Annual Review of Pharmacology and Toxicology (2015)

Epidermal growth factor receptor (EGFR) activation impacts the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases including hypertension, cardiac hypertrophy, renal fibrosis, and abdominal aortic aneurysm. The capacity of G protein–coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is called transactivation and is well described, yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight recent advancements in defining the signaling cascades and downstream consequences of EGFR transactivation in the cardiovascular renal system. We also focus on studies that link EGFR transactivation to animal models of the disease, and we discuss potential therapeutic applications.
Genome-wide methylation analyses of primary human leukocyte subsets identifies functionally important cell-type–specific hypomethylated regions
Authors: Matthias Zilbauer, Tim F. Rayner, Christine Clark, Alison J. Coffey, Chris J. Joyce, Priit Palta, Aarno Palotie, Paul A. Lyons, Kenneth G. C. Smith
Journal: Blood (2013)
Gout in the Maori
Authors: G. A. Q. Lennane, B. S. Rose, I. C. Isdale
Journal: Annals of the Rheumatic Diseases (1960)

Toextend knowledge oftherheumatic diseases epidemiological studies areofconsiderable importance, andthese areofparticular interest where disease incidence indifferent racial groupsliving sidebyside canbecompared. Suchopportunity occurs inNewZealand, especially inthenorthern partoftheNorthIsland wherelive mostofthe Maoripopulation. AtRotorua inthecentre ofthis areaistheQueenElizabeth Hospital, thenational hospital forrheumatic diseases. Clinical experiences atthehospital early suggested that thepattern ofrheumatism differed inthe MaoriandEuropean populations; theMaoripeople appeared tobeaffected less byrheumatoid arthritis (Rose, 1955), butmorebyrheumatic fever andgout thantheinhabitants ofEuropean stock. These apparent differences wereconsidered worthyof further investigation notonlybecause oftheir intrinsic interest butalsobecause oftheir possible bearing onaetiological concepts ofthese diseases. Further, therateofnatural increase oftheMaori population isnowmuchgreater thanthatofthe non-Maori, andthesubject isoneofpublic health importance. Thispaperreports oneaspect ofthese investigations: theprevalence ofgoutintheMaoripopulation. Because thefindings aresomuchatvariance witha widely-held opinion that-gout ismuch commoneramongcertain races, e.g.theEnglish andGerman;itisveryuncommonamongnative races (Hunter, 1956), itisthought worthwhile torecord ourresults.
Autophagy: A Novel Mechanism of Synergistic Cytotoxicity between Doxorubicin and Roscovitine in a Sarcoma Model
Authors: Laura A. Lambert, Na Qiao, Kelly K. Hunt, Donald H. Lambert, Gordon B. Mills, Laurent Meijer, Khandan Keyomarsi
Journal: Cancer Research (2008)

Abstract Doxorubicin is a genotoxic chemotherapy agent used in treatment of a wide variety of cancers. Significant clinical side effects, including cardiac toxicity and myelosuppression, severely limit the therapeutic index of this commonly used agent and methods which improve doxorubicin efficacy could benefit many patients. Because doxorubicin cytotoxicity is cell cycle specific, the cell cycle is a rational target to enhance its efficacy. We examined the direct, cyclin-dependent kinase inhibitor roscovitine as a means of enhancing doxorubicin cytotoxicity. This study showed synergistic cytotoxicity between doxorubicin and roscovitine in three sarcoma cell lines: SW-982 (synovial sarcoma), U2OS-LC3-GFP (osteosarcoma), and SK-LMS-1 (uterine leiomyosarcoma), but not the fibroblast cell line WI38. The combined treatment of doxorubicin and roscovitine was associated with a prolonged G2-M cell cycle arrest in the three sarcoma cell lines. Using three different methods for detecting apoptosis, our results revealed that apoptotic cell death did not account for the synergistic cytotoxicity between doxorubicin and roscovitine. However, morphologic changes observed by light microscopy and increased cytoplasmic LC3-GFP puncta in U20S-LC3-GFP cells after the combined treatment suggested the induction of autophagy. Induction of autophagy was also shown in SW-982 and SK-LMS-1 cells treated with both doxorubicin and roscovitine by acridine orange staining. These results suggest a novel role of autophagy in the enhanced cytotoxicity by cell cycle inhibition after genotoxic injury in tumor cells. Further investigation of this enhanced cytotoxicity as a treatment strategy for sarcomas is warranted. [Cancer Res 2008;68(19):7966–74]
Increased risk of invasive bacterial infections in African people with sickle-cell disease: a systematic review and meta-analysis
Authors: Meenakshi Ramakrishnan, Jennifer C Moïsi, Keith P Klugman, Jesus M Feris Iglesias, Lindsay R Grant, Mireille Mpoudi-Etame, Orin S Levine
Journal: The Lancet Infectious Diseases (2010)
Research issues involving HIV-associated tuberculosis in resource-poor countries
Authors: K. M. De Cock
Journal: JAMA (1996)

Each year, there are an estimated 8 million new cases of tuberculosis (TB) and 3 million deaths due to TB, most of which occur in resource-poor countries. Tuberculosis incidence is increasing rapidly in countries with high rates of human immunodeficiency virus (HIV) infection, and despite the availability of effective interventions, many TB programs are failing to cope with the increased TB caseload. This report highlights gaps in current understanding of the interaction between TB and HIV that contribute to failure of optimal TB management and control; we focus on the diagnosis of TB, its epidemiology and transmission, preventive strategies, and programmatic issues in the integration of HIV and TB services. Research into how best to apply existing knowledge will be at least as important as searching for new knowledge. The global control of TB will also require increased resources, greater political commitment, and stronger international public health leadership.