tbuckley/cabot-search huggingface dataset:
Cardiomyocyte-Specific Deletion of the Vitamin D Receptor Gene Results in Cardiac Hypertrophy
Authors: Songcang Chen, Christopher S. Law, Christopher L. Grigsby, Keith Olsen, Ting-Ting Hong, Yan Zhang, Yerem Yeghiazarians, David G. Gardner
Journal: Circulation (2011)

Background— A variety of studies carried out using either human subjects or laboratory animals suggest that vitamin D and its analogues possess important beneficial activity in the cardiovascular system. Using Cre-Lox technology we have selectively deleted the vitamin D receptor (VDR) gene in the cardiac myocyte in an effort to better understand the role of vitamin D in regulating myocyte structure and function. Methods and Results— Targeted deletion of the exon 4 coding sequence in the VDR gene resulted in an increase in myocyte size and left ventricular weight/body weight versus controls both at baseline and following a 7-day infusion of isoproterenol. There was no increase in interstitial fibrosis. These knockout mice demonstrated a reduction in end-diastolic and end-systolic volume by echocardiography, activation of the fetal gene program (ie, increased atrial natriuretic peptide and alpha skeletal actin gene expression), and increased expression of modulatory calcineurin inhibitory protein 1 (MCIP1), a direct downstream target of calcineurin/nuclear factor of activated T cell signaling. Treatment of neonatal cardiomyocytes with 1,25-dihydroxyvitamin D partially reduced isoproterenol-induced MCIP1 mRNA and protein levels and MCIP1 gene promoter activity. Conclusions— Collectively, these studies demonstrate that the vitamin D-VDR signaling system possesses direct, antihypertrophic activity in the heart. This appears to involve, at least in part, suppression of the prohypertrophic calcineurin/NFAT/MCIP1 pathway. These studies identify a potential mechanism to account for the reported beneficial effects of vitamin D in the cardiovascular system.
Catheter Ablation of Paroxysmal Atrial Fibrillation Initiated by Non–Pulmonary Vein Ectopy
Authors: Wei-Shiang Lin, Ching-Tai Tai, Ming-Hsiung Hsieh, Chin-Feng Tsai, Yung-Kuo Lin, Hsuan-Ming Tsao, Jin-Long Huang, Wen-Chung Yu, Shih-Ping Yang, Yu-An Ding, Mau-Song Chang, Shih-Ann Chen
Journal: Circulation (2003)

Background— Most of the ectopic beats initiating paroxysmal atrial fibrillation (PAF) originate from the pulmonary vein (PV). However, only limited data are available on PAF originating from the non-PV areas. Methods and Results— Two hundred forty patients with a total of 358 ectopic foci initiating PAF were included. Sixty-eight (28%) patients had AF initiated by ectopic beats (73 foci, 20%) from the non-PV areas, including the left atrial posterior free wall (28, 38.3%), superior vena cava (27, 37.0%), crista terminalis (10, 3.7%), ligament of Marshall (6, 8.2%), coronary sinus ostium (1, 1.4%), and interatrial septum (1, 1.4%). Catheter ablation eliminated AF with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively. During a follow-up period of 22±11 months, 43 patients (63.2%) were free of antiarrhythmic drugs without AF recurrence. Conclusions— Ectopic beats initiating PAF can originate from the non-PV areas, and catheter ablation of the non-PV ectopy has a moderate efficacy in treatment of PAF.
Parent misperception of control in childhood/adolescent asthma: the Room to Breathe survey
Authors: W.D. Carroll, J. Wildhaber, P.L.P. Brand
Journal: European Respiratory Journal (2011)

The aim of our study was to determine how often asthma control is achieved in children and adolescents, and how asthma affects parents' and children's daily lives. Interviews, including the childhood asthma control test (C-ACT), were conducted with 1,284 parents of asthmatic children (aged 4–15 yrs), as well as with the children themselves (aged 8–15 yrs; n=943), in Canada, Greece, Hungary, the Netherlands, South Africa and the UK. Parents reported mild asthma attacks at least weekly in 11% of children, and serious attacks (requiring oral corticosteroids or hospitalisation) at least annually in 35%. Although 73% of parents described their child's asthma as mild or intermittent, 40% of children/adolescents had C-ACT scores ≤19, indicating inadequate control, and only 14.7% achieved complete Global Initiative for Asthma (GINA)-defined control and just 9.2% achieved Scottish Intercollegiate Guidelines Network (SIGN)/British Thoracic Society (BTS)-defined control. Guideline-defined asthma control was significantly less common than well-controlled asthma using the C-ACT (p&lt;0.001). Asthma restricted the child's activities in 39% of families and caused lifestyle changes in 70%. Complete asthma control is uncommon in children worldwide. Guideline-defined control measures appear to be more stringent than those defined by C-ACT or families. Overall, parents underestimate their child's asthma severity and overestimate asthma control. This is a major potential barrier to successful asthma treatment in children.
Frequent Loss of pRb2/p130 in Human Ovarian Carcinoma
Authors: Giuseppina D’Andrilli, Valeria Masciullo, Luigi Bagella, Tiziana Tonini, Corrado Minimo, Gian Franco Zannoni, Robert L. Giuntoli, John A. Carlson, Dianne Robert Soprano, Kenneth J. Soprano, Giovanni Scambia, Antonio Giordano
Journal: Clinical Cancer Research (2004)

RB2/p130, a member of the retinoblastoma gene family, maps to human chromosome 16q12.2, a region in which deletions have been found in several human neoplasms including breast, prostatic, and ovarian carcinoma. We sought to evaluate pRb2/p130 protein expression and function in ovarian carcinoma.pRb2/p130 expression was detected by immunohistochemical and Western blot analyses in 45 primary ovarian carcinoma samples.Immunohistochemical analysis revealed loss or decrease of pRb2/p130 expression in 18 cases (40%). pRb2/p130 expression was mostly nuclear and inversely correlated to the tumor grade (P < 0.05). Western blot analysis correlated with immunohistochemical expression. Reverse transcription-PCR followed by Southern blot analysis was performed on a representative set of 20 ovarian carcinomas. RB2/p130 mRNA levels were consistent with protein expression. We found a significant increase in the percentage of G(1)-phase-arrested cells in CAOV3 and A2780 ovarian carcinoma cell lines after transduction with an adenovirus carrying the RB2/p130 gene (Ad-CMV-RB2/p130).These data indicate that loss or decrease of pRb2/p130 expression is a frequent event in ovarian carcinoma and is regulated mostly at the transcriptional level. Moreover, pRb2/p130 overexpression is able to arrest cell growth in ovarian carcinoma cells, suggesting the putative role of pRb2/p130 as a tumor suppressor in this malignancy.
Value of a second freeze-thaw cycle in cryotherapy of common warts
Authors: J. BERTH-JONES, J. BOURKE, H. EGLITIS, C. HARPER, P. KIRK, S. PAVORD, R. RAJAPAKSE, P. WESTON, T. WIGGINS, P.E. HUTCHINSON
Journal: British Journal of Dermatology (1994)

Journal Article Value of a second freeze‐thaw cycle in cryotherapy of common warts Get access J. BERTH‐JONES, J. BERTH‐JONES Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Dr John Berth‐Jones, Consultant Dermatologist, Walsgrave Hospital, Clifford Bridge Road, Walsgrave, Coventry, War. CV2 2DX, U.K. Search for other works by this author on: Oxford Academic Google Scholar J. BOURKE, J. BOURKE Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar H. EGLITIS, H. EGLITIS Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. HARPER, C. HARPER Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. KIRK, P. KIRK Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar S. PAVORD, S. PAVORD Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar R. RAJAPAKSE, R. RAJAPAKSE Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar P. WESTON, P. WESTON Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar T. WIGGINS, T. WIGGINS Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar P.E. HUTCHINSON P.E. HUTCHINSON Department of Dermatology, Leicester Royal Infirmary, Leicester LE1 5WW, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 6, 1 December 1994, Pages 883–886, https://doi.org/10.1111/j.1365-2133.1994.tb08594.x Published: 01 December 1994 Article history Accepted: 21 March 1994 Published: 01 December 1994
High-Dose Melphalan and Autologous Stem-Cell Transplantation in Patients with AL Amyloidosis: An 8-Year Study
Authors: Martha Skinner, Vaishali Sanchorawala, David C. Seldin, Laura M. Dember, Rodney H. Falk, John L. Berk, Jennifer J. Anderson, Carl O'Hara, Kathleen T. Finn, Caryn A. Libbey, Janice Wiesman, Karen Quillen, Niall Swan, Daniel G. Wright
Journal: Annals of Internal Medicine (2004)

AL amyloidosis is a fatal disease resulting from tissue deposition of amyloid fibrils derived from monoclonal immunoglobulin light chains. Treatment with oral chemotherapy is minimally effective.To test survival and organ response in a large sample of patients treated with high-dose intravenous melphalan (100 to 200 mg/m2) and autologous blood stem-cell transplantation.8-year longitudinal analysis of clinical effectiveness.University-affiliated specialty referral clinic.701 consecutive new patients with AL amyloidosis.High-dose chemotherapy and autologous stem-cell transplantation for patients who met eligibility requirements based on organ involvement and clinical status.Survival analysis of all patients evaluated and a detailed analysis of treatment outcome in the subgroup that received high-dose melphalan and stem-cell transplantation.Among 701 patients with AL amyloidosis, 394 (56%) were eligible for high-dose melphalan and stem-cell transplantation; 82 did not proceed with treatment because of patient choice or disease progression. Median survival of the 312 patients who initiated treatment was 4.6 years. A complete hematologic response, defined as no evidence of an underlying plasma cell dyscrasia 1 year after treatment, was achieved in 40% of patients and was associated with prolonged survival. Statistically significant improvements occurred in end-organ disease and were greater in patients with a complete hematologic response. Mortality rate within 100 days of treatment with high-dose melphalan and stem-cell transplantation was 13%; patients with cardiomyopathy had the highest mortality rates.Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.
Interleukin 1 stimulates its own receptor expression on human fibroblasts through the endogenous production of prostaglandin(s).
Authors: T Akahoshi, J J Oppenheim, K Matsushima
Journal: Journal of Clinical Investigation (1988)

The regulation of interleukin 1 receptor (IL 1R) expression on human dermal fibroblasts was investigated. On exposure to IL 1 for 3 h at 37 degrees C, the capacity of fibroblasts to bind 125I-labeled human recombinant IL 1 alpha (125I-IL 1 alpha) was reduced by 75%. The IL 1 binding capability of the fibroblasts was restored to control levels by 16 h after removal of unbound IL 1, and then increased to about twofold over that of control cells by 48 h. This later enhancement of IL 1 receptor expression after IL 1 treatment was abolished by indomethacin. Addition of exogenous (PGE1 and PGE2, also analogues of AMP, or forskolin increased the specific binding of 125I-IL 1 alpha to fibroblasts. Scatchard analysis indicated that PGE2 increased the number of IL 1R from approximately 1.6 X 10(3) to 5.4 X 10(3) per cell without change in the binding affinity. These data suggest that the later IL 1-induced up-regulation of IL 1R is mediated by IL 1 stimulation of endogenous prostaglandin production. The combination of PGE2 and prednisolone increased the number of IL 1R on fibroblasts in an additive manner.
Disseminated lung cancer or extragonadal germ cell tumour?
Authors: E Wouters, J Van Meerbeeck, L Dirix, M Janssen, E Van Marck, P Vermeire, A Van Oosterom
Journal: European Respiratory Journal (1991)

Two patients are reported in whom an initial diagnosis of disseminated non small cell bronchogenic carcinoma was subsequently changed into a final diagnosis of extragonadal germ cell tumour. The clinical importance of the differential diagnosis between these two malignancies is highlighted and the management of extragonadal germ cell tumours is discussed.
Long-term outcomes after stenting versus endarterectomy for treatment of symptomatic carotid stenosis: the International Carotid Stenting Study (ICSS) randomised trial
Authors: Leo H Bonati, Joanna Dobson, Roland L Featherstone, Jörg Ederle, H Bart van der Worp, Gert J de Borst, Willem P Th M Mali, Jonathan D Beard, Trevor Cleveland, Stefan T Engelter, Philippe A Lyrer, Gary A Ford, Paul J Dorman, Martin M Brown
Journal: The Lancet (2014)

Stenting is an alternative to endarterectomy for treatment of carotid artery stenosis, but long-term efficacy is uncertain. We report long-term data from the randomised International Carotid Stenting Study comparison of these treatments.Patients with symptomatic carotid stenosis were randomly assigned 1:1 to open treatment with stenting or endarterectomy at 50 centres worldwide. Randomisation was computer generated centrally and allocated by telephone call or fax. Major outcomes were assessed by an independent endpoint committee unaware of treatment assignment. The primary endpoint was fatal or disabling stroke in any territory after randomisation to the end of follow-up. Analysis was by intention to treat ([ITT] all patients) and per protocol from 31 days after treatment (all patients in whom assigned treatment was completed). Functional ability was rated with the modified Rankin scale. This study is registered, number ISRCTN25337470.1713 patients were assigned to stenting (n=855) or endarterectomy (n=858) and followed up for a median of 4·2 years (IQR 3·0-5·2, maximum 10·0). Three patients withdrew immediately and, therefore, the ITT population comprised 1710 patients. The number of fatal or disabling strokes (52 vs 49) and cumulative 5-year risk did not differ significantly between the stenting and endarterectomy groups (6·4% vs 6·5%; hazard ratio [HR] 1·06, 95% CI 0·72-1·57, p=0·77). Any stroke was more frequent in the stenting group than in the endarterectomy group (119 vs 72 events; ITT population, 5-year cumulative risk 15·2% vs 9·4%, HR 1·71, 95% CI 1·28-2·30, p<0·001; per-protocol population, 5-year cumulative risk 8·9% vs 5·8%, 1·53, 1·02-2·31, p=0·04), but were mainly non-disabling strokes. The distribution of modified Rankin scale scores at 1 year, 5 years, or final follow-up did not differ significantly between treatment groups.Long-term functional outcome and risk of fatal or disabling stroke are similar for stenting and endarterectomy for symptomatic carotid stenosis.Medical Research Council, Stroke Association, Sanofi-Synthélabo, European Union.
Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011
Authors: M.-H. Tsai, S.-H. Wang, J.-F. Hsu, L.-C. Lin, S.-M. Chu, H.-R. Huang, M.-C. Chiang, R.-H. Fu, J.-J. Lu, Y.-C. Huang
Journal: Clinical Microbiology and Infection (2015)
Effect of dietary sodium on airways responsiveness and its importance in the epidemiology of asthma: an evaluation in three areas of northern England.
Authors: G Devereux, J R Beach, C Bromly, A J Avery, S M Ayatollahi, S M Williams, S C Stenton, S J Bourke, D J Hendrick
Journal: Thorax (1995)

BACKGROUND--Although several investigations have shown a relationship between asthma (or its surrogate, airways responsiveness) and dietary or urinary sodium, others have not, and the matter remains controversial. This "salt effect" has been investigated during two recent epidemiological surveys of men in northern England. The first assessed the possible effect on airways responsiveness of occupational exposure to welding fumes, and the second characterised airways responsiveness in two geographically distinct residential areas. Thus, three separate study areas/populations were involved. METHODS--Investigation 1 involved 1059 shipyard workers aged 16-27 years who were exposed variously to welding fumes, and Investigation 2 involved 587 men aged 20-44 years who lived in rural West Cumbria or in urban Newcastle upon Tyne. In Investigation 1, a 24 hour urine specimen was requested from each subject with quantifiable airways responsiveness (PD20 &lt; or = 6400 micrograms methacholine) and from an equal number of subjects without measurable airways responsiveness from the same occupational subgroup. In Investigation 2, every subject was asked to provide a 24 hour urine specimen. RESULTS--Of the men undergoing methacholine tests, satisfactory 24 hour urine specimens were obtained from 234 (22.1%) in Investigation 1 and 232 (39.5%) in Investigation 2. Analysis using multiple linear regression, multiple linear logistic regression, and multiple regression for censored data produced consistent results within each study population but conflicting results between them, such that there was no hint of a relationship between airways responsiveness and 24 hour urinary sodium excretion in the shipyard workers of Investigation 1 nor in the rural West Cumbrian population of Investigation 2, but an association was found in the urban Newcastle population of Investigation 2. All study populations were sufficiently large to demonstrate anticipated relationships between airways responsiveness and atopy, baseline FEV1, and (Newcastle only) age. CONCLUSIONS--If airways responsiveness is related to dietary sodium the relationship is not likely to be strong.
Relationship between FLT3 mutation status, biologic characteristics, and response to targeted therapy in acute promyelocytic leukemia
Authors: Rosemary E. Gale, Robert Hills, Arnold R. Pizzey, Panagiotis D. Kottaridis, David Swirsky, Amanda F. Gilkes, Elizabeth Nugent, Kenneth I. Mills, Keith Wheatley, Ellen Solomon, Alan K. Burnett, David C. Linch, David Grimwade
Journal: Blood (2005)
Management of Immune-Related Adverse Events and Kinetics of Response With Ipilimumab
Authors: Jeffrey S. Weber, Katharina C. Kähler, Axel Hauschild
Journal: Journal of Clinical Oncology (2012)

Monoclonal antibodies directed against the immune checkpoint protein cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152)-ipilimumab and tremelimumab-have been investigated in metastatic melanoma and other cancers and have shown promising results. Recently, ipilimumab was approved by the US Food and Drug Administration for the treatment of metastatic melanoma. We review the literature on managing the adverse effects and kinetics of tumor regression with ipilimumab and provide guidelines on their management. During treatment with these antibodies, a unique set of adverse effects may occur, called immune-related adverse events (irAEs). These include rashes, which may rarely progress to life-threatening toxic epidermal necrolysis, and colitis, characterized by a mild to moderate, but occasionally also severe and persistent diarrhea. Hypophysitis, hepatitis, pancreatitis, iridocyclitis, lymphadenopathy, neuropathies, and nephritis have also been reported with ipilimumab. Early recognition of irAEs and initiation of treatment are critical to reduce the risk of sequelae. Interestingly, irAEs correlated with treatment response in some studies. Unique kinetics of response have been observed with CTLA-4 blockade with at least four patterns: (1) response in baseline lesions by week 12, with no new lesions seen; (2) stable disease, followed by a slow, steady decline in total tumor burden; (3) regression of tumor after initial increase in total tumor burden; and (4) reduction in total tumor burden during or after the appearance of new lesion(s) after week 12. We provide a detailed description of irAEs and recommendations for practicing oncologists who are managing them, along with the unusual kinetics of response associated with ipilimumab therapy.
CY15, a Malignant Histiocytic Tumor That Is Phenotypically Similar to Immature Dendritic Cells
Authors: Thomas Kammertoens, Ralf Willebrand, Bettina Erdmann, Liangping Li, Yongping Li, Boris Engels, Wolfgang Uckert, Thomas Blankenstein
Journal: Cancer Research (2005)

Abstract The origin and pathogenesis of histiocytic malignancies and the biology of the tumor cells are poorly understood. We have isolated a murine histiocytic tumor cell line (CY15) from a BALB/c IFNγ−/− mouse and characterized it in terms of phenotype and function. The morphology, as judged by electron microscopy, and the surface marker phenotype suggests that CY15 cells are similar to immature dendritic cells (CD11c low, MHC II low, CD11b+, B7.1+, B7.2+, and CD40+). The cells form tumors in BALB/c mice and metastasize to spleen, liver, lung, kidney, and to a lesser extend to lymph nodes and bone marrow, as judged by the growth of green fluorescent protein transfected tumor cells in mice. CY15 cells are capable of actively taking up antigen (FITC-ovalbumin) and can stimulate T lymphocytes in an allogenic mixed lymphocyte reaction but less effectively than their normal counterparts (immature dendritic cells). They respond to interleukin 4 (IL-4) with up-regulation of CD11c. If stimulated with IFNγ the cells up-regulate MHC II, CD40 B7.1, and B7.2. Lipopolysaccharide induces the cells to up-regulate B7.1 and B7.2 and to secrete tumor necrosis factor α and IL-12. Based on these data, CY15 is a dendritic cell–like tumor cell line and may serve as a transplantable tumor model for histiocytosis in humans.
Discrepancy Between Postnatal and Antenatal Management of Gestational Diabetes in the U.K.
Authors: Fahmy W.F. Hanna, John R. Peters, Joan Harlow, Peter W. Jones
Journal: Diabetes Care (2007)

There has been no consensus for screening methodology, diagnosis, and management of gestational diabetes mellitus (GDM). We aimed to evaluate routine practice for GDM management across the U.K., including postnatal care. Questionnaires were sent to all members of the Association of British Clinical Diabetologists. They were asked to describe how patients were screened for GDM, the diagnostic criteria, and subsequent management and clinical targets, as well as postnatal care. Centers that did not initially respond were followed up by personal communication. Regional variability trends were assessed by subdividing the U.K. into 10 regions and then analyzing the data with the StatXact χ2 test (version …