tbuckley/cabot-search huggingface dataset:
Genome-wide Analysis of Novel Splice Variants Induced by Topoisomerase I Poisoning Shows Preferential Occurrence in Genes Encoding Splicing Factors
Authors: Stéphanie Solier, Jennifer Barb, Barry R. Zeeberg, Sudhir Varma, Mike C. Ryan, Kurt W. Kohn, John N. Weinstein, Peter J. Munson, Yves Pommier
Journal: Cancer Research (2010)

Abstract RNA splicing is required to remove introns from pre-mRNA, and alternative splicing generates protein diversity. Topoisomerase I (Top1) has been shown to be coupled with splicing by regulating serine/arginine-rich splicing proteins. Prior studies on isolated genes also showed that Top1 poisoning by camptothecin (CPT), which traps Top1 cleavage complexes (Top1cc), can alter RNA splicing. Here, we tested the effect of Top1 inhibition on splicing at the genome-wide level in human colon carcinoma HCT116 and breast carcinoma MCF7 cells. The RNA of HCT116 cells treated with CPT for various times was analyzed with ExonHit Human Splice Array. Unlike other exon array platforms, the ExonHit arrays include junction probes that allow the detection of splice variants with high sensitivity and specificity. We report that CPT treatment preferentially affects the splicing of splicing-related factors, such as RBM8A, and generates transcripts coding for inactive proteins lacking key functional domains. The splicing alterations induced by CPT are not observed with cisplatin or vinblastine and are not simply due to reduced Top1 activity, as Top1 downregulation by short interfering RNA did not alter splicing like CPT treatment. Inhibition of RNA polymerase II (Pol II) hyperphosphorylation by 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRB) blocked the splicing alteration induced by CPT, which suggests that the rapid Pol II hyperphosphorylation induced by CPT interferes with normal splicing. The preferential effect of CPT on genes encoding splicing factors may explain the abnormal splicing of a large number of genes in response to Top1cc. Cancer Res; 70(20); 8055–65. ©2010 AACR.
Sleep Apnoea in Diabetic Patients with Autonomic Neuropathy
Authors: P J Rees, J G Prior, G M Cochrane, T J H Clark
Journal: Journal of the Royal Society of Medicine (1981)

Breathing during sleep was monitored in 8 diabetic patients with objective evidence of autonomic neuropathy and in 8 diabetic patients without neuropathy. Thirty or more periods of apnoea lasting 10 seconds or longer during one night's sleep were demonstrated in 3 of the diabetic patients with autonomic neuropathy. Such apnoeic periods may be related to the high incidence of cardiorespiratory arrests reported in such patients, particularly in association with anaesthesia or pneumonia.
IL-33, an Interleukin-1-like Cytokine that Signals via the IL-1 Receptor-Related Protein ST2 and Induces T Helper Type 2-Associated Cytokines
Authors: Jochen Schmitz, Alexander Owyang, Elizabeth Oldham, Yaoli Song, Erin Murphy, Terril K. McClanahan, Gerard Zurawski, Mehrdad Moshrefi, Jinzhong Qin, Xiaoxia Li, Daniel M. Gorman, J. Fernando Bazan, Robert A. Kastelein
Journal: Immunity (2005)
Proteins Phosphorylated during Stress-induced Apoptosis Are Common Targets for Autoantibody Production in Patients with Systemic Lupus Erythematosus
Authors: Paul J. Utz, Maria Hottelet, Peter H. Schur, Paul Anderson
Journal: The Journal of Experimental Medicine (1997)

Proteins cleaved by interleukin-1β converting enzyme family proteases during apoptosis are common targets for autoantibody production in patients with systemic lupus erythematosus (SLE). We have tested the possibility that proteins phosphorylated in cells undergoing apoptosis are also targets for autoantibody production in patients with autoimmune disease. Sera from 9/12 patients containing antinuclear antibodies (10/12 meeting diagnostic criteria for SLE or a lupus overlap syndrome), precipitated new phosphoproteins from lysates derived from Jurkat T cells treated with apoptotic stimuli (i.e., Fas-ligation, gamma irradiation, ultraviolet irradiation), but not with an activation (i.e., CD3-ligation) stimulus. Sera derived from individual patients precipitated different combinations of seven distinct serine-phosphorylated proteins. None of these phosphoproteins were included in precipitates prepared using sera from patients with diseases that are not associated with autoantibody production or using serum from rheumatoid arthritis patients. Protein phosphorylation precedes, or is coincident with, the induction of DNA fragmentation, and is not observed when apoptosis is inhibited by overexpression of bcl-2. Serum from four patients precipitated a serine/threonine kinase from apoptotic cell lysates that phosphorylates proteins of 23-, 34-, and 46-kD in in vitro kinase assays. Our results suggest that proteins phosphorylated during apoptosis may be preferred targets for autoantibody production in patients with SLE.
Corticotropin-releasing hormone mRNA levels in the paraventricular nucleus of patients with Alzheimer's disease and depression
Authors: F C Raadsheer, J J van Heerikhuize, P J Lucassen, W J Hoogendijk, F J Tilders, D F Swaab
Journal: American Journal of Psychiatry (1995)

Greater activity of the hypothalamic-pituitary-adrenal (HPA) axis is associated with specific neurological and psychiatric disorders, including Alzheimer's disease and depression. Hyperactivation of paraventricular corticotropin-releasing hormone (CRH) neurons may form the basis of this increased activity of the HPA axis.Activation of the CRH neurons was determined through measurement of the amount of CRH-mRNA in the paraventricular nucleus by using quantitative, in situ hybridization histochemistry with systematically sampled frontal sections through the hypothalamus of routinely formalin-fixed and paraffin-embedded autopsy brain material of 10 comparison subjects, 10 patients with Alzheimer's disease, and seven depressed patients.CRH-mRNA levels in the paraventricular nucleus of Alzheimer's patients were markedly higher than those of comparison subjects, whereas CRH-mRNA levels in the paraventricular nucleus of depressed patients were even higher than the levels of Alzheimer's patients.Paraventricular CRH neurons in Alzheimer's disease and depression are hyperactivated, and this hyperactivation may contribute to the etiology of these disorders.
Lung water and vascular permeability-surface area in premature newborn lambs with hyaline membrane disease.
Authors: H W Sundell, T R Harris, J R Cannon, D P Lindstrom, R Green, J Rojas, K L Brigham
Journal: Circulation Research (1987)

Extravascular lung water and vascular permeability-surface area products were measured with a multiple indicator dilution method in 6 premature lambs with hyaline membrane disease 1-5 hours following delivery by cesarean section. The indicators used were 51Cr-labelled erythrocytes, 125I-albumin, 3H-water, and 14C-urea. Results were compared with previously obtained data in newborn lambs without hyaline membrane disease also delivered by cesarean section. Extravascular lung water was significantly higher in lambs with hyaline membrane disease [23.2 +/- 1.0 (SEM) vs. 10.7 +/- 1.4 ml/kg body wt]. Vascular permeability-surface area products for 14C-urea were significantly lower in lambs with hyaline membrane disease (0.30 +/- 0.10 vs 0.78 +/- 0.11 ml/s per kg). It is concluded that extravascular lung water is high in lambs with hyaline membrane disease. Permeability-surface area products for 14C-urea is low in lambs with hyaline membrane disease, which probably indicates a decrease in detectable surface area for exchange due to derecruitment or hypoperfusion of pulmonary exchange vessels in edematous and hypoxic areas of the lungs.
Tennessee's Failed Managed Care Program for Mental Health and Substance Abuse Services
Authors: Cyril F. Chang
Journal: JAMA (1998)

In July 1996, Tennessee initiated a managed mental health and substance abuse program called TennCare Partners. This publicly funded "carve-out" experiment started chaotically and soon deteriorated into a crisis. Many patients did not receive care or lost continuity of care, and the traditional "safety net" mental health system nearly disintegrated. This qualitative case study sought to ascertain the impact of the TennCare Partners program. It points out that the program's difficulties stemmed directly from a flawed design that spread funds previously earmarked for severely mentally ill patients across the entire Medicaid population. States contemplating similar reforms should strive to protect vulnerable patients by risk-adjusting capitation payments and by focusing resources on care for severely mentally ill persons. States should also minimize program complexity and ensure the accountability of managed care networks for their patients' behavioral health care needs.
Stroke Prevention in Atrial Fibrillation
Authors: Gregory Y. H. Lip, Deirdre A. Lane
Journal: JAMA (2015)

Atrial fibrillation (AF) is associated with an increase in mortality and morbidity, with a substantial increase in stroke and systemic thromboembolism. Strokes related to AF are associated with higher mortality, greater disability, longer hospital stays, and lower chance of being discharged home than strokes unrelated to AF.To provide an overview of current concepts and recent developments in stroke prevention in AF, with suggestions for practical management.A comprehensive structured literature search was performed using MEDLINE for studies published through March 11, 2015, that reported on AF and stroke, bleeding risk factors, and stroke prevention.The risk of stroke in AF is reduced by anticoagulant therapy. Thromboprophylaxis can be obtained with vitamin K antagonists (VKA, eg, warfarin) or a non-VKA oral anticoagulant (NOAC). Major guidelines emphasize the important role of oral anticoagulation (OAC) for effective stroke prevention in AF. Initially, clinicians should identify low-risk AF patients who do not require antithrombotic therapy (ie, CHA2DS2-VASc score, 0 for men; 1 for women). Subsequently, patients with at least 1 stroke risk factor (except when the only risk is being a woman) should be offered OAC. A patient's individual risk of bleeding from antithrombotic therapy should be assessed, and modifiable risk factors for bleeding should be addressed (blood pressure control, discontinuing unnecessary medications such as aspirin or nonsteroidal anti-inflammatory drugs). The international normalized ratio should be tightly controlled for patients receiving VKAs.Stroke prevention is central to the management of AF, irrespective of a rate or rhythm control strategy. Following the initial focus on identifying low-risk patients, all others with 1 or more stroke risk factors should be offered OAC.
Management of Acute Hyperparathyroidism in a Community Hospital
Authors: Nancy J. Bohannan
Journal: JAMA (1981)

Primary hyperparathyroidism is a common entity that routinely lends itself to prompt surgical cure. Infrequently, multiple surgical explorations are required to effect a cure. A case is reported of a 27-year-old man with hypercalcemia and nephrocalcinosis. The initial surgical exploration failed to identify the abnormal parathyroid tissue. Hypercalcemia necessitated rigorous antihypercalcemic therapy; three subsequent operations, including a mediastinal exploration, were unsuccessful. On the fifth exploration, which took barely an hour, a 35-g adenoma was removed from the left superior posterior mediastinum. This report illustrates that a detailed knowledge of the possible locations of aberrant parathyroid tissue and the skills of the operating surgeon are the sine qua non for those patients requiring one or more parathyroid reexplorations.
Antituberculosis Drug–induced Hepatotoxicity
Authors: JAIME R. UNGO, DENIS JONES, DAVID ASHKIN, ELENA S. HOLLENDER, DAVID BERNSTEIN, ANTHONY P. ALBANESE, ARTHUR E. PITCHENIK
Journal: American Journal of Respiratory and Critical Care Medicine (1998)

Until recently it was thought that age greater than 35 yr was the main risk factor for the development of drug-induced hepatitis (DIH) in patients receiving antituberculosis therapy. We conducted a study to determine whether infection with either the hepatitis C virus or the human immunodeficiency virus (HIV) were significant risk factors for the development of DIH in patients receiving antituberculosis therapy. Our study consisted of two parts. In the first part, 134 consecutive patients admitted for the treatment of tuberculosis (TB) were followed for the development of DIH. All of these patients were also screened for the presence of hepatitis C and HIV. In the second part of the study, those patients who were hepatitis C positive and who developed DIH on repeated reintroduction of the anti-TB drugs were offered a liver biopsy. If active inflammation, which may be suggestive of hepatitis C infection, was present on the biopsy specimen, treatment with alpha-interferon was begun and the anti-TB drugs were subsequently reintroduced. During the 18 mo of the study, 22 patients developed DIH. The relative risk of developing DIH if the patient was hepatitis C or HIV positive was fivefold and fourfold, respectively (p < 0.05). If a patient was coinfected with both hepatitis C and HIV the relative risk of developing DIH was increased 14.4-fold (p < 0.002). In the treatment part, four patients were treated with alpha-interferon, and all were able to undergo the reintroduction of anti-TB therapy without reoccurrence of DIH. Infection with hepatitis C and HIV are independent and additive risk factors for the development of DIH during TB therapy. The treatment of hepatitis C with alpha-interferon may allow the reintroduction of anti-TB agents in those who previously developed DIH when exposed to these drugs.
Fear of falling and future falls in individuals with chronic obstructive pulmonary disease
Authors: Cristino Oliveira, Annemarie Lee, Jennifer McGinley, Louis Irving, Linda Denehy
Journal: European Respiratory Journal (2014)

Background: Preliminary evidence suggests that individuals with chronic obstructive pulmonary disease (COPD) may have an increased fear of falling (FOF). The potential associations between FOF, muscle strength, postural balance, physical activity and falls, are not clear in COPD.  Aims: To compare FOF between individuals with COPD and healthy controls, determine the relationships between muscle strength, balance and FOF, and examine associations between FOF, physical activity and future falls.  Methods: FOF was assessed in 41 participants with COPD and 25 matched controls using the Falls Efficacy Scale – International (FES-I). The hand-held dynamometry, the Berg Balance Scale and the Physical Activity Scale for the Elderly were used to assess quadriceps strength, postural balance and physical activity, respectively. Falls were tracked using monthly calendars over 12 months. Pearson correlation, multiple regression and negative binomial regression were used.  Results: Participants with COPD (mean±SD; age: 71±8 years, FEV 1 : 45±16 %pred) had a higher FOF compared to controls (FES-I: 25±8 vs 20±5, p=0.01). FOF had a moderate relationship with quadriceps strength (r=-0.34, pl0.05) and postural balance (r=-0.51, pl0.05). Falls prevalence was 40%, with an incidence rate of 1.17 falls/person-year. Increased FOF was associated with lower physical activity (r=-0.37, pl0.01) and higher fall incidence rate (1.07; 95%CI: 1.01 to 1.17, p=0.01).  Conclusion: Individuals with moderate to severe COPD exhibit a higher FOF compared to healthy peers, which is related to lower muscle strength and impaired postural balance. Increased FOF is associated with lower physical activity and higher fall incidence.
Propofol sedation for flexible bronchoscopy: a randomised, noninferiority trial
Authors: Peter Grendelmeier, Michael Tamm, Eric Pflimlin, Daiana Stolz
Journal: European Respiratory Journal (2013)

Propofol has been established as a reliable method for sedation in flexible bronchoscopy. There are no data comparing propofol administered as intravenous boluses versus continuous infusion. 702 consecutive patients undergoing flexible bronchoscopy were randomly allocated to receive intravenous propofol using either an intermittent bolus technique or a continuous infusion. The primary end-point was the number of adverse events assessed at the end of flexible bronchoscopy and at 24 h. The number of any adverse event was similar in both randomised groups (219 versus 211, p=0.810). There were complications in eight cases (seven major bleedings, one respiratory failure). As compared with the bolus group, the amount of propofol required was significantly higher in the infusion group (226 ±147 mg versus 308±204.8 mg, p&lt;0.0001). In a multivariate regression model, this difference remained significant independent of the duration and the interventions performed during the procedure. The duration of bronchoscopy was significantly longer in the infusion group (median 14 (interquartile range 9–24) versus 17 (12–27) min, p&lt;0.0001). Propofol continuous infusion is as safe as bolus administration; however, it is associated with higher propofol requirements and a longer duration of the bronchoscopy.
Glomerular Endothelial Fenestrae In Vivo Are Not Formed from Caveolae
Authors: Jenny Sörensson, Wolfgang Fierlbeck, Torsten Heider, Karin Schwarz, David S Park, Peter Mundel, Michael Lisanti, Barbara J Ballermann
Journal: Journal of the American Society of Nephrology (2002)

Previous reports indicate that endothelial fenestrae in vitro can form by fusion of caveolae or caveolae-like vesicles. The principal aim of this study was to determine whether formation of glomerular endothelial cell fenestrae in vivo similarly involves caveolae and caveolin-1. Whereas caveolin-1 immunofluorescence was found around the circumference of human and mouse glomerular capillary loops, it co-localized only partially with the endothelium-specific lectin Ulex Europaeus I in human glomeruli, leaving portions of the endothelium devoid of caveolin-1. Immunogold electron microscopy, used to definitively localize caveolin-1 in glomeruli, showed that caveolin-1 was completely excluded from the fenestrated portion of the endothelium. Moreover, in caveolin-1-deficient mice, which cannot form caveolae, the ultrastructure of glomerular endothelial fenestrae appeared entirely normal. Interestingly, strong caveolin-1 immunogold labeling was observed in podocytes, where some caveolin-1 localized to filtration slits. Caveolin-1 co-immunoprecipitated with the podocyte slit diaphragm proteins nephrin and CD2AP, and dual immunofluorescence confirmed co-localization of caveolin-1 and nephrin. Nevertheless, in caveolin-1-deficient mice, podocyte ultrastructure appeared normal, and the podocyte proteins synaptopodin, nephrin, and podocin were expressed normally. In addition, blood urea nitrogen concentrations and urinary protein excretion in these mice were similar to those in wild-type mice. Thus, unlike caveolae formation, glomerular endothelial cell fenestrae formation in vivo does not require caveolin-1, ruling out the previous hypothesis that endothelial fenestrae represent fused caveolae, at least for glomerular endothelial cells. Localization of caveolin-1 to podocytes and their filtration slits is consistent with the view that the filtration slit plasma membrane represents a type of lipid raft microdomain.
Preventing Surgical-Site Infections in Nasal Carriers of<i>Staphylococcus aureus</i>
Authors: Lonneke G.M. Bode, Jan A.J.W. Kluytmans, Heiman F.L. Wertheim, Diana Bogaers, Christina M.J.E. Vandenbroucke-Grauls, Robert Roosendaal, Annet Troelstra, Adrienne T.A. Box, Andreas Voss, Ingeborg van der Tweel, Alex van Belkum, Henri A. Verbrugh, Margreet C. Vos
Journal: New England Journal of Medicine (2010)

Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism. Decolonization of nasal and extranasal sites on hospital admission may reduce this risk.In a randomized, double-blind, placebo-controlled, multicenter trial, we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction (PCR) assay, followed by treatment with mupirocin nasal ointment and chlorhexidine soap, reduces the risk of hospital-associated S. aureus infection.From October 2005 through June 2007, a total of 6771 patients were screened on admission. A total of 1270 nasal swabs from 1251 patients were positive for S. aureus. We enrolled 917 of these patients in the intention-to-treat analysis, of whom 808 (88.1%) underwent a surgical procedure. All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin. The rate of S. aureus infection was 3.4% (17 of 504 patients) in the mupirocin-chlorhexidine group, as compared with 7.7% (32 of 413 patients) in the placebo group (relative risk of infection, 0.42; 95% confidence interval [CI], 0.23 to 0.75). The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections (relative risk, 0.21; 95% CI, 0.07 to 0.62). There was no significant difference in all-cause in-hospital mortality between the two groups. The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group (P=0.005).The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission. (Current Controlled Trials number, ISRCTN56186788.)
Development of ductal carcinoma of the pancreas during follow-up of branch duct intraductal papillary mucinous neoplasm of the pancreas
Authors: H Uehara, A Nakaizumi, O Ishikawa, H Iishi, K Tatsumi, R Takakura, T Ishida, Y Takano, S Tanaka, A Takenaka
Journal: Gut (2008)

Synchronous occurrence of intraductal papillary mucinous neoplasm (IPMN) and ductal carcinoma of the pancreas has been reported. Branch duct IPMNs with lower likelihood of malignancy are not submitted to resection but are followed-up, so ductal carcinoma may develop during the follow-up. The development of ductal carcinoma of the pancreas during follow-up of branch duct IPMNs was investigated.60 patients with branch duct IPMN who had an intraductal tumour of <10 mm on imaging examinations and a negative result for malignancy on cytological examination of the pancreatic juice were investigated. They were followed-up mainly by ultrasonography (US), and additionally by endoscopic ultrasonography (EUS), CT, magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) with cytological examination of the pancreatic juice for an average period of 87 months.Ductal carcinoma of the pancreas distinct from IPMN developed in 5 of 60 (8%) branch duct IPMNs during follow-up. The 5-year rate of development of ductal carcinoma was 6.9% (95% CI 0.4% to 13.4%), the incidence of ductal carcinoma was 1.1% (95% CI 0.1% to 2.2%) per year and the standardised incidence ratio of development of ductal carcinoma was 26 (95% CI 3 to 48). Patients >70 years old developed ductal carcinoma significantly more frequently than those under 69. Four of five ductal carcinomas identified during follow-up were resectable. Cancer developed in IPMN in 2 of 60 (3%) branch duct IPMNs during follow-up.During follow-up of branch duct IPMNs, ductal carcinoma of the pancreas not infrequently developed distinct from IPMN. In the follow-up of IPMN, special attention should be paid to the development of ductal carcinoma of the pancreas.
Effects of intra-articular corticosteroids in vivo on synovial fluid variables in rheumatoid synovitis.
Authors: E J Goetzl, N E Bianco, J S Alpert, C B Sledge, P H Schur
Journal: Annals of the Rheumatic Diseases (1974)

Intra-articular corticoids in rheumatoid synovitis 63 Table I Effect of intra-articular corticosteroid on complement levels and rheumatoid factor titres in synovial fluid Intra-Number of Mean CH5o (units/mL.)Mean C4 (g.ml) Mean RF titre articular patients injection Before After Before After Before After Corticoid RF(+) 9 23 29 57