tbuckley/cabot-search huggingface dataset:
Fourth annual North American and 1990 International Cystic Fibrosis Conference.
Authors: J. S. Elborn
Journal: Thorax (1991)

The discovery of the cystic fibrosis gene over a year ago has resulted in intensive research to identify all the mutations that cause this disease, to investigate the potential of gene therapy, and to determine the exact nature and function of the normal gene product.Many of the advances since the discovery of the gene were described at the Fourth North American and 1990 International Cystic Fibrosis Conference in Washington DC in October to an audience of over 2000, including 20 clinicians and scientists from Eastern Europe.The emphasis of the meeting was on developments in molecular and cell biology in relation to cystic fibrosis, but there was also much to interest clinical and paramedical staff concerned with the care of patients with cystic fibrosis.The proceedings of the meeting are published as supplement 5 (1990) in Pediatric Pulmonology.
Simplifying IDSA/ATS pneumonia guidelines
Authors: Waleed Salih, James Chalmers, Stuart Schembri
Journal: European Respiratory Journal (2013)

Introduction  The aim of this study was to determine if the 2007 IDSA/ATS minor criteria for severe community-acquired pneumonia (CAP) could be simplified by removing non-contributory variables.  Methods  The components of the minor criteria were validated using a systematic review and meta-analysis of 7 studies. Odds ratios were pooled using a random effects model. Variables that occurred in   Results  All variables were significantly associated with mortality and ICU admission but leukopaenia(  A simplified score excluding these variables performed similarly for prediction of mortality AUC 0.77 95% CI 0.73-0.81 vs 0.78(0.74-0.82), p=0.9 and ICU admission AUC 0.85(0.82-0.87) vs 0.85(0.82-0.88), p=0.9 in the prospective cohort. Additional predictors suggested by the IDSA/ATS including hypo/hyperglycaemia, acidosis, liver cirrhosis, acute alcohol ingestion or alcohol withdrawal and asplenia were associated with mortality and ICU admission,but only incorporating pH  Conclusions  The IDSA/ATS minor criteria can be simplified by removing 3 infrequent variables without affecting prognostic accuracy.
Effect of cysteamine on gastroduodenal mucosal histamine in rat.
Authors: S Boesby, W K Man, R Mendez-Diaz, J Spencer
Journal: Gut (1983)

Cysteamine administration to rats is followed by a high incidence of peptic ulceration. The aim of the present study was to investigate the effect of cysteamine on gastric and duodenal mucosal histamine and gastric mucosal histamine formation capacity. After a four hour fast, cysteamine in doses of 50, 100, 200, 300, 400, and 500 mg/kg bodyweight was injected subcutaneously to male Wistar rats; saline injection was used as control. After 24 hours the animals were killed; the stomach and duodenum were removed and examined for ulceration. Mucosal biopsies were taken for histamine studies. Gastric and duodenal ulceration tended to appear with increasing incidence with higher doses. A direct correlation was found between the dose of cysteamine and gastric mucosal histamine (p less than 0.02), and duodenal mucosal histamine (p less than 0.05). Further, a direct relationship was found between gastric mucosal histidine decarboxylase activity and the dose of cysteamine (p less than 0.05). Gastric mucosal histamine and histidine decarboxylase activity showed a direct correlation (p less than 0.001). Gastric and duodenal mucosal histamine and gastric mucosal histamine formation capacity were higher in rats with ulcers than in controls and rats without ulcers. In rat, cysteamine induces dose related changes in mucosal histamine and histidine decarboxylase activity. These changes are related to ulcer formation; histamine may be involved in the pathophysiology of cysteamine induced ulcer formation.
Recurrent mutation of the ID3 gene in Burkitt lymphoma identified by integrated genome, exome and transcriptome sequencing
Authors: Julia Richter, Matthias Schlesner, Steve Hoffmann, Markus Kreuz, Ellen Leich, Birgit Burkhardt, Maciej Rosolowski, Ole Ammerpohl, Rabea Wagener, Stephan H Bernhart, Dido Lenze, Monika Szczepanowski, Maren Paulsen, Simone Lipinski, Robert B Russell, Sabine Adam-Klages, Gordana Apic, Alexander Claviez, Dirk Hasenclever, Volker Hovestadt, Nadine Hornig, Jan O Korbel, Dieter Kube, David Langenberger, Chris Lawerenz, Jasmin Lisfeld, Katharina Meyer, Simone Picelli, Jordan Pischimarov, Bernhard Radlwimmer, Tobias Rausch, Marius Rohde, Markus Schilhabel, René Scholtysik, Rainer Spang, Heiko Trautmann, Thorsten Zenz, Arndt Borkhardt, Hans G Drexler, Peter Möller, Roderick A F MacLeod, Christiane Pott, Stefan Schreiber, Lorenz Trümper, Markus Loeffler, Peter F Stadler, Peter Lichter, Roland Eils, Ralf Küppers, Michael Hummel, Wolfram Klapper, Philip Rosenstiel, Andreas Rosenwald, Benedikt Brors, Reiner Siebert
Journal: Nature Genetics (2012)
Thrombin stimulates proliferation of cultured rat aortic smooth muscle cells by a proteolytically activated receptor.
Authors: C A McNamara, I J Sarembock, L W Gimple, J W Fenton, S R Coughlin, G K Owens
Journal: Journal of Clinical Investigation (1993)

Thrombin has been implicated in the stimulation of smooth muscle cell (SMC) proliferation that contributes to post angioplasty restenosis. The present studies demonstrated that human alpha-thrombin was a potent and efficacious mitogen for cultured rat aortic SMC, stimulating an increase in 3H-thymidine incorporation, as well as an increase in cell number at 1 to 10 nM concentration. gamma-Thrombin, which is enzymatically active but lacks fibrinogen clotting activity, stimulated SMC mitogenesis but was approximately 10-fold less potent than alpha-thrombin. In contrast, D-phenylalanyl-L-propyl-L-arginyl-chloromethyl ketone-alpha-thrombin, which lacked enzymatic activity, had no mitogenic effect. Diisopropylfluorophosphate-alpha-thrombin failed to stimulate mitogenesis except at concentrations having equivalent enzymatic activity as that of alpha-thrombin at its threshold for mitogenesis. Thus, thrombin-induced proliferation was dependent on enzymatic activity. A 14-residue peptide (SFLLRNPNDKYEPF) corresponding to amino acids 42 through 55 of the human thrombin receptor (Vu, T. K., D. T. Hung, V. I. Wheaton, and S. R. Coughlin, 1991. Cell. 64:1057-1068) had full efficacy in stimulating SMC proliferation. Reversing the first two amino acids of this peptide abolished mitogenic activity. Northern analysis demonstrated that SMC expressed a single mRNA species that hybridized to a labeled thrombin receptor cDNA probe. These findings indicate that alpha-thrombin stimulates SMC proliferation via the proteolytic activation of a receptor very similar or identical to that previously identified.
Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells
Authors: Hooi Ching Lim, Hinke AB Multhaupt, John R Couchman
Journal: Molecular Cancer (2015)

Cell surface proteoglycans interact with numerous regulators of cell behavior through their glycosaminoglycan chains. The syndecan family of transmembrane proteoglycans are virtually ubiquitous cell surface receptors that are implicated in the progression of some tumors, including breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved.The MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry, invasion and collagen degradation assays. Selected receptors including PAR-1 and syndecans were depleted by siRNA treatments to assess cell morphology and behavior. Immunohistochemistry for syndecan-2 and its interacting partner, caveolin-2 was performed on human breast tumor tissue arrays. Two-tailed paired t-test and one-way ANOVA with Tukey's post-hoc test were used in the analysis of data.MDA-MB231 cells were shown to be highly sensitive to exogenous heparan sulfate or heparin, promoting increased spreading, focal adhesion and adherens junction formation with concomitantly reduced invasion and matrix degradation. The molecular basis for this effect was revealed to have two components. First, thrombin inhibition contributed to enhanced cell adhesion and reduced invasion. Second, a specific loss of cell surface syndecan-2 was noted. The ensuing junction formation was dependent on syndecan-4, whose role in promoting actin cytoskeletal organization is known. Syndecan-2 interacts with, and may regulate, caveolin-2. Depletion of either molecule had the same adhesion-promoting influence, along with reduced invasion, confirming a role for this complex in maintaining the invasive phenotype of mammary carcinoma cells. Finally, both syndecan-2 and caveolin-2 were upregulated in tissue arrays from breast cancer patients compared to normal mammary tissue. Moreover their expression levels were correlated in triple negative breast cancers.Cell surface proteoglycans, notably syndecan-2, may be important regulators of breast carcinoma progression through regulation of cytoskeleton, cell adhesion and invasion.
Refractory hypoxemia during liver cirrhosis. Hepatopulmonary syndrome or "primary" pulmonary hypertension?
Authors: O Raffy, C Sleiman, F Vachiery, H Mal, C Roue, A Hadengue, G Jebrak, M Fournier, R Pariente
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

We report an uncommon mechanism of severe hypoxemia in two cirrhotic patients under long-term beta-blocker therapy. Our patients presented with profound hypoxemia refractory to oxygen therapy, normal lung radiography and pulmonary function tests, and evidence of right-to-left anatomic shunt. Although these features are highly suggestive of hepatopulmonary syndrome, pulmonary hypertension was present, and a right-to-left shunt through a patent foramen ovale was demonstrated by contrast-enhanced echocardiography. No cause of pulmonary hypertension other than portal hypertension was identified. Pulmonary hypertension and intracardiac right-to-left shunt eventually regressed after discontinuation of beta-blocker therapy. We conclude that "primary" pulmonary hypertension associated with portal hypertension may because of severe hypoxemia during liver cirrhosis. Differential diagnosis of hepatopulmonary syndrome relies upon contrast-enhanced echocardiography and may be of critical importance because of possible therapeutic implications.
P228 Impact of long-acting bronchodilator therapy on mortality in copd: a real-life retrospective cohort study: Abstract P228 Table 1.
Authors: A Manoharan, PM Short, WJ Anderson, BJ Lipworth
Journal: Thorax (2013)

<h3>Introduction and Objectives</h3> Long-acting muscarinic antagonists (LAMA) and long-acting beta-agonists (LABA) are first-line treatments for COPD. The addition of inhaled corticosteroids (ICS) is recommended for patients with frequent exacerbations who are not adequately controlled with long-acting bronchodilators. These medications have been largely evaluated independently in placebo controlled randomised trials. In this ‘real-life’ study we investigated the impact of these medications used independently and in combination on mortality. <h3>Methods</h3> We conducted a retrospective cohort study using data from patients with a diagnosis of COPD in NHS Tayside between 2001 and 2010. All-cause and cardiovascular mortality was assessed using Cox proportional hazard regression after adjustment for FEV<sub>1</sub>, age, sex, smoking pack-years, oxygen saturation, cardiovascular and respiratory admissions; cardiovascular medications and diabetes. Patients on short-acting bronchodilators only were used as the controls. <h3>Results</h3> A total of 5048 patients were included in the study with mean age at diagnosis of 69.4 years and mean follow-up of 4.0 years. 623 were on long-acting bronchodilators only, 3510 on long-acting bronchodilator and ICS; and 915 controls. Crude hazard ratios are shown in Table 1. Adjusted HR (95%CI) for all-cause mortality for LABA only, LAMA only; and LABA + LAMA were 0.70 (0.45–1.09), 0.52 (0.37–0.73) and 0.53 (0.34–0.84) respectively. Adjusted HR for all-cause mortality for LABA + ICS, LAMA + ICS; LABA + LAMA + ICS were 0.56 (0.45 – 0.70), 0.34 (0.25 – 0.47) and 0.29 (0.24 – 0.36) respectively. Adjusted HR for cardiovascular mortality for LABA only, LAMA only; and LABA + LAMA were 0.63 (0.28–1.44), 0.41 (0.21 – 0.79) and 0.39 (0.17 – 0.90) respectively, and for LABA + ICS, LAMA + ICS; LABA + LAMA + ICS were 0.50 (0.33 – 0.75), 0.23 (0.12 – 0.45) and 0.22 (0.15 – 0.33) respectively. <h3>Conclusions</h3> LABA monotherapy does not confer any mortality benefit but when used in combination with ICS reduces both all-cause and cardiovascular mortality. In contrast, LAMA whether given alone or in combination with a LABA and /or ICS reduces both all-cause and cardiovascular mortality. This ‘real-life’ study suggests that LABA should perhaps not be given as monotherapy but only in conjunction with a LAMA or ICS.
Monitoring Cerebral Blood Flow, Oxygen, and Glucose Metabolism
Authors: JOHN S. MEYER, F. GOTOH, M. AKIYAMA, S. YOSHITAKE
Journal: Circulation (1967)

More accurate methods for monitoring cerebral blood flow, oxygen, and glucose metabolism with results of their application in human volunteers are described. Subjects with various types of cerebral vascular disease showed decreased cerebral blood flow and oxygen and glucose metabolism but anaerobic glycolysis appeared to be increased. Inhalation of 100% oxygen decreased anaerobic glycolysis, and mixtures of oxygen, 5% CO 2 plus oxygen, 5% CO 2 plus air, and hyperventilation all showed that cerebral vascular reactivity is reduced in cerebrovascular disease. Nevertheless, inhalation of 5% mixtures of CO 2 in air or oxygen significantly increased cerebral blood flow. Inhalation of 5% CO 2 plus oxygen significantly increased cerebral oxygen consumption in cerebrovascular disease within 10 minutes of its institution. The depression of cerebral glucose metabolism and oxygen consumption appears to be amenable to rapid improvement in some subjects with stroke. Intravenous administration of nylidrin hydrochloride decreased cerebral vascular resistance but did not increase cerebral blood flow or metabolism, presumably by autoregulation. Intravenous injection of 100 ml of low molecular-weight dextran increased cerebral blood flow and oxygen consumption but not to the level of statistical significance. A case of brain-stem ischemia showed a large increase of cerebral blood flow, oxygen metabolism, and glucose consumption after surgical reconstruction of the left vertebral artery accompanied by clinical recovery.
Targeting Mitochondria for Neuroprotection in Parkinson Disease
Authors: Anthony H. V. Schapira, Sandip Patel
Journal: JAMA Neurology (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Neurology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Neurology journal
Intestinal reticulosis as a complication of idiopathic steatorrhoea
Authors: K. R. Gough, A. E. Read, J. M. Naish
Journal: Gut (1962)

Three patients who had idiopathic steatorrhoea associated with reticulosarcoma of either the jejunum or the ileum are described. Previously reported cases with these features are reviewed and the suggestion is made that the reticulosis may arise as a complication of idiopathic steatorrhoea.
Low‐dose ARA‐C consistently induces hematologic responses in the clinical 5q–syndrome
Authors: Harinder S. Juneja, Madhu Jodhani, Frank H. Gardner, David Trevarthen, Margaret Schottstedt
Journal: American Journal of Hematology (1994)

Abstract Five patients with the classical clinical syndrome associated with a deletion of the long arm of chromosome 5, i.e., anemia, macrocytosis, and thrombocytosis, or a normal platelet count, were treated successfully with subcutaneous low‐dose cytosine arabinoside (LDARA‐C). Prior therapy with other drugs had failed in four of the five patients. A total of nine complete and one partial hematologic responses were induced in five patients. Duration of the first hematologic response ranged from 3 to 30+ months. Two patients (cases 3 and 4) continue in their first hematologic response at 29 and 30 months. Upon relapse, up to three responses could be reinduced in two patients. Duration of the subsequent hematologic responses in case 1 was 16, 8, and 10 months and case 2 achieved two responses of 15 and 18+ months duration. LDARA‐C therapy was associated with mild to severe neutropenia and moderate to severe thrombocytopenia. Thus, subcutaneous LDARA‐C is highly effective in the treatment of patients with myelodysplasia associated with deletion of the long– arm of chromosome 5 (5q–). © 1994 Wiley‐Liss, Inc.
Epithelial cells disseminate into the bone marrow of colorectal adenoma patients
Authors: R Steinert
Journal: Gut (2005)

Although the skeleton is not a preferred site of overt metastasis in colorectal cancer, demonstration of tumour cells in bone marrow has to be seen as evidence of the general disseminative capability of an individual tumour.1 Other observations such as involuntary transmission of tumour by organ grafts directly supports the notion that very few quiescent cells lodging at improbable sites, such as the kidney or heart, suffice to generate de novo metastatic disease in the organ recipient.2 The TNM classification recommends mention of the presence of disseminated tumour cells as a facultative factor for metastatisation (M0 (i+) or M0 (mol+)) according to the immunological or molecular detection technique.3

However, the results …
Calcineurin inhibitors in bronchiolitis obliterans syndrome following stem cell transplantation
Authors: Katrin E. Hostettler, Jörg P. Halter, Sabine Gerull, Didier Lardinois, Spasenija Savic, Michael Roth, Michael Tamm
Journal: European Respiratory Journal (2013)

Bronchiolitis obliterans is a complication after allogeneic haematopoietic stem cell transplantation (HSCT). Management of bronchiolitis obliterans comprises intensive immunosuppression, but treatment response is poor. We investigated the effect of cyclosporine A (CsA), tacrolimus (FK506), methylprednisolone (mPRED), mycophenolate mofetil (MMF) and everolimus on the proliferation of primary lung myofibroblasts from HSCT patients with bronchiolitis obliterans syndrome (BOS). Cells were isolated from surgical lung biopsies of eight HSCT patients with BOS. Proliferation was assessed by [(3)H]-thymidine incorporation. Biopsies revealed constrictive bronchiolitis obliterans in three patients and lymphocytic bronchiolitis in five patients. CsA and FK506 significantly induced proliferation of myofibroblasts. mPRED and MMF caused a significant inhibition of proliferation, whereas everolimus had no effect. Costimulation with FK506, mPRED and MMF significantly inhibited proliferation. Serial pulmonary function tests over 12 months after lung biopsy and under triple therapy demonstrated that patients with lymphocytic bronchiolitis had a significant improvement in forced expiratory volume in 1 s (FEV1), whereas FEV1 of patients with bronchiolitis obliterans was unchanged. Our data demonstrate a pro-proliferative effect of calcineurin inhibitors on primary human lung myofibroblasts obtained from patients with BOS after HSCT. In contrast, based on the observed antiproliferative capacity of MMF in vitro, MMF-based calcineurin inhibitor-free treatment strategies should be further evaluated in patients with bronchiolitis obliterans after HSCT.
Religious Coping and Use of Intensive Life-Prolonging Care Near Death in Patients With Advanced Cancer
Authors: Andrea C. Phelps
Journal: JAMA (2009)

<h3>Context</h3>Patients frequently rely on religious faith to cope with cancer, but little is known about the associations between religious coping and the use of intensive life-prolonging care at the end of life.<h3>Objective</h3>To determine the way religious coping relates to the use of intensive life-prolonging end-of-life care among patients with advanced cancer.<h3>Design, Setting, and Participants</h3>A US multisite, prospective, longitudinal cohort of 345 patients with advanced cancer, who were enrolled between January 1, 2003, and August 31, 2007. The Brief RCOPE assessed positive religious coping. Baseline interviews assessed psychosocial and religious/spiritual measures, advance care planning, and end-of-life treatment preferences. Patients were followed up until death, a median of 122 days after baseline assessment.<h3>Main Outcome Measures</h3>Intensive life-prolonging care, defined as receipt of mechanical ventilation or resuscitation in the last week of life. Analyses were adjusted for demographic factors significantly associated with positive religious coping and any end-of-life outcome at P &lt; .05 (ie, age and race/ethnicity). The main outcome was further adjusted for potential psychosocial confounders (eg, other coping styles, terminal illness acknowledgment, spiritual support, preference for heroics, and advance care planning).<h3>Results</h3>A high level of positive religious coping at baseline was significantly associated with receipt of mechanical ventilation compared with patients with a low level (11.3% vs 3.6%; adjusted odds ratio [AOR], 2.81 [95% confidence interval {CI}, 1.03-7.69]; P = .04) and intensive life-prolonging care during the last week of life (13.6% vs 4.2%; AOR, 2.90 [95% CI, 1.14-7.35]; P = .03) after adjusting for age and race. In the model that further adjusted for other coping styles, terminal illness acknowledgment, support of spiritual needs, preference for heroics, and advance care planning (do-not-resuscitate order, living will, and health care proxy/durable power of attorney), positive religious coping remained a significant predictor of receiving intensive life-prolonging care near death (AOR, 2.90 [95% CI, 1.07-7.89]; P = .04).<h3>Conclusions</h3>Positive religious coping in patients with advanced cancer is associated with receipt of intensive life-prolonging medical care near death. Further research is needed to determine the mechanisms for this association.