tbuckley/cabot-search huggingface dataset:
The JAK2 V617F mutation is rare in RARS but common in RARS-T
Authors: M M Ceesay, N C Lea, W Ingram, N B Westwood, J Gäken, A Mohamedali, J Cervera, U Germing, N Gattermann, A Giagounidis, Z Garcia-Casado, G Sanz, G J Mufti
Journal: Leukemia (2006)
Evaluation of the echocardiogram as an epidemiologic tool in an asymptomatic population.
Authors: R S Valdez, J A Motta, E London, R P Martin, W L Haskell, J W Farquhar, R L Popp, L Horlick
Journal: Circulation (1979)

An asymptomatic adult population of 196 men and women was studied with the echocardiogram to derive age- and sex-specific "normal" values for a number of clinically used echocardiograhic variables. The results are in general agreement with previously published normal values. Body position during the examination, age and sex influence the echocardiographic results; body surface area correction normalized most of these effects. The prevalence of occult abnormalities determined by the echocardiogram is 7%; the most common finding was mitral valve prolapse. Inter- and intraobserver variability was assessed. The interobserver differences found on analysis are statistically, but not clinically , significant. The echocardiogram appears to be a suitable tool to use in epidemiologic studies to detect selected cardiac abnormalities, but is limited for this purpose because some subjects in such a population cannot be adequately examined.
Effects of nifedipine on myocardial perfusion and ischemic injury in dogs.
Authors: P D Henry, R Shuchleib, L J Borda, R Roberts, J R Williamson, B E Sobel
Journal: Circulation Research (1978)

To determine whether nifedipine, a calcium antagonist, protects ischemic myocardium, conscious dogs were subjected to coronary occlusion and given nifedipine by intravenous infusion beginning 30 minutes after the onset of ischemia and lasting for 24 hours while systemic arterial pressure, left atrial pressure, and cardiac output were monitored. Local myocardial perfusion at selected intervals after coronary occlusion was assessed with radioactive microspheres injected into the left atrium. In regions of myocardium exhibiting moderately depressed flow 29 minutes after occlusion in control dogs (n = 8), flow was significantly greater 3 and 23.5 hours later, reflecting increases in collateral perfusion. Corresponding zones of myocardium in treated dogs (n = 9) exhibited significantly greater increases in flow at each interval after occlusion (P less than 0.05). Furthermore, myocardial creatine kinase depletion (which correlated well with morphometric estimates of necrosis) in myocardium matched for ischemia prior to treatment was 1.5 to 3 times less in treated than in control dogs (P less than 0.05). Thus, nifedipine produced sustained increases in collateral flow and reduced myocardial ischemic injury.
The devil is in the detail of the government's response to the Francis report
Authors: P. de Zulueta
Journal: BMJ (2013)

The government’s preliminary response to the Francis report merits careful reading. Embedded in text strewn with words such as “compassion” and “courage” are some worrying caveats.1 For example, whistleblowing is encouraged and gagging clauses are condemned, but then it says that any confidentiality clauses should go no further than is necessary “to protect patient confidentiality or …
Regulation of Proangiogenic Factor CCN1 in Cardiac Muscle
Authors: Denise Hilfiker-Kleiner, Karol Kaminski, Agnieszka Kaminska, Martin Fuchs, Gunnar Klein, Edith Podewski, Karsten Grote, Ioulia Kiian, Kai C. Wollert, Andres Hilfiker, Helmut Drexler
Journal: Circulation (2004)

Background— CCN1, a potent proangiogenic factor, is induced in the vasculature by tissue injury, angiotensin II (Ang II), and growth factor stimulation. Because these conditions occur in myocardial ischemia and pressure overload, we investigated the regulation of CCN1 in cardiomyocytes in vitro and in the heart in vivo. Methods and Results— Ang II, signaling via the angiotensin type 1 (AT 1 ) receptor, and α 1 -adrenergic stimulation with phenylephrine induced CCN1 expression in ventricular cardiomyocytes isolated from 1- to 3-day-old rats. Cell culture supernatant of Ang II–treated cardiomyocytes induced migration of smooth muscle cells, which was abolished by neutralizing antibody to CCN1. Ang II– and phenylephrine-mediated induction of CCN1 expression in cardiomyocytes was completely abolished by inhibition of MEK/extracellular signal–regulated kinases (ERK) or protein kinase C (PKC). Likewise, mechanical stretch induced CCN1 expression in cardiomyocytes, an effect that was prevented by AT 1 receptor blockade or PKC inhibition. Similarly, pressure overload in vivo upregulated myocardial CCN1 expression levels via AT 1 receptor– and PKC-dependent mechanisms. After myocardial infarction in mice, CCN1 expression was strongly induced in both ischemic and remote left ventricular myocardium. Marked CCN1 protein expression was noted in cardiomyocytes of patients with end-stage ischemic cardiomyopathy but was almost absent in nonfailing human myocardium. Conclusions— Pressure overload, ischemia, and neurohormonal factors, such as Ang II or α 1 -adrenergic stimuli, induce myocardial expression of CCN1, a potent proangiogenic factor, supporting the notion that CCN1 may play an important role in the adaptation of the heart to cardiovascular stress.
Aftercare of the Psychiatric Patient: An 1847 View
Authors: ERNEST HARMS
Journal: American Journal of Psychiatry (1968)

Dr. F. Koestl, in 1847, wrote of the necessity of dignified attitudes toward, and proper aftercare facilities for, recovered and recovering mental patients. His 196-page book, written 121 years ago, anticipated some of modern psychiatry's ideas regarding aftercare and social readjustment.
Receptor-Independent Cardiac Protein Kinase Cα Activation by Calpain-Mediated Truncation of Regulatory Domains
Authors: Min-Young Kang, Yan Zhang, Scot J. Matkovich, Abhinav Diwan, Athar H. Chishti, Gerald W. Dorn
Journal: Circulation Research (2010)

Rationale: Protein kinase (PK)Cs and calpain cysteine proteases are highly expressed in myocardium. Ischemia produces calcium overload that activates calpains and conventional PKCs. However, calpains can proteolytically process PKCs, and the potential in vivo consequences of this interaction are unknown. Objective: To determine the biochemical and pathophysiological consequences of calpain-mediated cardiac PKCα proteolysis. Methods and Results: Isolated mouse hearts subjected to global ischemia/reperfusion demonstrated cleavage of PKCα. Calpain 1 overexpression was not sufficient to produce PKCα cleavage in normal hearts, but ischemia-induced myocardial PKCα cleavage and myocardial injury were greatly increased by cardiac-specific expression of calpain 1. In contrast, calpain 1 gene ablation or inhibition with calpastatin prevented ischemia/reperfusion induced PKCα cleavage; infarct size was decreased and ventricular function enhanced in infarcted calpain 1 knockout hearts. To determine consequences of PKCα fragmentation on myocardial protein phosphorylation, transgenic mice were created conditionally expressing full-length PKCα or its N-terminal and C-terminal calpain 1 cleavage fragments. Two-dimensional mapping of ventricular protein extracts showed a distinct PKCα phosphorylation profile that was exaggerated and distorted in hearts expressing the PKCα C-terminal fragment. MALDI mass spectroscopy revealed hyperphosphorylation of myosin-binding protein C and phosphorylation of atypical substrates by the PKCα C-terminal fragment. Expression of parent PKCα produced a mild cardiomyopathy, whereas myocardial expression of the C-terminal PKCα fragment induced a disproportionately severe, rapidly lethal cardiomyopathy. Conclusions: Proteolytic processing of PKCα by calcium-activated calpain activates pathological cardiac signaling through generation of an unregulated and/or mistargeted kinase. Production of the PKCα C-terminal fragment in ischemic hearts occurs via a receptor-independent mechanism.
Progressive Chromatin Repression and Promoter Methylation of <i>CTNNA1</i> Associated with Advanced Myeloid Malignancies
Authors: Ying Ye, Michael A. McDevitt, Mingzhou Guo, Wei Zhang, Oliver Galm, Steven D. Gore, Judith E. Karp, Jaroslaw P. Maciejewski, Jeanne Kowalski, Hua-Ling Tsai, Lukasz P. Gondek, Hsing-Chen Tsai, Xiaofei Wang, Craig Hooker, B. Douglas Smith, Hetty E. Carraway, James G. Herman
Journal: Cancer Research (2009)

Complete loss or deletion of the long arm of chromosome 5 is frequent in myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). The putative gene(s) deleted and responsible for the pathogenesis of these poor prognosis hematologic disorders remain controversial. This study is a comprehensive analysis of previously implicated and novel genes for epigenetic inactivation in AML and MDS. In 146 AML cases, methylation of CTNNA1 was frequent, and more common in AML patients with 5q deletion (31%) than those without 5q deletion (14%), whereas no methylation of other 5q genes was observed. In 31 MDS cases, CTNNA1 methylation was only found in high-risk MDS (>or=RAEB2), but not in low-risk MDS (<RAEB2), indicating that CTNNA1 methylation might be important in the transformation of MDS to AML. CTNNA1 expression was lowest in AML/MDS patients with CTNNA1 methylation, although reduced expression was found in some patients without promoter methylation. Repressive chromatin marks (H3K27me3) at the promoter were identified in CTNNA1-repressed AML cell lines and primary leukemias, with the most repressive state correlating with DNA methylation. These results suggest progressive, acquired epigenetic inactivation at CTNNA1, including histone modifications and promoter CpG methylation, as a component of leukemia progression in patients with both 5q- and non-5q- myeloid malignancies.
Statin Therapy, LDL Cholesterol, C-Reactive Protein, and Coronary Artery Disease
Authors: Steven E. Nissen, E. Murat Tuzcu, Paul Schoenhagen, Tim Crowe, William J. Sasiela, John Tsai, John Orazem, Raymond D. Magorien, Charles O'Shaughnessy, Peter Ganz
Journal: New England Journal of Medicine (2005)

Recent trials have demonstrated better outcomes with intensive than with moderate statin treatment. Intensive treatment produced greater reductions in both low-density lipoprotein (LDL) cholesterol and C-reactive protein (CRP), suggesting a relationship between these two biomarkers and disease progression.We performed intravascular ultrasonography in 502 patients with angiographically documented coronary disease. Patients were randomly assigned to receive moderate treatment (40 mg of pravastatin orally per day) or intensive treatment (80 mg of atorvastatin orally per day). Ultrasonography was repeated after 18 months to measure the progression of atherosclerosis. Lipoprotein and CRP levels were measured at baseline and follow-up.In the group as a whole, the mean LDL cholesterol level was reduced from 150.2 mg per deciliter (3.88 mmol per liter) at baseline to 94.5 mg per deciliter (2.44 mmol per liter) at 18 months (P<0.001), and the geometric mean CRP level decreased from 2.9 to 2.3 mg per liter (P<0.001). The correlation between the reduction in LDL cholesterol levels and that in CRP levels was weak but significant in the group as a whole (r=0.13, P=0.005), but not in either treatment group alone. In univariate analyses, the percent change in the levels of LDL cholesterol, CRP, apolipoprotein B-100, and non-high-density lipoprotein cholesterol were related to the rate of progression of atherosclerosis. After adjustment for the reduction in these lipid levels, the decrease in CRP levels was independently and significantly correlated with the rate of progression. Patients with reductions in both LDL cholesterol and CRP that were greater than the median had significantly slower rates of progression than patients with reductions in both biomarkers that were less than the median (P=0.001).For patients with coronary artery disease, the reduced rate of progression of atherosclerosis associated with intensive statin treatment, as compared with moderate statin treatment, is significantly related to greater reductions in the levels of both atherogenic lipoproteins and CRP.
Clinical manifestations, co-sensitizations, and immunoblotting profiles of buckwheat-allergic patients
Authors: E. Heffler, F. Nebiolo, R. Asero, G. Guida, I. Badiu, S. Pizzimenti, C. Marchese, S. Amato, G. Mistrello, F. Canaletti, G. Rolla
Journal: Allergy (2010)

Buckwheat allergy is a rare food allergy in Europe and North America, whereas it is often described and studied in Asia. The aim of this study was to describe a series of patients with proven buckwheat allergy evaluated in an Italian allergy clinic. Co-sensitization to other food and inhalant allergens and immunoblotting profiles of buckwheat-allergic patients were studied. Patients with suspected buckwheat allergy who attended the allergy clinic between January 1, 2006, and September 30, 2008, were evaluated. All patients underwent skin prick tests for a standard panel of inhalant and food allergens, prick-by-prick with buckwheat flour, buckwheat-specific IgE determinations, and double-blind placebo-controlled food challenge (DBPCFC) with buckwheat flour. Immunoblotting with buckwheat flour extract was performed on sera from buckwheat-allergic patients. Among 72 patients with suspected buckwheat allergy, 30 (41.7%) were sensitized to buckwheat and 24 had a positive DBPCFC. The mean buckwheat IgE level was 6.23 kUA/l (range, 0.16 to >100 kUA/l). Several IgE-binding proteins were identified and grouped into three patterns: a 16-kDa band in patients with predominantly gastrointestinal symptoms with grass and wheat flour co-sensitization, a 25-kDa band in patients with predominantly cutaneous symptoms and a low frequency of co-sensitization, and a 40-kDa band in patients with anaphylaxis and a low frequency of co-sensitization. Buckwheat allergy is an emerging food allergy in Italy. We identified three distinct patterns of clinical and laboratory characteristics, suggesting that specific allergens could be more frequently associated with clinical manifestations of different severity.
Prognostic Value of Histologic Subtypes in Renal Cell Carcinoma: A Multicenter Experience
Authors: Jean-Jacques Patard, Emmanuelle Leray, Nathalie Rioux-Leclercq, Luca Cindolo, Vincenzo Ficarra, Amnon Zisman, Alexandre De La Taille, Jacques Tostain, Walter Artibani, Claude C. Abbou, Bernard Lobel, François Guillé, Dominique K. Chopin, Peter F.A. Mulders, Christopher G. Wood, David A. Swanson, Robert A. Figlin, Arie S. Belldegrun, Allan J. Pantuck
Journal: Journal of Clinical Oncology (2005)

To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience.Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively.Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001).The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.
Ectopic Hypercellular Parathyroid Tissue of the Mediastinum Masquerading As Metastatic Adenocarcinoma on Positron Emission Tomography–Computed Tomography Scan
Authors: Charu Aggarwal, William Y. Shi, Christopher D. Watt, Vivianna M. van Deerlin, Andrew R. Haas, Charles B. Simone, Gordon H. Yu
Journal: Journal of Clinical Oncology (2014)
Transverse myelopathy and radiculomyelopathy associated with pulmonary atypical Mycobacterium infections
Authors: V L C White, R Al-Shahi, E Gamble, P Brown, A G Davison
Journal: Thorax (2001)

Myelopathy is a well recognised but rare association with<i>Mycobacterium tuberculosis </i>infection, but has not been described with atypical mycobacteria. We report two cases of disabling myelopathy in association with pulmonary infection by<i>Mycobacterium kansasii</i> and<i>Mycobacterium malmoense</i>; the myelopathy is presumed to be a para-infectious phenomenon.
Clinical and biologic activity of the farnesyltransferase inhibitor R115777 in adults with refractory and relapsed acute leukemias: a phase 1 clinical-laboratory correlative trial
Authors: Judith E. Karp, Jeffrey E. Lancet, Scott H. Kaufmann, David W. End, John J. Wright, Kees Bol, Ivan Horak, Michael L. Tidwell, Jane Liesveld, Timothy J. Kottke, Dawn Ange, Laxmi Buddharaju, Ivana Gojo, W. Edward Highsmith, Robert T. Belly, Raymond J. Hohl, Mary Ellen Rybak, Alain Thibault, Joseph Rosenblatt
Journal: Blood (2001)
Giant cell versus lymphocytic myocarditis. A comparison of their clinical features and long-term outcomes.
Authors: R Davidoff, I Palacios, J Southern, J T Fallon, J Newell, G W Dec
Journal: Circulation (1991)

Giant cell myocarditis has rarely been diagnosed premortem, and little is known about its natural history. In addition, no comparative studies with lymphocytic myocarditis exist.The clinical features, serial change in left ventricular fraction (LVEF), and outcomes of all patients with histologically verified myocarditis were retrospectively evaluated. Ten patients (22%) were found to have giant cell myocarditis (group 1), whereas the remaining 36 (78%) had lymphocytic myocarditis (group 2). Age at presentation, gender distribution, duration of symptoms, initial LVEF, and resting hemodynamics did not differ between groups. Ventricular tachycardia was detected in 90% of group 1 patients compared with only 25% of group 2 (p = 0.0007). Atrioventricular block that required pacemaker insertion was also more common in group 1 (60%) than in group 2 (8.3%) (p = 0.001). Left ventricular systolic function declined during follow-up in group 1 patients (LVEF, 0.43 +/- 0.07-0.26 +/- 0.05, p = 0.11) but increased in group 2 patients (LVEF, 0.33 +/- 0.03-0.41 +/- 0.03, p = 0.02). When the net change between initial and final LVEF was assessed, a significant difference was evident (giant cell group, -0.17 +/- 0.06; lymphocytic group, +0.07 +/- 0.03; p = 0.0008). Although a greater proportion of patients in group 1 died or required transplantation (seven of 10 versus 11 of 36, p = 0.03), actuarial survival over 4 years was not different for the giant cell group (50%) than for the lymphocytic group (62%).Giant cell myocarditis was more prevalent than previously recognized and highly associated with both ventricular tachycardia and pacemaker requirement. The likelihood of an adverse event, either cardiovascular mortality or cardiac transplantation, was significantly greater for patients with giant cell myocarditis than for those with lymphocytic myocarditis, perhaps because of the progressive decline in left ventricular systolic function that was observed in those with giant cell myocarditis.
Histological and Clinical Evolution of Lupus Nephritis
Authors: R. C. Muehrcke, R. M. Kark, C. L. Pirani, V. E. Pollak, I. E. Steck
Journal: Annals of the Rheumatic Diseases (1955)

In recent years, lupus nephritis has become the major complication and the most pressing problem in patients suffering from lupus erythematosus disseminatus.The clinical course of the disease was different 15 years ago, when Keith (1940) wrote that "renal insufficiency does not play an important role in causing death".At that time patients usually died of a "lupus crisis" or as a result of concurrent infection.However, the use of anti- biotics, blood transfusions, balanced water and electrolyte therapy, steroid hormone therapy, and injections of corticotropin has, apparently, pro- longed life in those afflicted with systemic lupus erythematosus (S.L.E.).With present methods of care many such patients can usually be kept free of symptoms for a considerable length of time, only to succumb to a rapidly progressive renal failure.Because of the problems raised by the increased incidence of lupus nephritis, a study of the histo- logical evolution of renal involvement in S.L.E. was begun, using serial percutaneous renal biopsies (Kark and Muehrcke, 1954; Muehrcke and others, 1955a).Histological data were correlated with changing clinical status, clinical laboratory data, and renal function tests in a continuing study of the pathophysiology and natural history of lupus nephritis.Preliminary observations have been reported else- where (Pirani and others, 1954; Muehrcke and others, 1955b).This communication outlines some observations on 34 patients studied intensively during the past 18 months.
Endoscopic closure of bronchial fistula.
Authors: H Roksvaag, L Skalleberg, C Nordberg, K Solheim, B Hoivik
Journal: Thorax (1983)

The treatment of bronchopleural fistula still carries a high morbidity and mortality, especially after pneumonectomy.We report two cases treated by endoscopic application of tissue glue. Case reportsCase I A 62 year old man was admitted to the Central County
Bronchial compression as a result of lung herniation after pneumonectomy.
Authors: K F Whyte, G McMahon, A J Wightman, E W Cameron
Journal: Thorax (1991)

A patient developed severe exertional dyspnoea and stridor eight months after a right pneumonectomy for a carcinoid tumour, with a progressive loss of lung function. These events were the result of compression of the left main bronchus against the vertebral column by the mediastinal contents, which had shifted into the right hemithorax with the herniated lung.
Long-Term Effect of Goal-Directed Weight Management in an Atrial Fibrillation Cohort
Authors: Rajeev K. Pathak, Melissa E. Middeldorp, Megan Meredith, Abhinav B. Mehta, Rajiv Mahajan, Christopher X. Wong, Darragh Twomey, Adrian D. Elliott, Jonathan M. Kalman, Walter P. Abhayaratna, Dennis H. Lau, Prashanthan Sanders
Journal: Journal of the American College of Cardiology (2015)
Spontaneous redistribution of surface immunoglobulin in the motile B lymphocyte.
Authors: G F Schreiner, J Braun, E R Unanue
Journal: The Journal of Experimental Medicine (1976)

This paper reports that B cells undergoing translatory motion spontaneously segregate their surface Ig to one portion of their plasma membrane. The spontaneous redistribution of surface Ig was found to be: (a) selective, concanavalin A-dependent on translatory motion and energy metabolism. Abundant B cells undergoing motility were found after cultures in lipopolysaccharide or trypsin, or after brief exposure to cholinergic drugs.