tbuckley/cabot-search huggingface dataset:
Malignant pleural mesothelioma
Authors: C Boutin, M Schlesser, C Frenay, P Astoul
Journal: European Respiratory Journal (1998)

The incidence of malignant pleural mesothelioma (MPM) has risen for some decades and is expected to peak between 2010 and 2020. Up to now, no single treatment has been proven to be effective and death usually occurs within about 12-17 months after diagnosis. Perhaps because of this poor prognosis, early screening has incited little interest. However, certain forms may have a better prognosis when diagnosed early and treated by multimodal therapy or intrapleural immunotherapy. Diagnosis depends foremost on histological analysis of samples obtained by thoracoscopy. This procedure allows the best staging of the pleural cavity with an attempt to detect visceral pleural involvement, which is one of the most important prognostic factors. Although radiotherapy seems necessary and is efficient in preventing the malignant seeding after diagnostic procedures in patients, there has been no randomized phase III study showing the superiority of any treatment compared with another. However, for the early-stage disease (stage I) a logical therapeutic approach seems to be neoadjuvant intrapleural treatment using cytokines. For more advanced disease (stages II and III) resectability should be discussed with the thoracic surgeons and a multimodal treatment combining surgery, radiotherapy and chemotherapy should be proposed for a randomized controlled study. Palliative treatment is indicated for stage IV. In any case, each patient should be enrolled in a clinical trial.
False Aneurysm of the Left Ventricle Secondary to Bacterial Endocarditis with Perforation of the Mitral-Aortic Intervalvular Fibrosa
Authors: ELLIOT CHESLER, MICHAEL E. KORNS, GERALD E. PORTER, CESAR N. REYES, JESSE E. EDWARDS
Journal: Circulation (1968)

In an infant with bacterial endocarditis of the aortic valve a mycotic false aneurysm of the left ventricular outflow tract was a complication. The unusual nature of the case relates to the fact that the mouth of the false aneurysm lay in the mitral-aortic intervalvular fibrosa, the junctional tissue between the mitral and aortic valves. The close relationship between this structure and the epicardium was responsible for the peculiar location of the aneurysm in the epicardium between the aorta and the left atrium. Rupture of the false aneurysm led to a fatal hemopericardium.
Prokineticins and the heart: diverging actions elicited by signalling through prokineticin receptor-1 or -2
Authors: H. Attramadal
Journal: Cardiovascular Research (2008)

Prokineticins are a family of secreted, small, chemokine-like peptides first identified during the previous decade (for review see ref. 1 and 2). Two distinct members are currently known, prokineticin-1 and prokineticin-2, which mediate their biological activities by signalling through two homologous G protein-coupled receptors (7-transmembrane segment receptors), prokineticin receptor-1 (PKR-1), and prokineticin receptor-2 (PKR-2).1 Phylogenetically, the prokineticins display the highest similarity with defencins. Although our knowledge about the biological actions and pathophysiological implications of prokineticin-1 and -2 is in its infancy, current reports indicate a wide array of biological functions in many different tissues including the cardiovascular system.1,2 Elucidation of the emerging roles of prokineticins in cardiovascular physiology and pathophysiology is based on recent reports by Nebigil and colleagues,3,4 one of which is published in this issue of Cardiovascular Research .

Prokineticins were first named for their ability to stimulate longitudinal smooth muscle contraction in guinea pig ileum.1,2 However, in the mouse prokineticins and prokineticin receptors are most abundant in … 

*Corresponding author. Tel: +47 23073520; fax: 47 23073530. E-mail address : havard.attramadal{at}medisin.uio.no
LYN-activating mutations mediate antiestrogen resistance in estrogen receptor–positive breast cancer
Authors: Luis J. Schwarz, Emily M. Fox, Justin M. Balko, Joan T. Garrett, María Gabriela Kuba, Mónica Valeria Estrada, Ana María González-Angulo, Gordon B. Mills, Monica Red-Brewer, Ingrid A. Mayer, Vandana Abramson, Monica Rizzo, Mark C. Kelley, Ingrid M. Meszoely, Carlos L. Arteaga
Journal: Journal of Clinical Investigation (2014)

Estrogen receptor-positive (ER(+)) breast cancers adapt to hormone deprivation and become resistant to antiestrogen therapy. Here, we performed deep sequencing on ER(+) tumors that remained highly proliferative after treatment with the aromatase inhibitor letrozole and identified a D189Y mutation in the inhibitory SH2 domain of the SRC family kinase (SFK) LYN. Evaluation of 463 breast tumors in The Cancer Genome Atlas revealed four LYN mutations, two of which affected the SH2 domain. In addition, LYN was upregulated in multiple ER(+) breast cancer lines resistant to long-term estrogen deprivation (LTED). An RNAi-based kinome screen revealed that LYN is required for growth of ER(+) LTED breast cancer cells. Kinase assays and immunoblot analyses of SRC substrates in transfected cells indicated that LYN(D189Y) has higher catalytic activity than WT protein. Further, LYN(D189Y) exhibited reduced phosphorylation at the inhibitory Y507 site compared with LYN(WT). Other SH2 domain LYN mutants, E159K and K209N, also exhibited higher catalytic activity and reduced inhibitory site phosphorylation. LYN(D189Y) overexpression abrogated growth inhibition by fulvestrant and/or the PI3K inhibitor BKM120 in 3 ER(+) breast cancer cell lines. The SFK inhibitor dasatinib enhanced the antitumor effect of BKM120 and fulvestrant against estrogen-deprived ER(+) xenografts but not LYN(D189Y)-expressing xenografts. These results suggest that LYN mutations mediate escape from antiestrogens in a subset of ER(+) breast cancers.
Total therapy 2 without thalidomide in comparison with total therapy 1: role of intensified induction and posttransplantation consolidation therapies
Authors: Bart Barlogie, Guido Tricot, Erik Rasmussen, Elias Anaissie, Frits van Rhee, Maurizio Zangari, Athanasios Fassas, Klaus Hollmig, Mauricio Pineda-Roman, John Shaughnessy, Joshua Epstein, John Crowley
Journal: Blood (2005)
Heterochromatin condensation and evolution of unique satellite-DNA families in two parasitic wasp species: Diadromus pulchellus and Eupelmus vuilleti (Hymenoptera).
Authors: Y Bigot, M H Hamelin, G Periquet
Journal: Molecular Biology and Evolution (1990)

Large quantities of satellite DNA families (15%-25% of the genome) were found in the DNA of two species of parasitic wasps, Diadromus pulchellus and Eupelmus vuilleti. In both species the satellite DNA was found to consist wholly or largely of a single family unique to that species. Several clones of each family were obtained and sequenced. Palindromes in each consensus sequence suggest the formation in vivo of hairpin structures that may play a role in the mode of heterochromatin condensation in these insects. The ancestral repeating motifs were determined from the consensus sequences. Plausible scenarios are presented for the evolution of the two satellite DNAs. The occurrence of only one family of satellite DNAs in both species may indicate that, in male haploids, such families have shorter persistence times than necessary for the origins of new duplicated sequences.
Comparison of Two Murine Models of Familial Hypertrophic Cardiomyopathy
Authors: Bradley K. McConnell, Diane Fatkin, Christopher Semsarian, Karen A. Jones, Dimitrios Georgakopoulos, Colin T. Maguire, Michael J. Healey, James O. Mudd, Ivan P. G. Moskowitz, David A. Conner, Michael Giewat, Hiroko Wakimoto, Charles I. Berul, Frederick J. Schoen, David A. Kass, Christine E. Seidman, J. G. Seidman
Journal: Circulation Research (2001)

Abstract —Although sarcomere protein gene mutations cause familial hypertrophic cardiomyopathy (FHC), individuals bearing a mutant cardiac myosin binding protein C ( MyBP-C ) gene usually have a better prognosis than individuals bearing β -cardiac myosin heavy chain (MHC) gene mutations. Heterozygous mice bearing a cardiac MHC missense mutation (αMHC 403/+ or a cardiac MyBP-C mutation (MyBP-C t/+ ) were constructed as murine FHC models using homologous recombination in embryonic stem cells. We have compared cardiac structure and function of these mouse strains by several methods to further define mechanisms that determine the severity of FHC. Both strains demonstrated progressive left ventricular (LV) hypertrophy; however, by age 30 weeks, αMHC 403/+ mice demonstrated considerably more LV hypertrophy than MyBP-C t/+ mice. In older heterozygous mice, hypertrophy continued to be more severe in the αMHC 403/+ mice than in the MyBP-C t/+ mice. Consistent with this finding, hearts from 50-week-old αMHC 403/+ mice demonstrated increased expression of molecular markers of cardiac hypertrophy, but MyBP-C t/+ hearts did not demonstrate expression of these molecular markers until the mice were &gt;125 weeks old. Electrophysiological evaluation indicated that MyBP-C t/+ mice are not as likely to have inducible ventricular tachycardia as αMHC 403/+ mice. In addition, cardiac function of αMHC 403/+ mice is significantly impaired before the development of LV hypertrophy, whereas cardiac function of MyBP-C t/+ mice is not impaired even after the development of cardiac hypertrophy. Because these murine FHC models mimic their human counterparts, we propose that similar murine models will be useful for predicting the clinical consequences of other FHC-causing mutations. These data suggest that both electrophysiological and cardiac function studies may enable more definitive risk stratification in FHC patients.
Crucial role for the VWF A1 domain in binding to type IV collagen
Authors: Veronica H. Flood, Abraham C. Schlauderaff, Sandra L. Haberichter, Tricia L. Slobodianuk, Paula M. Jacobi, Daniel B. Bellissimo, Pamela A. Christopherson, Kenneth D. Friedman, Joan Cox Gill, Raymond G. Hoffmann, Robert R. Montgomery
Journal: Blood (2015)
Rational design of shepherdin, a novel anticancer agent
Authors: Janet Plescia, Whitney Salz, Fang Xia, Marzia Pennati, Nadia Zaffaroni, Maria Grazia Daidone, Massimiliano Meli, Takehiko Dohi, Paola Fortugno, Yulia Nefedova, Dmitry I. Gabrilovich, Giorgio Colombo, Dario C. Altieri
Journal: Cancer Cell (2005)
Chronic obstructive pulmonary disease * 10: Bullectomy, lung volume reduction surgery, and transplantation for patients with chronic obstructive pulmonary disease
Authors: B F Meyers
Journal: Thorax (2003)

There are currently three surgical treatments for emphysema: bullectomy, lung transplantation, and lung volume reduction surgery (LVRS). Unfortunately, most emphysema patients are poor candidates for any surgical intervention. A meticulous selection process is favoured in which indications and contraindications are considered and the best solution is devised for each patient. Patients with giant bullae filling half the thoracic volume and compressing relatively normal adjacent parenchyma are offered bullectomy; those with hyperinflation, heterogeneous distribution of destruction, forced expiratory volume in 1 second (FEV<sub>1</sub>) &gt;20%, and a normal carbon dioxide tension (Pco<sub>2</sub>) are offered LVRS; and patients with diffuse disease, lower FEV<sub>1</sub>, hypercapnia, and associated pulmonary hypertension are directed towards transplantation. Using these criteria, few patients are serious candidates for surgical procedures. Combinations of LVRS and lung transplantation, either simultaneously or sequentially, are possible but rarely necessary.
Phase I Clinical Trial of Intrathecal Topotecan in Patients With Neoplastic Meningitis
Authors: Susan M. Blaney, Richard Heideman, Stacey Berg, Peter Adamson, Andy Gillespie, J. Russell Geyer, Roger Packer, Kate Matthay, Kurt Jaeckle, Diane Cole, Nancy Kuttesch, David G. Poplack, Frank M. Balis
Journal: Journal of Clinical Oncology (2002)

Purpose: A phase I trial of intrathecal (IT) topotecan was performed to determine the optimal dose, the dose-limiting toxic effects, and the incidence and severity of other toxic effects in patients 3 years and older with neoplastic meningitis. Patients and Methods: Twenty-three assessable patients received IT topotecan administered by means of either lumbar puncture or an indwelling ventricular access device (Ommaya reservoir). Intrapatient dose escalation from 0.025 mg to 0.2 mg was performed in the first cohort of patients. Subsequent cohorts of patients were treated at fixed dose levels of 0.2 mg, 0.4 mg, or 0.7 mg. Serial samples of CSF for pharmacokinetic studies were obtained in a subset of patients with Ommaya reservoirs. Results: Arachnoiditis, characterized by fever, nausea, vomiting, headache, and back pain, was the dose-limiting toxic effect in two of four patients enrolled at the 0.7 mg dose level. The maximum-tolerated dose (MTD) was 0.4 mg. Six of the 23 assessable patients had evidence of benefit manifested as prolonged disease stabilization or response. Conclusion: The MTD and recommended phase II dose of IT topotecan in patients who are 3 years or older is 0.4 mg. A phase II trial of IT topotecan in children with neoplastic meningitis is in progress.
The effect of anticholinergic drugs on the mucus content of gastric juice
Authors: D. W. Piper, M. C. Stiel, B. Fenton
Journal: Gut (1962)

Increasing suppression of gastric secretion by anticholinergic drugs is accompanied by a rising mucus concentration; the actual output of mucus shows little change despite a marked reduction in the secretory volume. The problems involved in the estimation of mucus secretion and the importance of the above findings in relation to the therapeutic use of anticholinergic drugs in peptic ulceration are discussed.
T cell stimulation via the erythrocyte receptor. Synergism between monoclonal antibodies and phorbol myristate acetate without changes of free cytoplasmic Ca++ levels.
Authors: W Holter, G F Fischer, O Majdic, H Stockinger, W Knapp
Journal: The Journal of Experimental Medicine (1986)

We observed that certain E-receptor antibodies (CD2 antibodies) can induce proliferation of resting human T cells in the presence of PMA, while other CD2 antibodies fail to have such an effect. The same CD2 antibodies that were mitogenic in the presence of PMA (9.6, X11, VIT13), but not the nonreactive ones, were also able to induce T cell proliferation via the so-called alternative pathway of T cell activation, i.e., when added pairwise in certain combinations to T cells in the absence of PMA. While the simultaneous addition of two comitogenic CD2 antibodies (9.6 or X11 plus VIT13) or the addition of a single nonmitogenic CD3 antibody (VIT3) led to a clearcut elevation of intracellular Ca++ levels, no such effect could be observed after the addition of one CD2 antibody alone. Even in the presence of PMA, one comitogenic CD2 antibody alone was unable to trigger a significant Ca++ response, although this combination induced a proliferative response. These data indicate that, distinguishable by their influence on free cytoplasmic Ca++, there are two different mechanisms of T cell activation via CD2. While simultaneous triggering with two antibodies leads to cell proliferation preceded by an increase of Ca++ levels, stimulation with one antibody plus PMA results in proliferation without a measurable early Ca++ response. We conclude that T cells treated by certain CD2 antibodies alone already recognize an activation signal probably unrelated to Ca++ homeostasis, a signal that can further be developed by PMA to result in a completely developed proliferative response.
Key players for new GP-led commissioning are already leaving jobs
Authors: A. O'Dowd
Journal: BMJ (2010)

Expert managers in primary care trusts who could provide invaluable help to the new GP-led commissioning consortiums are already accepting redundancy, MPs have been told.

Doctors’ leaders giving evidence to the parliamentary health select committee on 2 November warned that the government should ensure there was a managed transition to the new NHS arrangements in which GP consortiums will control most of the NHS budget.

The worry was that expert managers were already leaving and might have to be re-employed by GP consortiums at a much higher cost from private sector companies.

MPs on the committee quizzed doctor representatives as part of their inquiry into how the government intends …
Amiodarone-induced hepatic phospholipidosis: Correlation of morphological and biochemical findings in an animal model
Authors: Mauro Pirovino, Otfried Müller, Thomas Zysset, Ueli Honegger
Journal: Hepatology (1988)

Morphological and biochemical investigations were performed in guinea pigs after 1, 3, 5 and 16 weeks of amiodarone feeding. The most prominent morphological finding was an increase in dense bodies in hepatocytes, Kupffer cells and in bile duct epithelia, reaching a maximum after 5 weeks of treatment according to morphometric analysis. Similar time courses were observed for the serum and liver tissue concentrations of amiodarone and desethylamiodarone and the—albeit minimal—extent of hepatocellular necrosis. Phospholipids in the liver homogenate were unchanged after 1 week, but significantly increased after prolonged amiodarone treatment. There was no significant alteration in the pattern of individual phospholipids. Serum and tissue concentrations as well as the extent of phospholipidosis do not appear to be a function of the duration of drug application. A very close correlation, however, was observed between the liver tissue concentration of amiodarone and the amount of dense bodies as a morphological expression of phospholipidosis.
A distinct subset of submucosal mast cells undergoes hyperplasia following neonatal maternal separation: a role in visceral hypersensitivity?
Authors: N P Hyland, M Julio-Pieper, S M O'Mahony, D C Bulmer, K Lee, E M Quigley, T G Dinan, J F Cryan
Journal: Gut (2009)

<h3>OBJECTIVE</h3> It has been hypothesised, mainly on the basis of indirect evidence, that low serum concentrations of androgen-anabolic hormones would play a causal part in the aetiology of rheumatoid arthritis (RA). <h3>METHODS</h3> A case-control study was nested with a Finnish cohort of 19 072 adults who had neither arthritis nor a history of it at the baseline examination during 1973–1977. Pre-illness serum specimens for the assay of testosterone and dehydroepiandrosterone sulphate (DHEAS) were available from 116 cases who had developed RA by late 1989. Three controls per each incident case were individually matched for sex, age, and municipality. <h3>RESULTS</h3> The mean testosterone concentration was 1.4 nmol/l in those 84 women who developed RA and 1.4 nmol/l in their controls; the corresponding figures for DHEAS were 5.2 μmol/l and 5.5 μmol/l, respectively. Mean testosterone concentration in the 32 male cases was 26.1 nmol/l and 26.4 nmol/l in their controls; the corresponding figures for DHEAS were 11.2 μmol/l and 10.1 μmol/l, respectively. Analysis by subgroups (rheumatoid factor positive and negative disease, premenopausal and postmenopausal women) and by hormone distributions showed no differences. <h3>CONCLUSION</h3> The findings are not in line with the contention that low concentrations of testosterone and DHEAS play a part in the aetiology of RA.
Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study
Authors: John N Nanas, George Alexopoulos, Maria I Anastasiou-Nana, Konstantinos Karidis, Argiris Tirologos, Spyridon Zobolos, Vlasios Pirgakis, Labros Anthopoulos, Dimitrios Sideris, Stamatis F Stamatelopoulos, Spyridon D Moulopoulos
Journal: Journal of the American College of Cardiology (2000)
Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis
Authors: Ejaz Pathan, Sonya Abraham, Elizabeth Van Rossen, Robin Withrington, Andrew Keat, Peter J Charles, Erin Paterson, Muslima Chowdhury, Catherine McClinton, Peter C Taylor
Journal: Annals of the Rheumatic Diseases (2012)

To evaluate the efficacy and safety of an oral phosphodiesterase 4 inhibitor, apremilast, in treatment of ankylosing spondylitis (AS) by monitoring symptoms and signs in a pilot study including exploratory investigation of effects of PDE4 inhibition on blood biomarkers of bone biology.In this double-blind, placebo-controlled, single-centre, Phase II study, patients with symptomatic AS with active disease on MRI were randomised to apremilast 30 mg BID or placebo over 12 weeks. Bath Indices were monitored serially. Patients were followed for 4 weeks after stopping medication. Bone biomarkers were assessed at baseline and day 85.38 subjects were randomised and 36 subjects completed the study. Although the primary end-point (change in BASDAI at week 12) was not met, apremilast was associated with numerically greater improvement from baseline for all clinical assessments compared with placebo with mean change in BASDAI (-1.59±1.48 vs -0.77±1.47), BASFI (-1.74±1.91 vs -0.28±1.61) and BASMI (-0.51±1.02 vs -0.21±0.67); however, differences did not achieve statistical significance. The clinical indices returned to baseline values by 4 weeks after cessation of apremilast. Six apremilast patients (35.3%) vs 3 placebo (15.8%) achieved ASAS20 responses (p=0.25). There were statistically significant decreases in serum RANKL and RANKL:osteoprotegrin ratio and plasma sclerostin but no significant changes in serum DKK-1, bone alkaline phosphatase, TRAP5b, MMP3, osteoprotegrin, or osteocalcin.Although a small pilot study, these results suggest that apremilast may be effective and well tolerated in AS and modulates biomarkers of bone biology. These data support further research of apremilast in axial inflammation.
The Relationship of Psychiatric Disorder to Gastrointestinal Illness
Authors: R E Clouse, D H Alpers
Journal: Annual Review of Medicine (1986)

The definition of psychiatric illness by specific criteria has provided a new method for examining the relationship of certain gastrointestinal (GI) diseases to psychiatric disorder. Using this technique, researchers have found that rates of psychiatric diagnosis in patients with certain functional GI syndromes and Crohn's disease exceed those found in the general population and in comparably ill control groups. Timing of onset of both sets of symptoms (GI and psychiatric) suggests that the functional syndromes generally follow or coincide with the onset of psychiatric symptoms, whereas the onset of Crohn's disease is more independent. A relationship of psychiatric illness to other GI disease is suspected based on results of psychometric testing or on less structured attempts at psychiatric diagnosis employed in earlier studies. Psychiatric diagnosis by criteria definition may play an important role in more clearly understanding any relationship of psychiatric disorder to somatic GI disease as the applications of this scientific technique are expanded.