tbuckley/cabot-search huggingface dataset:
Mitral Annular Dynamics in Myxomatous Valve Disease
Authors: Jasmine Grewal, Rakesh Suri, Sunil Mankad, Akiko Tanaka, Douglas W. Mahoney, Hartzell V. Schaff, Fletcher A. Miller, Maurice Enriquez-Sarano
Journal: Circulation (2010)

Background— Mitral annulus is a complex structure of poorly understood physiology. Full-volume real-time 3-dimensional transesophageal echocardiography offers a unique opportunity to completely image and quantify mitral annulus size and motion. Methods and Results— Real-time 3-dimensional transesophageal echocardiography of the mitral valve was acquired in 32 patients with myxomatous valve disease (MVD) and moderate to severe regurgitation, 15 normal control subjects, and 10 patients with ischemic mitral regurgitation of identical body surface area. Mitral annular dimensions (circumference, area, anteroposterior and intercommissural diameters, height, and ratio of height to intercommissural diameter ratio, which appraises annular saddle-shape depth) were measured throughout the cardiac cycle with dedicated quantification software. Compared with direct surgical measurement, 3-dimensional anterior annular dimension provided reliable measurements (mean difference, 0.1±0.1 mm; P =0.73; 95% confidence interval, ±4.4 mm). Annular dimensions were larger in MVD patients compared with control subjects in diastole (all P &lt;0.05). Normal annulus displayed early-systolic anteroposterior ( P &lt;0.001) and area ( P =0.04) contraction, increased height ( P &lt;0.001), and deeper saddle shape (ratio of height to intercommissural diameter, 15±1% to 21±1%; P &lt;0.001), whereas intercommissural diameter was unchanged ( P =0.30). In contrast, MVD showed early-systolic intercommissural dilatation ( P =0.02) and no area contraction ( P =0.99), height increase ( P =0.11), or saddle-shape deepening ( P =0.35). Late-systolic MVD annular saddle shape deepened but annular area excessively enlarged ( P &lt;0.04) as a result of persistent intercommissural widening ( P &lt;0.02). MVD annulus also contrasts with ischemic mitral regurgitation annulus, which, despite similar anteroposterior enlargement, is narrower and essentially adynamic. After MVD repair, the annulus remained dynamic without systolic saddle-shape accentuation ( P =0.30). Conclusions— Real-time 3-dimensional transesophageal echocardiography provides insights into normal, dynamic mitral annulus function with early-systolic area contraction and saddle-shape deepening contributing to mitral competency. MVD annulus is also dynamic but considerably different with loss of early-systolic area contraction and saddle-shape deepening despite similar magnitude of ventricular contraction, suggestive of ventricular-annular decoupling. Subsequent area enlargement may contribute to mitral incompetence. After mitral repair, MVD annulus remains dynamic without systolic saddle-shape accentuation. Thus, real-time 3-dimensional transesophageal echocardiography provides new insights that allow the refining of mitral pathophysiology concepts and repair strategies.
Graft-versus-host disease after allogeneic hematopoietic stem cell transplantation induces a CD8+ T cell-mediated graft-versus-tumor effect that is independent of the recognition of alloantigenic tumor targets
Authors: Matthias Stelljes, Robert Strothotte, Hans-Gerd Pauels, Christopher Poremba, Michaela Milse, Christiane Specht, Jörn Albring, Guido Bisping, Christian Scheffold, Thomas Kammertoens, Elisabeth Oelmann, Gerda Silling, Wolfgang E. Berdel, Joachim Kienast
Journal: Blood (2004)
G Protein-Coupled Receptor Internalization Signaling Is Required for Cardioprotection in Ischemic Preconditioning
Authors: Haiyan Tong, Howard A. Rockman, Walter J. Koch, Charles Steenbergen, Elizabeth Murphy
Journal: Circulation Research (2004)

The present study is designed to explore the role of G protein-coupled receptors (GPCRs) in the protection afforded by ischemic preconditioning (PC). We used TG mice with cardiac-specific overexpression of a Gbetagamma-sequestering peptide, betaARKct (TG betaARKct mice), to test whether the protection of PC is Gbetagamma-dependent. To test the role of G(i) protein, we used wild-type mice pretreated with the G(i) inhibitor pertussis toxin. Recovery of left ventricular developed pressure and infarct size were measured as indices of protection. PC induced protection in wild-type mice, but this protection was blocked by pertussis toxin treatment and was also blocked in TG betaARKct mice. To determine the mechanism of Gbetagamma-induced protection in PC, we investigated one of the downstream targets of Gbetagamma, the PI3K/p70S6K pathway. PC-induced phosphorylation of p70S6K was not blocked in TG betaARKct hearts; therefore, we investigated other targets of Gbetagamma. Recent studies suggest a role for Gbetagamma in GPCR internalization. We found that betaARKct, a specific PI3K inhibitor wortmannin, and bafilomycin A1, which all block receptor recycling, all blocked the protective effect of PC. To additionally test whether PI3K is involved in PC-activated receptor internalization and endosomal signaling, we used TG mice with cardiac-specific overexpression of a catalytically inactive mutant PI3Kgamma, which disrupts the recruitment of functional PI3K to agonist-activated GPCRs in vivo. We found that the catalytically inactive mutant of PI3Kgamma blocks the protection of PC. In summary, these data suggest the novel finding that the cardioprotective effect of PC requires receptor internalization.
Aldosterone and the heart: towards a physiological function?
Authors: Claude Delcayre, Jean-Sébastien Silvestre
Journal: Cardiovascular Research (1999)

Time for primary review 29 days. 

Aldosterone (Aldo) plays an essential role in regulation of body sodium and potassium homeostasis by acting on epithelial tissues such as kidney and colon. Since about ten years the two dogmas which classically characterize Aldo, i.e., a synthesis in adrenal glands only and an action exclusively in epithelial tissues, have been challenged. Namely, Aldo receptors are present in the heart and specific actions of Aldo can be demonstrated in this organ. This suggests that cardiac tissue may be a genuine target for Aldo. Moreover, there are indications that an increase of plasma Aldo may be a risk factor in cardiovascular pathologies. For example, the CONSENSUS multicentric study has shown a relationship between plasma Aldo concentration and mortality in patients with congestive heart failure [1] The very recent discovery of Aldo synthesis in rat heart [2] brings a new step to the evolution of our ideas concerning the physiology of this hormone. This demonstrates the existence of an Aldo tissular system – i.e., the presence in a cell or a group of cells of all the biochemical elements necessary for synthesis of a hormone and its specific receptors – making it possibly a local autocrine or paracrine action. This review makes the point of the literature dealing with effects and synthesis of Aldo in the heart.

### 2.1 The intracellular mineralo-receptor

Aldo effects are mediated by binding of the hormone to its specific receptor: the mineralocorticoid receptor (MR). The MR is a nuclear zinc-finger transcription factor and forms a subfamily with glucocorticoid receptors (GR), progesterone and androgen receptors. The functional and structural organization of this receptor family displays three main domains: the variable N-terminal region, a well-conserved cysteine-rich DNA-binding domain (=90% amino acid identity) and a C-terminal steroid binding domain (=50% amino acid identity). In addition to epithelial tissues (kidney, … 

* Corresponding author. Tel.: +33-144-631-727; fax: +33-148-742-315 delcayre{at}infobiogen.fr
Conclusive evidence of endotoxaemia in biliary obstruction
Authors: W D B Clements, P Erwin, M D McCaigue, I Halliday, G R Barclay, B J Rowlands
Journal: Gut (1998)

Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA).To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT).Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT.In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; p < 0.001). Although the mean endotoxin concentration in the BDL group was greater than that in the control groups this was not significant. There was a strong positive correlation between ACGA and endotoxin concentrations (p = 0.0021). In the second study mean ACGA after 21 days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at baseline, p < 0.0001). ACGA was unaffected in the other two groups. TT antibody concentrations fell in all three groups; only in the BDL group was the fall significant (97.6 (5.3)% versus 78.8 (4.2)% at baseline, p < 0.05).The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection.
Review: Statins do not increase adverse cognitive effects in patients with or without initial cognitive impairment
Authors: Steven M. Belknap
Journal: Annals of Internal Medicine (2015)

ACP Journal Club19 May 2015Review: Statins do not increase adverse cognitive effects in patients with or without initial cognitive impairmentSteven M. Belknap, MD, FACP, FCPSteven M. Belknap, MD, FACP, FCPNorthwestern University Feinberg School of Medicine, Chicago, Illinois, USA (S.M.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/ACPJC-2015-162-10-006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Source CitationOtt BR, Daiello LA, Dahabreh IJ, et al. Do statins impair cognition? A systematic review and meta-analysis of randomized controlled trials. J Gen Intern Med. 2015;30:348-58. https://pubmed.ncbi.nlm.nih.gov/25575908Clinical Impact RatingsGIM/FP/GP: Mental Health: Cardiology: Geriatrics: Neurology: References1. Swiger KJ, Manalac RJ, Blumenthal RS, Blaha MJ, Martin SS. Statins and cognition: a systematic review and meta-analysis of short- and long-term cognitive effects. Mayo Clin Proc. 2013;88:1213-21. [PMID: 24095248] Google Scholar2. Muldoon MF, Ryan CM, Sereika SM, Flory JD, Manuck SB. Randomized trial of the effects of simvastatin on cognitive functioning in hypercholesterolemic adults. Am J Med. 2004;117:823-9. [PMID: 15589485] Google Scholar3. McDonagh J. Statin-related cognitive impairment in the real world: you'll live longer, but you might not like it. JAMA Intern Med. 2014;174:1889. [PMID: 25347692] Google Scholar4. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther. 1981;30:239-45. [PMID: 7249508] Google Scholar5. Joy TR, Monjed A, Zou GY, et al. N-of-1 (single-patient) trials for statin-related myalgia. Ann Intern Med. 2014;160:301-10. [PMID: 24737272] Google Scholar Author, Article, and Disclosure InformationAffiliations: Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA (S.M.B.)This article was published at Annals.org on 5 May 2015. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 19 May 2015Volume 162, Issue 10Page: JC6KeywordsAlzheimer diseaseCognitionCognitive impairmentDementiaMemoryMini mental state examinationResearch quality assessmentStatinsSystematic reviews ePublished: 19 May 2015 Issue Published: 19 May 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Diabetes Impairs Stem Cell and Proangiogenic Cell Mobilization in Humans
Authors: Gian Paolo Fadini, Mattia Albiero, Saula Vigili de Kreutzenberg, Elisa Boscaro, Roberta Cappellari, Mariacristina Marescotti, Nicol Poncina, Carlo Agostini, Angelo Avogaro
Journal: Diabetes Care (2012)

Diabetes mellitus (DM) increases cardiovascular risk, at least in part, through shortage of vascular regenerative cells derived from the bone marrow (BM). In experimental models, DM causes morphological and functional BM alterations, but information on BM function in human DM is missing. Herein, we sought to assay mobilization of stem and proangiogenic cells in subjects with and without DM.In a prospective trial (NCT01102699), we tested BM responsiveness to 5 μg/kg human recombinant granulocyte colony-stimulating factor (hrG-CSF) in 24 individuals with DM (10 type 1 and 14 type 2) and 14 individuals without DM. Before and 24 h after hrG-CSF, we quantified circulating stem/progenitor cells and total and differential white blood cell counts. We also evaluated in vivo the proangiogenic capacity of peripheral blood mononuclear cells using the Matrigel plug assay.In response to hrG-CSF, levels of CD34(+) cells and other progenitor cell phenotypes increased in subjects without DM. Patients with DM had significantly impaired mobilization of CD34(+), CD133(+), and CD34(+)CD133(+) hematopoietic stem cells and CD133(+)KDR(+) endothelial progenitors, independently of potential confounders. The in vivo angiogenic capacity of peripheral blood mononuclear cells significantly increased after hrG-CSF in control subjects without DM, but not in patients with DM. DM was also associated with the inability to upregulate CD26/DPP-4 on CD34(+) cells, which is required for the mobilizing effect of granulocyte colony-stimulating factor.Stem and proangiogenic cell mobilization in response to hrG-CSF is impaired in DM, possibly because of maladaptive CD26/DPP-4 regulation. These alterations may hamper tissue repair and favor the development of cardiovascular complications.
Patterns of recurrence after initial treatment in patients with small hepatocellular carcinoma
Authors: T Kumada
Journal: Hepatology (1997)

To assess intrahepatic metastasis (IM) and multicentric occurrence (MO) after initial treatment of small hepatocellular carcinomas (HCC) ≦ 2 cm in diameter, we performed clinical and pathological studies in 112 patients who underwent percutaneous ethanol injection therapy (PEIT) or hepatic resection for HCC from January 1985 to December 1994. Patients with intrahepatic recurrences were classified into two groups based on the type of recurrence: the IM group (n = 29, 50.9%) and the MO group (n = 28, 49.1%). Overall recurrence rates after initial treatment were 23.7% at 1 year, 64.5% at 3 years, and 76.1% at 5 years. In patients with IM, the majority of intrahepatic recurrences were observed within 3 years of initial treatment and the primary HCC lesions were closely related to the degree of tumor cell differentiation. Alternatively, intrahepatic recurrences occurred throughout the follow-up period in patients with MO, and the evidence of underlying liver disease (anti-HCV [antibody to hepatitis C virus] positive) and elevated serum alfa-fetoprotein (AFP) concentrations were closely associated with intrahepatic recurrence. Prognoses following additional treatment in MO group patients were superior to those in IM group patients. These results suggest that differentiation between IM and MO in patients with HCC is important for understanding the development and biological behavior of the tumor. That is, the early detection of intrahepatic recurrence and the institution of appropriate additional therapy (PEIT or hepatic resection) may prolong survival in patients with MO.
Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer.
Authors: C L Loprinzi, R M Goldberg, J Q Su, J A Mailliard, S A Kuross, A W Maksymiuk, J W Kugler, J R Jett, C Ghosh, D M Pfeifle
Journal: Journal of Clinical Oncology (1994)

Hydrazine sulfate, an agent that appears to inhibit gluconeogenesis, has been studied in cancer patients for approximately 20 years. There was a recent resurgence of interest in this drug when subset analysis of a small placebo-controlled, double-blind, clinical trial reported improved survival among non-small-cell lung cancer patients with a good performance status who were randomized to receive this drug along with standard chemotherapy.Patients on this trial had newly diagnosed, unresectable non-small-cell lung cancer and were treated with cisplatin and etoposide. In addition, they were randomized to receive hydrazine sulfate or placebo in a double-blind manner.A total of 243 patients were randomized. Response rates were similar in the two treatment arms. There were trends for worse time to progression and survival in the hydrazine sulfate arm. No significant differences were noted in the two study arms with regard to toxicity or quality of life (QL).This trial failed to demonstrate any benefit for patients who received hydrazine sulfate.
Entropy and GC Content in the β-esterase Gene Cluster of the Drosophila melanogaster Subgroup
Authors: Evgeniy S. Balakirev, Vladimir R. Chechetkin, Vasily V. Lobzin, Francisco J. Ayala
Journal: Molecular Biology and Evolution (2005)

We perform spectral entropy and GC content analyses in the β-esterase gene cluster, including the Est-6 gene and the ψEst-6 putative pseudogene, in seven species of the Drosophila melanogaster species subgroup. ψEst-6 combines features of functional and nonfunctional genes. The spectral entropies show distinctly lower structural ordering for ψEst-6 than for Est-6 in all species studied. Our observations agree with previous results for D. melanogaster and provide additional support to our hypothesis that after the duplication event Est-6 retained the esterase-coding function and its role during copulation, while ψEst-6 lost that function but now operates in conjunction with Est-6 as an intergene. Entropy accumulation is not a completely random process for either gene. Structural entropy is nucleotide dependent. The relative normalized deviations for structural entropy are higher for G than for C nucleotides. The entropy values are similar for Est-6 and ψEst-6 in the case of A and T but are lower for Est-6 in the case of G and C. The GC content in synonymous positions is uniformly higher in Est-6 than in ψEst-6, which agrees with the reduced GC content generally observed in pseudogenes and nonfunctional sequences. The observed differences in entropy and GC content reflect an evolutionary shift associated with the process of pseudogenization and subsequent functional divergence of ψEst-6 and Est-6 after the duplication event.
Prediction of relapse with the TRH test and prophylactic amitriptyline in 39 patients with endogenous depression
Authors: I Krog-Meyer, C Kirkegaard, B Kijne, B Lumholtz, E Smith, L Lykke-Olesen, N Bjørum
Journal: American Journal of Psychiatry (1984)

The authors conducted a double-blind prospective study of 39 patients with unipolar endogenous depression who recovered after ECT. Thyrotropin (TSH)-releasing hormone (TRH) tests were performed before and after ECT. Patients were divided into three groups on the basis of their altered TSH response: Persistent remission was predicted for patients in group 1 (N = 15) and relapse was predicted for groups 2A (N = 13) and 2B (N = 11). Patients in groups 1 and 2A received placebo and those in group 2B received amitriptyline for 6 months. Fewer relapses occurred in groups 1 and 2B than in group 2A (p less than .05), showing that relapse can be predicted by the TRH test and prevented by amitriptyline.
9 ASSOCIATION OF A GENETIC VARIANT OF THE TOLL-LIKE RECEPTOR 9 (TLR9) WITH SPONTANEOUS VIRAL CLEARANCE AND WITH INTERFERON RESPONSE IN CHRONIC HEPATITIS C VIRUS INFECTION
Authors: J. Fischer, S. Böhm, D. Deichsel, V. Knop, H. Klinker, B. Möller, J. Rasenack, H. Hinrichsen, U. Spengler, P. Buggisch, C. Sarrazin, T. Berg
Journal: Journal of Hepatology (2013)
Clinical and molecular analysis of patients with defects in μ heavy chain gene
Authors: Eduardo Lopez Granados, Andrea S. Porpiglia, Mary Beth Hogan, Nuria Matamoros, Silvia Krasovec, Claudio Pignata, C.I.E. Smith, Lennart Hammarstrom, Janne Bjorkander, Bernd H. Belohradsky, G. Fontan Casariego, M.C. Garcia Rodriguez, Mary Ellen Conley
Journal: Journal of Clinical Investigation (2002)

Autosomal recessive disorders of B cell development are rare and heterogeneous. To determine the proportion of affected patients who have defects in the μ heavy chain (IGHM) gene, we used single-stranded conformational polymorphism analysis to screen genomic DNA from 40 unrelated patients with early onset infections, profound hypogammaglobulinemia, and absent B cells. All of the patients were genotypically normal in BTK, the gene that underlies X-linked agammaglobulinemia. Eight different mutations in the μ heavy chain were identified in 19 members of 12 unrelated families. Four of the mutations were large deletions that removed more than 40 kb of DNA in the IGHM locus. In six of the 12 families, the affected patients had an identical single base pair substitution, a G→A, at the –1 position of the alternative splice site. Immunoglobulin haplotype analysis showed that this mutation occurred on at least three different haplotypes, indicating that this is a hot spot for mutations. Compared with patients with mutations in Btk, patients with defects in the μ heavy chain had an earlier onset of disease and more complications. Our study indicates that at least 20–30% of patients with autosomal recessive defects in B cell development have mutations in the μ heavy chain.
Reduced glenohumeral rotation, external rotation weakness and scapular dyskinesis are risk factors for shoulder injuries among elite male handball players: a prospective cohort study
Authors: Benjamin Clarsen, Roald Bahr, Stig Haugsboe Andersson, Rikke Munk, Grethe Myklebust
Journal: British Journal of Sports Medicine (2014)

Aim To determine whether rotator cuff strength, glenohumeral joint range of motion and scapular control are associated with shoulder injuries among elite male handball players. Methods A total of 206 players in the Norwegian elite handball league for men were tested prior to the 2011–2012 season. Measures included: (1) glenohumeral internal and external rotation range of motion, (2) isometric internal rotation, external rotation and abduction strength and (3) assessment of scapular dyskinesis. Players were followed prospectively for the entire regular season (30 weeks), with shoulder problems registered bi-weekly using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. A cumulative severity score was calculated for each player based on their questionnaire responses. This was used as the outcome measure in risk factor analyses. Results The average prevalence of shoulder problems throughout the season was 28% (95% CI 25% to 31%). The prevalence of substantial shoulder problems, defined as those leading to moderate or severe reductions in handball participation or performance, or to time loss, was 12% (95% CI 11% to 13%). Significant associations were found between obvious scapular dyskinesis (OR 8.41, 95% CI 1.47 to 48.1, p&lt;0.05), total rotational motion (OR 0.77 per 5° change, 95% CI 0.56 to 0.995, p&lt;0.05) and external rotation strength (OR 0.71 per 10 Nm change, 95% CI 0.44 to 0.99, p&lt;0.05) and shoulder injury. Conclusions Injury prevention programmes should incorporate interventions aimed at improving glenohumeral rotational range of motion, external rotation strength and scapular control.