tbuckley/cabot-search huggingface dataset:
Importance of Mitral Valve Repair Associated With Left Ventricular Reconstruction for Patients With Ischemic Cardiomyopathy: A Real-Time Three-Dimensional Echocardiographic Study
Authors: Jian Xin Qin, Takahiro Shiota, Patrick M. McCarthy, Craig R. Asher, Melanie Hail, Deborah A. Agler, Zoran B. Popović, Neil L. Greenberg, Nicholas G. Smedira, Randall C. Starling, James B. Young, James D. Thomas
Journal: Circulation (2003)

Left ventricular (LV) reconstruction surgery leads to early improvement in LV function in ischemic cardiomyopathy (ICM) patients. This study was designed to evaluate the impact of mitral valve (MV) repair associated with LV reconstruction on LV function 1-year after surgery in ICM patients assessed by real-time 3-dimensional echocardiography (3DE).Sixty ICM patients who underwent the combination surgery (LV reconstruction in 60, MV repair in 30, and revascularization in 52 patients) were studied. Real-time 3DE was performed and LV volumes were obtained at baseline, discharge, 6-month and >or=12-month follow-up. Reduction in end-diastolic volumes (EDV) by 29% and in end-systolic volumes by 38% were demonstrated immediately after surgery and remained at subsequent follow-up (P<0.0001). The LV ejection fraction significantly increased by about 10% at discharge and was maintained >or=12-month (P<0.0001). Although the LV volumes were significantly larger in patients with MV repair before surgery (EDV, 235+/-87 mL versus 193+/-67 mL, P<0.05), they were similar to LV volumes of the patients without MV repair at subsequent follow-ups. However, the EDV increased from 139+/-24 mL to 227+/-79 mL (P<0.01) in 7 patients with recurrent mitral regurgitation (MR). Improvement in New York Heart Association functional class occurred in 81% patients during late follow-up.Real-time 3DE demonstrates that LV reconstruction provides significant reduction in LV volumes and improvement in LV function which is sustained throughout the 1-year follow-up with 84% cardiac event free survival. If successful, MV repair may prevent LV redilation, while recurrent MR is associated with increased LV volumes.
Hepatic gene induction in murine bone marrow after hepatectomy
Authors: Shintaro Yamazaki, Kenji Miki, Tadatoshi Takayama, Kiyoshi Hasegawa, Masataka Sata, Yutaka Midorikawa, Hiroyuki Aburatani, Masatoshi Makuuchi
Journal: Journal of Hepatology (2005)
WHO to probe claims that Dutch scientists restricted access to novel coronavirus
Authors: C. D. O. Dyer
Journal: BMJ (2013)

The World Health Organization is to investigate claims by Saudi Arabia that a Dutch laboratory’s patenting of a novel coronavirus variant is hindering research into the pathogen that has claimed 23 lives in several countries.

Saudi deputy health minister Ziad Memish told the World Health Assembly last week that samples of the Middle East respiratory syndrome (MERS) coronavirus, which first emerged in his country, had been sent abroad without permission. “We are still struggling with diagnostics and the reason is that the virus was patented by scientists and is not allowed to be used for investigations by other scientists,” he said.

WHO director general Margaret Chan promised to “look at the legal implications together with the Kingdom of Saudi Arabia.” She added: “No IP [intellectual property] should stand in the way of you, the countries of the world, to protect your …
Antibodies to citrullinated α-enolase peptide 1 and clinical and radiological outcomes in rheumatoid arthritis
Authors: Benjamin A Fisher, Darren Plant, Monica Brode, Ronald F van Vollenhoven, Linda Mathsson, Deborah Symmons, Karin Lundberg, Johan Rönnelid, Patrick J Venables
Journal: Annals of the Rheumatic Diseases (2011)

Introduction The anticyclic citrullinated peptide 2 (anti-CCP2) assay is a generic test for antibodies to citrullinated proteins, among which there is a subset of about 50% with antibodies to citrullinated enolase peptide 1 (CEP-1). The anti-CEP-1 positive subset is strongly associated with the HLA-DRB1 shared epitope and its interaction with smoking. Objective To investigate whether anti-CEP-1 antibodies may be helpful in predicting outcome. Methods Anti-CEP-1 and anti-CCP2 antibodies were measured in two prospective cohorts of patients (Karolinska n=272, Norfolk Arthritis Register (NOAR) n=408) with early rheumatoid arthritis (RA). Outcomes measured were C-reactive protein, erythrocyte sedimentation rate, visual analogue scales for pain and global assessment of disease activity, Health Assessment Questionnaire, physician's assessment, swollen and tender joint counts and radiological progression. Results Anti-CCP2 antibodies were present in 57% and 50%, and anti-CEP-1 in 27% and 24% of the Karolinska and NOAR cohorts, respectively. Importantly, no statistically significant differences in clinical outcomes were demonstrated between the anti-CEP-1−/CCP2+ and the anti-CEP-1+/CCP2+ subsets in either cohort, or in radiological outcomes in the Karolinska cohort. Conclusion Although antibodies to specific citrullinated proteins may have distinct genetic and environmental risk factors, the similarity in clinical phenotype suggests that they share common pathways in the pathogenesis of joint disease in RA.
Protective effect of a microtubule stabilizer taxol on caerulein-induced acute pancreatitis in rat.
Authors: T Ueda, Y Takeyama, K Kaneda, M Adachi, H Ohyanagi, Y Saitoh
Journal: Journal of Clinical Investigation (1992)

The effect of taxol, which is a microtubule stabilizer, was examined in a model of acute edematous pancreatitis induced in rat by the administration of caerulein. Prophylactic administration of taxol ameliorated inhibition of pancreatic secretion, increased level of serum amylase, pancreatic edema, and histological alterations in this model. Immunofluorescence studies revealed that taxol stabilized the arrangement of microtubules by the action of promoting tubulin polymerization and prevented inhibition of pancreatic digestive enzyme secretion. In isolated rat pancreatic acini, taxol reversed the inhibition of amylase secretion induced by supramaximal concentrations of cholecystokinin octapeptide and did not affect the binding of cholecystokinin octapeptide to its receptor. The results obtained in this study suggest that microtubule disorganization is the initiating event in caerulein-induced pancreatitis and that the inhibition of pancreatic digestive enzyme secretion by interfering with intracellular vesicular transport due to microtubule disorganization causes caerulein-induced pancreatitis.
The association of bone attrition with knee pain and other MRI features of osteoarthritis
Authors: G Hernandez-Molina, T Neogi, D J Hunter, J Niu, A Guermazi, S Reichenbach, F W Roemer, C E McLennan, D T Felson
Journal: Annals of the Rheumatic Diseases (2007)

<h3>Objective:</h3> To determine whether bone attrition (flattening or depression of the subchondral bone) was associated with the presence and severity of knee pain and to evaluate the coexistence of attrition and other MRI features likely associated with pain. <h3>Methods:</h3> Participants in the Framingham Osteoarthritis Study, a community cohort unselected for OA, answered questions about knee pain and underwent knee <i>x</i> rays and MRI. Attrition, bone marrow lesions (BMLs) and effusions were scored on MRI using the WORMS scale. We assessed attrition in knees with and without pain, and using logistic regression examined its association with pain adjusting for age, gender, Kellgren–Lawrence (K–L) grade, BMI, BML and effusion. We also explored the relation between attrition, pain severity and nocturnal pain. <h3>Results:</h3> Attrition (Grade ⩾2) was present in 28% (167/592) of painful knees and in 10% (106/1035) of non-painful knees (adjusted OR 1.6 (95% CI 1.1 to 2.2)). Of knees with OA (n = 368), 74% had pain if attrition was present and 58% if it was absent (adjusted OR 1.2 (95% CI 0.7 to 2.0)). Of knees without OA (n = 1222), pain was reported in 39% of knees with attrition and in 27% without it (adjusted OR 2.1 (95% CI 1.1 to 4.0)). We found no association between either attrition/pain severity or attrition/nocturnal pain. Attrition often co-occurred with other OA features associated with pain such as BMLs and effusions. <h3>Conclusions:</h3> Attrition was associated independently with knee pain. Unlike knees without OA, the association was lost in OA knees where other pathological features that may cause pain also coexisted.
Analysis of hepatic T lymphocyte and immunoglobulin deposits in patients with primary biliary cirrhosis
Authors: Sheri M. Krams, Judy van de Water, Ross L. Coppel, Carlos Esquivel, John Roberts, Aftab Ansari, M. Eric Gershwin
Journal: Hepatology (1990)

The histological findings in patients with primary biiary cirrhosis have been well-defined and are often used in the clinical staging of disease. However, it has only been with the development of reagents that phenotypically characterize the lymphoid infiltrate that attempts have been made to correlate pathophysiology with immune effector populations. Indeed, the inflammatory hepatic lesions in primary biliary cirrhosis have been described as containing CD4-positive and CD8-positive T cells. Less clear, however, have been the T cell receptors in these lesions. Further, the data on immunoglobulin deposits in hepatic lesions have been less well-defined; this deficit may be a result of the quality of polyspecific sera and difficulties in background. To address these issues, we have used a battery of well-defined monospecific and polyspecific reagents to phenotypically define the occurrence of lymphoid cells in the livers of patients undergoing transplantation. Furthermore, we have defined these same markers on T cell lines derived from liver, regional lymph node and peripheral blood. The predominant cell type in the mononuclear infiltrate is the CD3+, CD4+ T lymphocyte bearing the T cell receptor αβ. T cell lines from the same patients demonstrate similar findings. Of special importance, however, was the detection of CD20+ B cells and Ig+ cells in the lymphoid infiltrate. Indeed, we also readily demonstrated the presence of immunoglobulin on the surface of biliary epithelium. These data suggest that mechanisms involved in the pathophysiology of primary biliary cirrhosis may include both T cell and antibody mechanisms. The results also underscore the need to develop a functional, and not just a phenotypical, assay of the inflammatory infiltrate. (HEPATOLOGY 1990;12:306–313).
Low doses of isosorbide mononitrate attenuate the postprandial increase in portal pressure in patients with cirrhosis
Authors: Lia Bellis, Annalisa Berzigotti, Juan G. Abraldes, Eduardo Moitinho, Juan C. García-Pagán, Jaime Bosch, Juan Rodés
Journal: Hepatology (2003)

Postprandial hyperemia is associated with a significant increase in portal pressure in cirrhosis, which may contribute to progressive dilation and rupture of gastroesophageal varices. In cirrhosis, an insufficient hepatic production of nitric oxide (NO) may impair the expected hepatic vasodilatory response to increased blood flow, further exaggerating the postprandial increase in portal pressure. This study was aimed at investigating whether low doses of an oral NO donor might counteract the postprandial peak in portal pressure. Twenty-three portal hypertensive cirrhotics, 8 of them under propranolol therapy, were randomized to receive orally 5-isosorbide mononitrate (ISMN; 10 mg; n = 11) or placebo (n = 12) and a standard liquid meal 15 minutes later. Hepatic venous pressure gradient (HVPG), mean arterial pressure (MAP), and hepatic blood flow (HBF) were measured at baseline and 15, 30, and 45 minutes after a meal. ISMN significantly attenuated the postprandial increase in portal pressure as compared with placebo (peak HVPG increase: 2.4 ± 1.4 mm Hg vs. 5.2 ± 2.1 mm Hg, P = .002). Percentual increases in HBF were similar in both groups. MAP decreased slightly in ISMN group (−7.5% ± .5%; P &lt; .01 vs. baseline). These effects were also observed in patients on chronic propranolol therapy. In conclusion, hepatic NO supplementation by low doses of ISMN effectively reduces the postprandial increase of portal pressure in cirrhosis, with only a mild effect on arterial pressure. The same was observed in patients receiving propranolol. Our results suggest that therapeutic strategies based on selective hepatic NO delivery may improve the treatment of portal hypertension.
Pregnancy and the Prolactin Family of Hormones: Coordination of Anterior Pituitary, Uterine, and Placental Expression*
Authors: MICHAEL J. SOARES, TERESA N. FARIA, KATHERINE F. ROBY, SANTANU DEB
Journal: Endocrine Reviews (1991)

SPECIALIZED strategies have evolved for controlling embryonic development. In oviparous species, development of the embryo is dependent upon regulatory factors contained within the egg, whereas embryonic development in mammalian species and some nonmammalian species, viviparity, is more complex, requiring regulatory factors arising from maternal, extraembryonic, and embryonic tissues. Successful maturation of the mammalian embryo is largely dependent upon the functioning of a specialized extraembryonic tissue of pregnancy, the placenta. The placenta is a tissue that develops in concert with the embryo and enables the embryo to have access to and to control the availability of maternal resources. Several essential functions are performed by the placenta: 1) regulation of nutrient and waste transport between maternal and fetal compartments, 2) immunological modulation, preventing rejection of the genetically disparate embryo, and 3) transduction of fetal and maternal signals.
Effect of statins on endothelial dysfunction in patients with chronic obstructive pulmonary disease and metabolic syndrome
Authors: Anastasya Stupnytska, Ganna Stupnytska
Journal: European Respiratory Journal (2014)

Metabolic disease and heart disease are the two most frequent disease combinations with chronic obstructive pulmonary disease (COPD). Endothelial dysfunction and systemic inflammation is an essential component of COPD and metabolic syndrome (MS), which mechanisms of developementand the possibility of pharmacological correctionare studying by scientists.  Objective: To study the effect of statins on endothelial dysfunction in patients with COPD and MS.  Methods. The study involved 33 patients with COPD on second and third stages with MS. Atorvastatin was administered 10 mg once per day for 6 months. The functional state of the endothelium was studied by blood levels of stable metabolites NO (nitrite, nitrate) by Green LC et al, endothelin-1 and the number of circulating desquamatedendothelial cells in blood. Processing of the results was performed using the analysis package in Microsoft Excel program and SPSS 11.0.  Results. Combined treatment with the addition of statin to the therapy schemes causedincreasingof stable metabolitesNO in blood (36%) against a statistically significant reduction in serum ET- 1 (34 %) and decreasing the number of desquamated endothelial cells in blood (28%) of high degree of confidence.  Conclusions. Thus, the decrease of endothelial dysfunction could occur due to the partial removal of the vascular wall inflammation, due to pleiotropic effects of atorvastatin.
Evolutionary Change of the Numbers of Homeobox Genes in Bilateral Animals
Authors: Jongmin Nam, Masatoshi Nei
Journal: Molecular Biology and Evolution (2005)

It has been known that the conservation or diversity of homeobox genes is responsible for the similarity and variability of some of the morphological or physiological characters among different organisms. To gain some insights into the evolutionary pattern of homeobox genes in bilateral animals, we studied the change of the numbers of these genes during the evolution of bilateral animals. We analyzed 2,031 homeodomain sequences compiled from 11 species of bilateral animals ranging from Caenorhabditis elegans to humans. Our phylogenetic analysis using a modified reconciled-tree method suggested that there were at least about 88 homeobox genes in the common ancestor of bilateral animals. About 50–60 genes of them have left at least one descendant gene in each of the 11 species studied, suggesting that about 30–40 genes were lost in a lineage-specific manner. Although similar numbers of ancestral genes have survived in each species, vertebrate lineages gained many more genes by duplication than invertebrate lineages, resulting in more than 200 homeobox genes in vertebrates and about 100 in invertebrates. After these gene duplications, a substantial number of old duplicate genes have also been lost in each lineage. Because many old duplicate genes were lost, it is likely that lost genes had already been differentiated from other groups of genes at the time of gene loss. We conclude that both gain and loss of homeobox genes were important for the evolutionary change of phenotypic characters in bilateral animals.
Phase II trial of weekly bortezomib in combination with rituximab in untreated patients with Waldenström Macroglobulinemia
Authors: Irene M. Ghobrial, Wanling Xie, Swaminathan Padmanabhan, Ashraf Badros, Meghan Rourke, Renee Leduc, Stacey Chuma, Janet Kunsman, Diane Warren, Tiffany Poon, Brianna Harris, Amy Sam, Kenneth C. Anderson, Paul G. Richardson, Steven P. Treon, Edie Weller, Jeffrey Matous
Journal: American Journal of Hematology (2010)

This study aimed to determine the activity and safety of weekly bortezomib and rituximab in patients with untreated Waldenström Macroglobulinemia (WM). Patients with no prior therapy and symptomatic disease were eligible. Patients received bortezomib IV weekly at 1.6 mg/m(2) on days 1, 8, 15, q 28 days × 6 cycles, and rituximab 375 mg/m(2) weekly on cycles 1 and 4. Primary endpoint was the percent of patients with at least a minor response (MR). Twenty-six patients were treated. At least MR was observed in 23/26 patients (88%) (95% CI: 70-98%) with 1 complete response (4%), 1 near-complete response (4%), 15 partial remission (58%), and 6 MR (23%). Using IgM response evaluated by nephlometry, all 26 patients (100%) achieved at least MR or better. The median time to progression has not been reached, with an estimated 1-year event free rate of 79% (95% CI: 53, 91%). Common grade 3 and 4 therapy related adverse events included reversible neutropenia in 12%, anemia in 8%, and thrombocytopenia in 8%. No grade 3 or 4 neuropathy occurred. The combination of weekly bortezomib and rituximab exhibited significant activity and minimal neurological toxicity in patients with untreated WM.
Concerns about immunisation
Authors: H. Bedford
Journal: BMJ (2000)

<h3>Background</h3> Cardiac sarcoidosis (CS) is a life-threatening condition in which clear recommendations are lacking. We aimed to review systematically the literature on cardiac sarcoidosis treated by corticosteroids and/or immunosuppressive agents in order to update the management of CS. <h3>Methods</h3> Using Pubmed, Embase and Cochrane Library databases, we found original articles on corticosteroid and/or standard immunosuppressive therapies for CS which provided at least fair SIGN overall assessment of quality and analyse the relapse rate, major cardiac adverse events (MACEs) and adverse events. We base our methods on Prisma statement and checklist. <h3>Results</h3> We retrieved 21 studies. Mean quality provided by SIGN assessment was 6.8/14 (range 5–9). Corticosteroids appeared to have a positive impact on left ventricular function, atrioventricular block, and ventricular arrhythmias. For corticosteroids alone, nine (45%) studies (n=351) provided data on relapses, representing an incidence of 34% (n=119). Three studies (14%, n=73) provided data on MACEs (n=33), representing 45% of MACEs in patients treated by corticosteroid alone. Nine studies provided data on adjunctive immunosuppressive therapy in which four studies (n=78) provided data on CS relapse, representing an incidence of 33% (n=26). Limitations consisted in no randomised control trial retrieved and unclear data on MACEs in patients treated by combined immunosuppressive agents and corticosteroids. <h3>Conclusions</h3> Corticosteroids should be started early after diagnosis but the exact scheme is still unclear. Studies concerning adjunctive conventional immunosuppressive therapies are lacking and benefits of adjunctive immunosuppressive therapies are unclear. Homogenous data on CS long-term outcomes under corticosteroids, immunosuppressive therapies and other adjunctive therapies are lacking.
An miR-502–Binding Site Single-Nucleotide Polymorphism in the 3′-Untranslated Region of the <i>SET8</i> Gene Is Associated with Early Age of Breast Cancer Onset
Authors: Fengju Song, Hong Zheng, Ben Liu, Sheng Wei, Hongji Dai, Lina Zhang, George A. Calin, Xishan Hao, Qingyi Wei, Wei Zhang, Kexin Chen
Journal: Clinical Cancer Research (2009)

Abstract Purpose: MicroRNAs regulate gene expression by binding to the 3′-untranslated region (UTR) of target genes. Single-nucleotide polymorphisms of critical genes may affect their regulation by microRNAs. We have identified a single-nucleotide polymorphism within the miR-502 seed binding region in the 3′-UTR of the SET8 gene. SET8 methylates TP53 and regulates genome stability. We investigated the role of this SET8 single-nucleotide polymorphism and in concert with the TP53 codon 72 single-nucleotide polymorphism in the propensity for onset of breast cancer. Experimental Design: We measured the SET8 single-nucleotide polymorphisms in a case-control study on 1,110 breast cancer cases and 1,097 controls. Results: The SET8 CC and TP53 GG genotypes were independently associated with an earlier age of breast cancer onset in an allele-dose-dependent manner (for SET8, 52.2 years for TT, 51.4 for TC, and 49.5 for CC; and for TP53, 53.1 years for CC, 51.5 for GC, 50.7 for GG). Individuals with combined SET8 CC and TP53 GG genotypes developed cancer at a median age of 47.7 years as compared with 54.6 years for individuals with combined SET8 TT and TP53 CC genotypes. In the 51 breast cancer tissue samples tested, the SET8 CC genotype was associated with reduced SET8, but not miR-502, transcript levels. Conclusions: These data suggest that the miR-502–binding site single-nucleotide polymorphism in the 3′-UTR of SET8 modulates SET8 expression and contributes to the early development of breast cancer, either independently or together with the TP53 codon 72 single-nucleotide polymorphism. Larger studies with multiethnic groups are warranted to validate our findings. (Clin Cancer Res 2009;15(19):6292–300)