tbuckley/cabot-search huggingface dataset:
The dexamethasone suppression test in the clinical setting
Authors: Evans Dl, Burnett Gb, Nemeroff Cb
Journal: American Journal of Psychiatry (1983)

The authors administered the dexamethasone suppression test (DST) to 47 inpatients on a clinical, nonresearch psychiatric unit who had been diagnosed according to DSM-III. Of the 30 patients with major depression, 23 (77%) exhibited nonsuppression (serum cortisol concentrations greater than 5 micrograms/dl); only 1 of the 17 patients with other diagnoses and depressive symptoms exhibited nonsuppression. There was no difference in the rate of nonsuppression between the patients with subgroups of major depression, but those with major depression and psychosis had significantly higher postdexamethasone cortisol levels than those with major depression with and without melancholia and those with diagnoses other than major depression.
Platelet activation markers overexpressed specifically in patients with aspirin-exacerbated respiratory disease
Authors: Chihiro Mitsui, Keiichi Kajiwara, Hiroaki Hayashi, Jun Ito, Haruhisa Mita, Emiko Ono, Noritaka Higashi, Yuma Fukutomi, Kiyoshi Sekiya, Takahiro Tsuburai, Kazuo Akiyama, Kazuhiko Yamamoto, Masami Taniguchi
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract B44: The histone deacetylase SIRT6 regulates metabolism in pancreatic ductal adenocarcinoma
Authors: Sita Kugel, Carlos Sebastián, Rushika M. Perera, Nabeel Bardeesy, Raul Mostoslavsky
Journal: Cancer Research (2015)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer death and one of the most aggressive and deadly malignancies, with limited therapeutic options. Sirtuin 6 (SIRT6) is a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase that functions as a novel tumor suppressor, which regulates aerobic glycolysis in cancer cells. Whether glycolysis plays a role in pancreatic cancer development remains a topic of intense study. Importantly, we found SIRT6 to be downregulated in human PDAC and most pancreatic cancer cell lines, resulting in increased expression of glycolytic genes. To determine the role of SIRT6 in pancreatic cancer we utilized human PDAC cell lines that demonstrated low expression of SIRT6 compared to a human pancreatic ductal epithelial (HPDE) control cell line. Restoration of SIRT6 expression decreased the levels of glycolytic gene expression, reduced glucose uptake, and inhibited cell growth. Conversely, knockdown of SIRT6 in HPDE cells increased glycolytic gene expression, glucose uptake and enhanced cell growth. To further explore the role of SIRT6 in a genetically defined PDAC model, we used an autochthonous mouse model with conditional alleles for KRASG12D, p53, and SIRT6, together with a p48-Cre allele to delete SIRT6 and p53 while expressing oncogenic Ras exclusively in the pancreas. SIRT6null, KRASG12D, p53+/- p48 tumor cells also exhibited increased expression of glycolytic genes and had enhanced glucose uptake compared to SIRT6+/+, KRASG12D, p53+/- p48 tumor cells, a phenotype which is reversed by restoration of wild-type but not catalytically inactive SIRT6 expression. Understanding how SIRT6 regulates PDAC metabolism through the modulation of chromatin dynamics will hopefully lead to new therapies to tackle aberrant metabolism in this devastating disease. Citation Format: Sita Kugel, Carlos Sebastián, Rushika M. Perera, Nabeel Bardeesy, Raul Mostoslavsky. The histone deacetylase SIRT6 regulates metabolism in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B44.
Abstract 4151: Relation of Specific Urinary Amino Acids to Blood Pressure: Findings from the INTERMAP Study
Authors: Martha L Daviglus, Jeremiah Stamler, Lucila Blanco-Cedres, Paul Elliott, Hugo Kesteloot, Peter Declercq, Queenie Chan, Ka He, Daniel B Garside, Xuan Cai, Hirotsugu Ueshima, Beifan Zhou, Alan R Dyer
Journal: Circulation (2006)
Suppressed expression of miR-378 targeting gzmb in NK cells is required to control dengue virus infection
Authors: Shuyan Liu, Lingming Chen, Ying Zeng, Lulu Si, Xiaolan Guo, Junmei Zhou, Danyun Fang, Gucheng Zeng, Lifang Jiang
Journal: Cellular and Molecular Immunology (2015)

Dengue virus (DENV) remains a major public health threat because no vaccine or drugs are available for the prevention and treatment of DENV infection, and the immunopathogenesis mechanisms of DENV infection are not fully understood. Cytotoxic molecules, such as granzyme B (GrzB), may be necessary to control viral infections. However, the exact role of GrzB during DENV infection and the mechanisms regulating GrzB expression during DENV infection are not clear. This study found that miR-27a*, miR-30e, and miR-378 were down-regulated in DENV-infected patients, and DENV infection in humans induced a significant up-regulation of GrzB in natural killer (NK) cells and CD8+ T cells. Further investigation indicated that NK cells, but not CD8+ T cells, were the major sources of GrzB, and miR-378, but not miR-27a* or miR-30e, suppressed GrzB expression in NK cells. Notably, we found that overexpression of miR-378 using a miR-378 agomir in DENV-infected mice inhibited GrzB expression and promoted DENV replication. These results suggest the critical importance of miR-378 in the regulation of GrzB expression and a protective role for GrzB in controlling DENV replication in vivo. Therefore, this study provides a new insight into the immunopathogenesis mechanism of DENV infection and a biological basis for the development of new therapeutic strategies to control DENV infection.
Therapeutic effect of anti CEACAM6 monoclonal antibody against lung adenocarcinoma by enhancing anoikis sensitivity
Authors: Kwon Pyo Hong, Mi Hyang Shin, SangSoon Yoon, Gil Yong Ji, Yoo Ri Moon, Ok-Jun Lee, Song-Yi Choi, Yong-Moon Lee, Ji Hae Koo, Ho-Chang Lee, Geon Kook Lee, Seung Ryul Kim, Ki Hyeong Lee, Hye-Suk Han, Kang Hyeon Choe, Ki Man Lee, Jong-Myeon Hong, Si-Wook Kim, Jae Hyuk Yi, Hyeong-Jin Ji, Yun-Bae Kim, Hyung Geun Song
Journal: Biomaterials (2015)

Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) plays a crucial role in tumorigenesis of lung cancer. However, the therapeutic potential for anti CEACAM6 monoclonal antibody (mAb) has only been limitedly explored. Here, we evaluate the therapeutic potential of naked anti CEACAM6 mAb against lung adenocarcinoma. Clone 8F5, recognizing B domain of CEACAM6, is established by immunizing A549 cells and screening for clones double positive for A549 and CEACAM6-Fc recombinant protein. We found that 85.7% of 70 resected lung adenocarcinoma tissue sections were positive for CEACAM6, whereas all squamous cell carcinoma examined were negative. A549 cells with high levels of CEACAM6 demonstrated more aggressive growth nature and showed increased paclitaxel chemosensitivity upon 8F5 binding. Treatment with 8F5 to A549 decreased cellular CEACAM6 expression and reversed anoikis resistance. 8F5 also decreased cellular status of Akt phosphorylation and increased apoptosis via caspase activation. In a mouse model of lung adenocarcinoma with xenotransplanted A549 cells, 8F5 treatment alone demonstrated 40% tumor growth inhibition. When combined with paclitaxel treatment, 8F5 markedly enhanced tumor growth inhibition, up to 80%. In summary, we demonstrate that anti CEACAM6 mAb is an effective therapeutic treatment for lung adenocarcinoma whose effect is further enhanced by combined treatment with paclitaxel.
Abstract 2830: Additional Value of Myocardial Perfusion Imaging during Dobutamine Stress Magnetic Resonance for the Assessment of Coronary Artery Disease
Authors: Rolf Gebker, Cosima Jahnke, Robert Manka, Ashraf Hamdan, Bernhard Schnackenburg, Eckart Fleck, Ingo Paetsch
Journal: Circulation (2008)

Background: Dobutamine stress magnetic resonance (DSMR) imaging has emerged as a valuable tool for the detection of inducible wall motion abnormalities (WMA). The role of perfusion imaging during DSMR is not well defined. We examined whether the addition of myocardial perfusion imaging during DSMR provides incremental benefit for the evaluation of coronary artery disease (CAD). Methods and Results: DSMR was combined with perfusion imaging (DSMRP) in 455 consecutive patients who were scheduled for clinically indicated invasive coronary angiography. Perfusion images were acquired in three standard short axis views at rest and during maximum dobutamine-atropine stress. Wall motion and perfusion images were interpreted sequentially, blinded to other data. Significant (≥70%) stenoses were present in 285 patients in invasive coronary angiography. For the overall population the addition of perfusion imaging improved sensitivity for the detection of CAD (91% versus 85%, P=0.001) with a significant reduction in specificity (70% vs. 82%, P=0.001) and no difference in diagnostic accuracy (84% vs. 84%, P n.s.). DSMRP enabled the correct diagnosis of CAD in an additional 13% of patients. DSMRP enhanced diagnostic accuracy in patients with left ventricular hypertrophy (LVH) (87% vs. 80%, P&lt;0.001), resting WMAs (84% vs. 80%, P&lt;0.001), prior CAD (85% vs. 82%, P&lt;0.001) and it improved sensitivity in patients with single vessel disease (91% vs. 84%, P&lt;0.001). Conclusion: The addition of perfusion imaging during DSMR is a useful technique for the diagnosis of CAD and adds additional diagnostic value in patients with LVH, resting WMAs, prior CAD and single-vessel disease.
Abstract 9834: Impact of Bone Marrow Cell Therapy on Left Ventricular Function, Structure, and Clinical Outcomes in Patients with Ischemic Heart Disease: A Meta-Analysis
Authors: Vinodh Jeevanantham, Matthew Butler, Andre Saad, Ahmed Abdel-Latif, Buddhadeb Dawn
Journal: Circulation (2011)

Background: The effects of adult bone marrow cell (BMC) therapy on left ventricular (LV) function, remodeling, and clinical outcomes in patients with ischemic heart disease (IHD) remain controversial. We systematically reviewed the effects of BMC therapy on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct size, and clinical outcomes in patients with IHD. Methods: We searched the MEDLINE, Web of Science, Cochrane Central Register of Controlled Trials, and reference lists of retrieved articles for relevant clinical trials through March 2010. Randomized control trials (RCTs) and cohort studies conducted in patients with IHD were included. Weighted Mean Difference (WMD) for changes in LVEF, LVESV, LVEDV and infarct size were estimated using random effects meta-analysis. Peto odds ratio was calculated for clinical outcomes. Results: A total of 43 studies (enrolling 2,537 patients) out of 1,554 identified studies were included in the final analysis. Compared with the standard treatment group, BMC-treated patients showed a significant increase in LVEF, and significant decrease in LVESV, LVEDV, and infarct size (Table). These findings were significant irrespective of the study design (RCTs vs. Cohort studies), type of IHD (acute myocardial infarction vs. chronic IHD) and duration of follow up. Compared with patients who received standard therapy, BMC-treated patients showed significant decrease in all-cause mortality, cardiac mortality, recurrent MI, and stent thrombosis (Table). Conclusions: The pooled data from this largest meta-analysis of its kind to date show that compared with standard therapy, transplantation of adult BMCs results in significant improvement in LV structure, function and scar size in patients with IHD. In addition, BMC therapy is associated with significant reduction in mortality, recurrent MI and stent thrombosis compared to standard therapy in patients with IHD.
Detection of colorectal polyps in humans using an intravenously administered fluorescent peptide targeted against c-Met
Authors: Jacobus Burggraaf, Ingrid M C Kamerling, Paul B Gordon, Lenneke Schrier, Marieke L de Kam, Andrea J Kales, Ragnar Bendiksen, Bård Indrevoll, Roger M Bjerke, Siver A Moestue, Siavash Yazdanfar, Alexandra M J Langers, Marit Swaerd-Nordmo, Geir Torheim, Madhuri V Warren, Hans Morreau, Philip W Voorneveld, Tessa Buckle, Fijs W B van Leeuwen, Liv-Ingrid Ødegårdstuen, Grethe T Dalsgaard, Andrew Healey, James C H Hardwick
Journal: Nature Medicine (2015)
Transapical Aortic Valve Implantation in 175 Consecutive Patients
Authors: Miralem Pasic, Axel Unbehaun, Stephan Dreysse, Thorsten Drews, Semih Buz, Marian Kukucka, Alexander Mladenow, Tom Gromann, Roland Hetzer
Journal: Journal of the American College of Cardiology (2010)
Abstract 2565: Predictors For Very Late Stent Thrombosis After Drug-eluting Stent Implantation In Diabetic Patients.
Authors: Vassilis Voudris, Panagiotis Karyofillis, Sophia Thomopoulou, Sotitrios Patsilinakos, Athanasios Manginas, Constantinos Spargias, Gregory Pavlides, Dennis V. Cokkinos
Journal: Circulation (2007)

Background: Despite encouraging results with drug-eluting stents (DES) reported in diabetes mellitus (DM) patients (pts) with coronary artery disease, the long-term safety is unknown, because of late-onset stent thrombosis (LST). We investigated the incidence, risk factors and association of antiplatelet treatment (APLT) interruption for the development of LST in DM pts treated with DES during long-term clinical follow-up (FU). Methods: A total of 610 consecutive DM pts (male 80%, mean age 65 ± 9 years) had been treated with DES (sirolimus 80%, paclitaxel 10%, zotarolimus 2% combination 8%); 133 (22%) were on insulin treatment. Dual APLT treatment for 12 months received 93%, more than 12 months 72% and statin treatment 93% of pts. Clinical FU at least 12 months post-PCI (median 29 months, interquartile range 21 to 40) was obtained in 597/610 (98%) of pts. LST was defined as angiographic documentation of stent occlusion associated with an acute ischemic event, unexplained sudden cardiac death (D) or myocardial infarction (MI) not clearly attributable to another coronary lesion. Results: The incidence of LST was 2.18% (13 of 597 pts) and 6 additional pts (1%) developed stent thrombosis before 12 months (EST). All pts with LST (median time 19 months, interquartile range 14 to 24) had unexplained sudden cardiac D and 2/6 pts with EST non-fatal MI. Eleven out of 13 pts (85%) were on dual antiplatelet treatment at the time of LST. There was no difference in the incidence of LST between pts on oral antidiabetic medications and insulin treatment (2,1% vs. 2.3%, p:ns). In a multivariate model including clinical and angiographic factors, the only predictor for LST was ejection fraction &lt;40% (OR 0.10, 95% CI 0.03– 0.43, p&lt;0.05). Conclusion: LST in DM pts occurred in 2.18% after DES implantation; most of these pts were on dual APLT treatment. The only predictor of LST was depressed left ventricular function.
Abstract 13687: Global Rare Genic Copy Number Variants Contribute to Isolated Sporadic Tetralogy of Fallot
Authors: Rachel Soemedi, Ian Wilson, Rebecca Darlay, Jamie Bentham, Shoumo Bhattacharya, Catherine Cosgrove, David Brook, Javier Granados-Riveron, Kerry Setchfield, Frances Bu'Lock, Chris Thornborough, Koenraad Devriendt, Jeroen Breckpot, Michael Hofbeck, Mark Lathrop, Anita Rauch, David Winlaw, Heather Cordell, Mauro Santibanez-Koref, Judith Goodship, Bernard Keavney
Journal: Circulation (2011)

BACKGROUND: Copy number variants (CNV) occur in abundance and contribute to human phenotypic diversity. A recent population study suggests that CNV allele frequency is inversely correlated with CNV...
The significance of erythrocyte antigen site density
Authors: Leon W. Hoyer, Norma C. Trabold
Journal: Journal of Clinical Investigation (1970)

The importance of antigen site density has been studied by means of a model passive hemagglutination system using human red cells coupled with sulfanilic acid groups. Relative site numbers were estimated from the covalent linkage of sulfanilic acid-(35)S to red cell membrane protein and the effective antigen site number was determined with (125)I-labeled rabbit IgG antisulfanilic acid. Cells which had fewer than 20,000 antigen sites per cell were not agglutinated. As greater numbers of sulfanilic groups were coupled to the red cells, the agglutination titers increased to maximum values with red fanilic groups were coupled to the red cells, the agglutination titers of purified IgM antibody were 10-20 times greater than IgG antibody when preparations with the same protein concentration were compared, but this difference was not noted when IgG antibody was measured by antiglobulin reactions. These findings emphasize the need to consider differences in antigen site density when comparing blood group systems. They are consistent with the hypothesis that those blood group antigens which have a very low site number will not be detected by IgG antibodies in saline hemagglutination determinations.
Abstract 20004: Aging-Associated Changes in Human Atrial Bioenergetics and Metabolomic Profile Detected by GC/MS and Stable Isotope 18O-assisted Mass Spectrometry
Authors: Viqar Maria, Anu Gupta, Emirhan Nemutlu, Song Zhang, Sulaiman Sultan, Mahek Mirza, Petras Dzeja, Arshad Jahangir
Journal: Circulation (2010)

Introduction:  Aging-associated alteration in atrial bioenergetics may increase predisposition to electrical and mechanical dysfunction, but has not been fully characterized in human myocardium.   Hypothesis:  Simultaneous determination of metabolite level and turnover rates can reveal dynamic metabolic rearrangements in aging human atria.   Methods:  Right atrial appendage tissue from 7 aged (mean age 70.1±6.7 yrs) and 7 adult (53.4±4.7 yrs) patients, free of atrial pathology undergoing coronary artery bypass surgery were subjected to metabolite 18O-labeling. Tissue extracts were analyzed using HPLC, GC/MS and stable isotope 18O-assisted mass spectrometry (18O-assisted GC/MS).   Results:  PLS DA (Partial Least Square Discriminant Analysis) score plot exhibited distinct clustering of metabolites and 18O-labeling rates between the two age groups (Figure). Selected metabolites of fatty acid, Krebs cycle, glycolysis and nucleotide metabolism, and turnover rates of inorganic phosphate (Pi) (ATP turnover), glucose-6-phosphate (G-6-P) (glycolysis), glucose-1-phosphate (G-1-P) (glycogenolysis) and glycerol-3-phosphate (G-3-P) (mitochondrial substrate shuttle) were differentially altered with aging (Figure). G-6-P and G-3-P turnover rates were higher, while Pi (ATP) turnover and nucleotide (adenosine, AMP) levels were lower in aged human atria.   Conclusions:  Thus, metabolomic profiling and 18O-assisted GC/MS analysis of metabolite turnover rates through different metabolic pathways revealed aging-associated dynamic rearrangements in atrial energetic system with potential implications in detecting the effect of aging and aging-associated diseases on atrial structure and function.
Abstract 11077: Differential Prognostic Effect of Revascularization According to Comorbidities in High-Risk Non ST-Segment Elevation Acute Coronary Syndromes
Authors: Patricia Palau, Julio Nunez, Juan Sanchis, Vicent Bodi, Gema Minana, Clara Bonanad, Silvia Ventura, Angel Llacer
Journal: Circulation (2011)

Background: Data on the effect of revascularization on outcome in patients with high-risk non ST-segment elevation acute coronary syndrome (NSTEACS) and significant comorbidities are scarce. Recent...
Antibiotics for acute sinusitis in general practice
Authors: G G Browning, J. P A Ioannidis, S. D de Ferranti, M. Barza, J. Lau
Journal: BMJ (1999)

Is there a rationale for rationing chronic dialysis? Two points need clarificationEditor-I agree with Chandna et al that late referral is an important factor in the survival of patients receiving dialysis. 1I am unaware, however, of the source of their information that an NHS consensus statement recommends that nephrology referrals be made at a serum creatinine concentration > 135 mol/l in women and > 180 mol/l in men.The workload generated by this practice would be so enormous that British renal units under present conditions would be unable to cope.I am also concerned that of the authors' 292 patients receiving dialysis, 26 (admittedly high risk) patients spent 44% of their lives in hospital.The costs of inpatient treatment for these high risk patients would be substantially higher than the average cost of £250 a day that the authors quote.
Abstract 16183: Deleterious Impact of Poor Adherence to Statin Therapy on Long-term Outcomes after Acute Myocardial Infarction: A Nationwide French Survey of Administrative Data.
Authors: Anke Neumann, Philippe Tuppin, Nicolas Danchin, Alain Weill, Philippe Ricordeau, Christine De Peretti, Hubert Allemand
Journal: Circulation (2010)

Aim: To assess the long-term risk of death or recurrent ACS according to adherence to statin therapy in patients discharged on statins after AMI. Methods: Thirty-month observational follow-up of patients admitted for AMI in France in the first 6 months 2006. Data from three administratives sources were linked for all patients covered by the general health insurance scheme (70% of the French population): the national hospital discharge database, the outpatients medications reimbursement database, and the national mortality database. All patients who filled an initial prescription of statins immediately following hospital discharge and remained in the study after 6-month follow-up (10,501 patients) were included. Adherence was defined as >80% of days of follow-up covered by a filled prescription for statins. ACS-free survival was compared between adherent and non adherent patients, adjusting for sociodemographic and medical factors, using Cox multivariate analysis. Results: Of the 10,501 patients on statins...
Loss of caspase-8 expression does not correlate with MYCN amplification, aggressive disease or prognosis in neuroblastoma: A putative tumor suppressor revised?
Authors: Simone Fulda, Christopher Poremba, Bernd Berwanger, Sabine Häcker, Martin Eilers, Holger Christiansen, Barbara Hero, Klaus-Michael Debatin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

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Inactivation of caspase-8 because of aberrant gene methylation has been associated with amplification of the MYCN oncogene and aggressive disease in neuroblastoma suggesting that caspase-8 may function as tumor suppressor. However, the prognostic impact of caspase-8 in neuroblastoma has remained obscure. Therefore, we investigated caspase-8 expression and its correlation with established prognostic markers and survival outcome in a large cohort of neuroblastoma patients. Here, we report that loss of caspase-8 protein expression occurs in the majority (75%) of neuroblastoma and is not restricted to advanced disease stages. Surprisingly, no correlation was observed between caspase-8 expression and MYCN amplification. Similarly, ectopic expression of MYCN or antisense-mediated downregulation of MYCN had no effect on caspase-8 expression in neuroblastoma cell lines. Also, caspase-8 expression did not correlate with other parameters of high-risk disease, e.g. 1p36 aberrations, disease stage, age at diagnosis or tumor histology. Most importantly, loss of caspase-8 protein had no impact on event-free or overall survival in the overall study population or in distinct subgroups of patients. By revealing no correlation between caspase-8 expression and MYCN amplification or other established parameters of aggressive disease, our findings in a large cohort of neuroblastoma patients challenge the previous concept of MYCN-driven inactivation of caspase-8 in advanced neuroblastoma. Thus, our study provides novel insight into the biology of this tumor, which has important clinical implications.
Treatment options may be limited by resources
Authors: Pelton Christopher I, 付晓霞
Journal: BMJ (2005)

在过去的15年中，我就职于一所大型医院，这所医院位于一个新兴城镇的市区。在这期间，我看到了越来越多不开心的孩子以及所谓抑郁的孩子。我也曾经做过学校的医生。这些年来公众的注意力和医疗资源从精神病学和为儿童服务转移到了老年慢性病上。因此我经常面临对孩子们是处方抗抑郁药还是什么都不做的两难境地。现在我很高兴看到有了关于儿童抑郁的争论，并对作者Timimi所持论点(见本刊2005年第2期121页)表示赞同，但是，“治疗”那些不开心的儿童是社会赋予我的不可推卸的责任。