tbuckley/cabot-search huggingface dataset:
Correlative Aspects of Introjective and Projective Mechanisms
Authors: W. W. MEISSNER
Journal: American Journal of Psychiatry (1974)

The author discusses the correlative nature of projection and introjection, their early roles in development and differentiation, and their later defensive uses. He describes how, in paranoid states, the interplay between projecting and introjecting leads to conflicted ambivalence between preserving and annihilating significant objects.
Heritability of Chronic Obstructive Pulmonary Disease and Related Phenotypes in Smokers
Authors: Jin J. Zhou, Michael H. Cho, Peter J. Castaldi, Craig P. Hersh, Edwin K. Silverman, Nan M. Laird
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Previous studies of chronic obstructive pulmonary disease (COPD) have suggested that genetic factors play an important role in the development of disease. However, single-nucleotide polymorphisms that are associated with COPD in genome-wide association studies have been shown to account for only a small percentage of the genetic variance in phenotypes of COPD, such as spirometry and imaging variables. These phenotypes are highly predictive of disease, and family studies have shown that spirometric phenotypes are heritable.To assess the heritability and coheritability of four major COPD-related phenotypes (measurements of FEV1, FEV1/FVC, percent emphysema, and percent gas trapping), and COPD affection status in smokers of non-Hispanic white and African American descent using a population design.Single-nucleotide polymorphisms from genome-wide association studies chips were used to calculate the relatedness of pairs of individuals and a mixed model was adopted to estimate genetic variance and covariance.In the non-Hispanic whites, estimated heritabilities of FEV1 and FEV1/FVC were both about 37%, consistent with estimates in the literature from family-based studies. For chest computed tomography scan phenotypes, estimated heritabilities were both close to 25%. Heritability of COPD affection status was estimated as 37.7% in both populations.This study suggests that a large portion of the genetic risk of COPD is yet to be discovered and gives rationale for additional genetic studies of COPD. The estimates of coheritability (genetic covariance) for pairs of the phenotypes suggest considerable overlap of causal genetic loci.
Podocin and Nephrotic Syndrome
Authors: Patrick Niaudet
Journal: Journal of the American Society of Nephrology (2004)

Idiopathic nephrotic syndrome (INS) is the most frequent glomerular disease in childhood. Most of the children respond to corticosteroid therapy whereas 10% of them fail to respond to this treatment. They are at risk of extrarenal complications of the nephrotic syndrome and may develop end-stage
The Role of p27 Kip1 in Dasatinib-Enhanced Paclitaxel Cytotoxicity in Human Ovarian Cancer Cells
Authors: Xiao-Feng Le, Weiqun Mao, Guangan He, Francois-Xavier Claret, Weiya Xia, Ahmed Ashour Ahmed, Mien-Chie Hung, Zahid H. Siddik, Robert C. Bast
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundLess than 50% of ovarian cancers respond to paclitaxel. Effective strategies are needed to enhance paclitaxel sensitivity.
Inhibition of Heme Oxygenase-1 Increases Responsiveness of Pancreatic Cancer Cells to Anticancer Treatment
Authors: Pascal O. Berberat, Zilvinas Dambrauskas, Antanas Gulbinas, Thomas Giese, Nathalia Giese, Beat Künzli, Frank Autschbach, Stefen Meuer, Markus W. Büchler, Helmut Friess
Journal: Clinical Cancer Research (2005)

Abstract Heme oxygenase-1 (HO-1) is believed to represent a key enzyme for the protection of cells against “stress.” Its overexpression in different types of human cancers supports the notion that HO-1 provides a growth advantage and contributes to cellular resistance against chemotherapy and radiotherapy. Given the poor survival rates of patients with pancreatic cancer due to its aggressive growth behavior and its exceptional resistance to all known forms of anticancer treatment, we have investigated the expression of HO-1 in human pancreatic cancer cells growth behavior and prognosis. Expression of HO-1 was analyzed in human pancreatic cancer samples in comparison with normal pancreas by quantitative PCR, Western blot, and confocal microscopy. The influence of radiotherapy and chemotherapy on HO-1 expression in pancreatic cancer cell lines was evaluated. Furthermore, HO-1 expression was specifically suppressed by small interfering RNA transfection and subsequently the alterations of growth behavior and resistance to anticancer treatment were tested. Human pancreatic cancer showed a 6-fold and 3.5-fold HO-1 up-regulation in comparison to normal pancreas based on mRNA and protein level, respectively (P &amp;lt; 0.05). Cancer tissues revealed marked HO-1 immunoreactivity in tumor cells and in tumor associated immunocytes. Treatment of the pancreatic cancer cell lines with gemcitabine or radiation strongly induced HO-1 expression. Targeted knockdown of HO-1 expression led to pronounced growth inhibition of the pancreatic cancer cells and made tumor cells significantly more sensitive to radiotherapy and chemotherapy. Therefore, specific inhibition of HO-1 expression may be a new option in pancreatic cancer therapy and may be used as sensitizer to chemotherapy and radiotherapy.
Cutaneous immunosurveillance by self-renewing dermal γδ T cells
Authors: Nital Sumaria, Ben Roediger, Lai Guan Ng, Jim Qin, Rachel Pinto, Lois L. Cavanagh, Elena Shklovskaya, Barbara Fazekas de St. Groth, James A. Triccas, Wolfgang Weninger
Journal: The Journal of Experimental Medicine (2011)

The presence of γδ T cell receptor (TCR)–expressing cells in the epidermis of mice, termed dendritic epidermal T cells (DETCs), is well established. Because of their strict epidermal localization, it is likely that DETCs primarily respond to epithelial stress, such as infections or the presence of transformed cells, whereas they may not participate directly in dermal immune responses. In this study, we describe a prominent population of resident dermal γδ T cells, which differ from DETCs in TCR usage, phenotype, and migratory behavior. Dermal γδ T cells are radioresistant, cycle in situ, and are partially depend on interleukin (IL)-7, but not IL-15, for their development and survival. During mycobacterial infection, dermal γδ T cells are the predominant dermal cells that produce IL-17. Absence of dermal γδ T cells is associated with decreased expansion in skin draining lymph nodes of CD4+ T cells specific for an immunodominant Mycobacterium tuberculosis epitope. Decreased CD4+ T cell expansion is related to a reduction in neutrophil recruitment to the skin and decreased BCG shuttling to draining lymph nodes. Thus, dermal γδ T cells are an important part of the resident cutaneous immunosurveillance program. Our data demonstrate functional specialization of T cells in distinct microcompartments of the skin.
Primary Angioplasty Versus Fibrinolysis in Acute Myocardial Infarction
Authors: Peter H. Nielsen, Michael Maeng, Martin Busk, Leif S. Mortensen, Steen D. Kristensen, Torsten T. Nielsen, Henning R. Andersen
Journal: Circulation (2010)

Background— The Danish Acute Myocardial Infarction 2 (DANAMI-2) study found that primary angioplasty (primary percutaneous coronary intervention [pPCI]) compared with fibrinolysis reduced 30-day adverse events in patients with ST-segment elevation myocardial infarction. The present study investigated whether the benefit of pPCI was maintained at a long-term follow-up. Methods and Results— We randomly assigned 1572 patients with ST-segment elevation myocardial infarction—1129 patients at referral hospitals and 443 patients at invasive hospitals—to pPCI or fibrinolysis. Median time from randomization to arrival in the catheterization laboratory for patients admitted to referral hospitals was 67 minutes, with 96% of patients arriving in the catheterization laboratory within 120 minutes. The primary study end point was a composite of death or reinfarction. Median follow-up time was 7.8 years. For the primary end point, 8-year cumulative incidence (1-Kaplan–Meier) was 34.8% in the pPCI group and 41.3% in the fibrinolysis group (hazard ratio, 0.78; 95% confidence interval, 0.66 to 0.92). Reinfarction rates were reduced in the pPCI group (11.7% versus 18.5%; hazard ratio, 0.60; 95% confidence interval, 0.46 to 0.77). Among patients randomized at referral hospitals, pPCI reduced reinfarction (13% versus 18.5%; hazard ratio, 0.66; 95% confidence interval, 0.49 to 0.89) and mortality (26.7% versus 33.3%; hazard ratio, 0.78; 95% confidence interval, 0.63 to 0.97). Conclusions— The benefit of pPCI over fibrinolysis was maintained at a long-term follow-up. pPCI reduced the risk of reinfarction in the overall cohort and reduced reinfarction and mortality among patients randomized at referral hospitals. This result reinforces that pPCI should be offered to ST-segment elevation myocardial infarction patients when interhospital transport to an invasive hospital can be completed within 120 minutes.
Neuropeptide Y may mediate psychological stress and enhance TH2 inflammatory response in asthma
Authors: Yanxia Lu, Roger Ho, Tow Keang Lim, Win Sen Kuan, Daniel Yam Thiam Goh, Malcolm Mahadevan, Tiong Beng Sim, Hugo P.S. Van Bever, Anis Larbi, Tze Pin Ng
Journal: Journal of Allergy and Clinical Immunology (2014)
Immunohistochemical localization of endothelial cell-derived lipase in atherosclerotic human coronary arteries
Authors: H Azumi
Journal: Cardiovascular Research (2003)

Objective: A novel lipoprotein lipase (LPL)-like gene, endothelial cell-derived lipase (EDL), was recently cloned from vascular endothelial cells. The presence of LPL in the vascular wall has been implicated in the progression of atherosclerosis through the bridging function between lipoprotein particles and matrix proteoglycans to enhance lipoprotein uptake into the vascular wall. The aim of this study was to investigate the local expression of EDL in human coronary arteries. Methods and Results: Human coronary arterial specimens from 10 autopsied cases were examined by immunohistochemistry with polyclonal antibodies against specific synthetic EDL peptides. Immunohistochemical analysis revealed that EDL was expressed in endothelial cells and medial smooth muscle cells in non-atherosclerotic coronary arteries. In addition, EDL was expressed in infiltrating cells within atheromatous plaques as well as endothelial and smooth muscle cells. Double labeling immunofluorescence confirmed EDL positive-cells were endothelial cells, smooth muscle cells and macrophages. EDL immunoreactivity was also detected in neovasculature within atheromatous plaques in atherosclerotic coronary arteries. Conclusions: These results suggest that EDL may have unique functional roles in the pathogenesis of coronary artery diseases such as atherosclerosis as well as in lipid metabolism in the vessel wall.
A Novel Host Defense System of Airways Is Defective in Cystic Fibrosis
Authors: Patryk Moskwa, Daniel Lorentzen, Katherine J. D. A. Excoffon, Joseph Zabner, Paul B. McCray, William M. Nauseef, Corinne Dupuy, Botond Bánfi
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

The respiratory tract is constantly exposed to airborne microorganisms. Nevertheless, normal airways remain sterile without recruiting phagocytes. This innate immune activity has been attributed to mucociliary clearance and antimicrobial polypeptides of airway surface liquid. Defective airway immunity characterizes cystic fibrosis (CF), a disease caused by mutations in the CF transmembrane conductance regulator, a chloride channel. The pathophysiology of defective immunity in CF remains to be elucidated.We investigated the ability of non-CF and CF airway epithelia to kill bacteria through the generation of reactive oxygen species (ROS).ROS production and ROS-mediated bactericidal activity were determined on the apical surfaces of human and rat airway epithelia and on cow tracheal explants.Dual oxidase enzyme of airway epithelial cells generated sufficient H(2)O(2) to support production of bactericidal hypothiocyanite (OSCN(-)) in the presence of airway surface liquid components lactoperoxidase and thiocyanate (SCN(-)). This OSCN(-) formation eliminated Staphylococcus aureus and Pseudomonas aeruginosa on airway mucosal surfaces, whereas it was nontoxic to the host. In contrast to normal epithelia, CF epithelia failed to secrete SCN(-), thereby rendering the oxidative antimicrobial system inactive.These data indicate a novel innate defense mechanism of airways that kills bacteria via ROS and suggest a new cellular and molecular basis for defective airway immunity in CF.
Activation of the NRF2 pathway and its impact on the prognosis of anaplastic glioma patients
Authors: Masayuki Kanamori, Tsuyoshi Higa, Yukihiko Sonoda, Shohei Murakami, Mina Dodo, Hiroshi Kitamura, Keiko Taguchi, Tatsuhiro Shibata, Mika Watanabe, Hiroyoshi Suzuki, Ichiyo Shibahara, Ryuta Saito, Yoji Yamashita, Toshihiro Kumabe, Masayuki Yamamoto, Hozumi Motohashi, Teiji Tominaga
Journal: Neuro-Oncology (2014)

Nuclear factor erythroid 2–related factor 2 (NRF2) plays pivotal roles in cytoprotection. We aimed at clarifying the contribution of the NRF2 pathway to malignant glioma pathology. NRF2 target gene expression and its association with prognosis were examined in 95 anaplastic gliomas with or without isocitrate dehydrogenase (IDH) 1/2 gene mutations and 52 glioblastomas. To explore mechanisms for the altered activity of the NRF2 pathway, we examined somatic mutations and expressions of the NRF2 gene and those encoding NRF2 regulators, Kelch-like ECH-associated protein 1 (KEAP1) and p62/SQSTSM. To clarify the functional interaction between IDH1 mutations and the NRF2 pathway, we introduced a mutant IDH1 to T98 glioblastoma-derived cells and examined the NRF2 activity in these cells. NRF2 target genes were elevated in 13.7% and 32.7% of anaplastic gliomas and glioblastomas, respectively. Upregulation of NRF2 target genes correlated with poor prognosis in anaplastic gliomas but not in glioblastomas. Neither somatic mutations of NRF2/KEAP1 nor dysregulated expression of KEAP1/p62 explained the increased expression of NRF2 target genes. In most cases of anaplastic glioma with mutated IDH1/2, NRF2 and its target genes were downregulated. This was reproducible in IDH1 R132H–expressing T98 cells. In minor cases of IDH1/2-mutant anaplastic gliomas with increased expression of NRF2 target genes, the clinical outcomes were significantly poor. The NRF2 activity is increased in a significant proportion of malignant gliomas in general but decreased in the majority of IDH1/2-mutant anaplastic gliomas. It is plausible that the NRF2 pathway plays an important role in tumor progression of anaplastic gliomas with IDH1/2 mutations.
Systematic review of long term effects of advice to reduce dietary salt in adults
Authors: L. Hooper
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the long term effects of advice to restrict dietary sodium in adults with and without hypertension. <b>Design:</b> Systematic review and meta-analysis of randomised controlled trials. <b>Data sources:</b> Cochrane library, Medline, Embase, and bibliographies. <b>Study selection:</b> Unconfounded randomised trials that aimed to reduce sodium intake in healthy adults over at least 6 months. Inclusion decisions, validity and data extraction were duplicated. Random effects meta-analysis, subgrouping, sensitivity analysis, and meta-regression were performed. <b>Outcomes:</b> Mortality, cardiovascular events, blood pressure, urinary sodium excretion, quality of life, and use of antihypertensive drugs. <b>Results:</b> Three trials in normotensive people (n=2326), five trials in those with untreated hypertension (n=387), and three trials in people being treated for hypertension (n=801) were included, with follow up from six months to seven years. The large high quality (and therefore most informative) studies used intensive behavioural interventions. Deaths and cardiovascular events were inconsistently defined and reported. There were 17 deaths, equally distributed between intervention and control groups. Systolic and diastolic blood pressures were reduced (systolic by 1.1 mm Hg, 95% confidence interval 1.8 to 0.4 mm Hg; diastolic by 0.6 mm Hg, 1.5 to 0.3 mm Hg) at 13 to 60 months, as was urinary 24 hour sodium excretion (by 35.5 mmol/24 hours, 47.2 to 23.9). Degree of reduction in sodium intake and change in blood pressure were not related. <b>Conclusions:</b> Intensive interventions, unsuited to primary care or population prevention programmes, provide only small reductions in blood pressure and sodium excretion, and effects on deaths and cardiovascular events are unclear. Advice to reduce sodium intake may help people on antihypertensive drugs to stop their medication while maintaining good blood pressure control.
Intravital 2-photon imaging of leukocyte trafficking in beating heart
Authors: Wenjun Li, Ruben G. Nava, Alejandro C. Bribriesco, Bernd H. Zinselmeyer, Jessica H. Spahn, Andrew E. Gelman, Alexander S. Krupnick, Mark J. Miller, Daniel Kreisel
Journal: Journal of Clinical Investigation (2012)

Two-photon intravital microscopy has substantially broadened our understanding of tissue- and organ-specific differences in the regulation of inflammatory responses. However, little is known about the dynamic regulation of leukocyte recruitment into inflamed heart tissue, largely due to technical difficulties inherent in imaging moving tissue. Here, we report a method for imaging beating murine hearts using intravital 2-photon microscopy. Using this method, we visualized neutrophil trafficking at baseline and during inflammation. Ischemia reperfusion injury induced by transplantation or transient coronary artery ligation led to recruitment of neutrophils to the heart, their extravasation from coronary veins, and infiltration of the myocardium where they formed large clusters. Grafting hearts containing mutant ICAM-1, a ligand important for neutrophil recruitment, reduced the crawling velocities of neutrophils within vessels, and markedly inhibited their extravasation. Similar impairment was seen with the inhibition of Mac-1, a receptor for ICAM-1. Blockade of LFA-1, another ICAM-1 receptor, prevented neutrophil adherence to endothelium and extravasation in heart grafts. As inflammatory responses in the heart are of great relevance to public health, this imaging approach holds promise for studying cardiac-specific mechanisms of leukocyte recruitment and identifying novel therapeutic targets for treating heart disease.
Initial steps of insulin signaling and glucose transport are defective in the type 2 diabetic rat heart
Authors: M Desrois
Journal: Cardiovascular Research (2003)

Objective: Whole body insulin resistance and diabetes are risk factors for cardiovascular diseases, yet little is known about insulin resistance in the diabetic heart. The aim of this work was to define the insulin response in hearts of the Goto–Kakizaki (GK) rat, a polygenic model of spontaneous type 2 diabetes. Methods: We measured d[2-3H]glucose uptake before and after insulin stimulation, plus initial steps of the insulin signaling pathway after insulin infusion via the caudal vena cava in hearts from the male Wistar and spontaneously diabetic GK rats. Results: Despite normal basal d[2-3H]glucose uptake, insulin-stimulated glucose uptake was 50% (p<0.03) lower in GK rat hearts compared with their Wistar controls. Total GLUT4 protein was depleted by 28% (p<0.01) in GK rat hearts. We found 31% (p<0.0001) and 38% (p<0.001) decreased protein levels of insulin receptor β (IRβ)-subunit and insulin receptor substrate-1 (IRS-1), respectively, in GK rat hearts with 37% (p<0.02) and 45% (p<0.01) lower insulin-stimulated tyrosine phosphorylation of these proteins. Owing to the decreased IRS-1 protein levels, GK rat hearts had a 41% (p<0.0001) decrease in insulin-stimulated IRS-1 protein association with the p85 subunit of phosphatidylinositol 3-kinase, despite normal phosphatidylinositol 3-kinase protein expression. Insulin-stimulated serine phosphorylation of protein kinase B was the same in all hearts, as was protein kinase B expression. Conclusion: We conclude that decreased insulin receptor β, IRS-1 and GLUT4 proteins are associated with insulin resistance in type 2 diabetic rat hearts.
Spontaneous pneumothorax: comparison of simple drainage, talc pleurodesis, and tetracycline pleurodesis.
Authors: M Almind, P Lange, K Viskum
Journal: Thorax (1989)

From 1978 to 1985 96 patients with their first spontaneous pneumothorax were randomised into three groups, receiving either treatment with simple drainage (34 patients), drainage with tetracycline pleurodesis (33 patients), or drainage with talc pleurodesis (29 patients). There were 58 men and 38 women, aged 18-88 years. There was no significant difference between the three groups in the mean time in hospital or the period for which the drains were retained. The incidence of infection, persistent pneumothorax, and relapse while in hospital was also similar for the three groups. At follow-up in 1987-89 patients could be accounted for, with an average follow-up period of 4.6 years. The incidence of recurrence was 36% in the simple drainage group, 13% in the tetracycline pleurodesis group, and 8% in the talc pleurodesis group. The difference between the talc and simple drainage groups was significant. None of the methods caused severe short or long term side effects or changes in the follow-up chest radiograph. Thoracoscopy, performed on admission in 85 patients, showed normal appearances in 73 patients and small cysts in 12. The thoracoscopic findings were of no value in predicting recurrence. Talc pleurodesis resulted in a significantly lower recurrence rate than simple drainage, tetracycline pleurodesis having intermediate efficacy.
Synergistic Proapoptotic Activity of Recombinant TRAIL Plus the Akt Inhibitor Perifosine in Acute Myelogenous Leukemia Cells
Authors: Pier Luigi Tazzari, Giovanna Tabellini, Francesca Ricci, Veronica Papa, Roberta Bortul, Francesca Chiarini, Camilla Evangelisti, Giovanni Martinelli, Andrea Bontadini, Lucio Cocco, James A. McCubrey, Alberto M. Martelli
Journal: Cancer Research (2008)

Abstract To potentiate the response of acute myelogenous leukemia (AML) cells to tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) cytotoxicity, we have examined the efficacy of a combination with perifosine, a novel phosphatidylinositol-3-kinase (PI3K)/Akt signaling inhibitor. The rationale for using such a combination is that perifosine was recently described to increase TRAIL-R2 receptor expression and decrease the cellular FLICE-inhibitory protein (cFLIP) in human lung cancer cell lines. Perifosine and TRAIL both induced cell death by apoptosis in the THP-1 AML cell line, which is characterized by constitutive PI3K/Akt activation, but lacks functional p53. Perifosine, at concentrations below IC50, dephosphorylated Akt and increased TRAIL-R2 levels, as shown by Western blot, reverse transcription-PCR, and flow cytometric analysis. Perifosine also decreased the long isoform of cFLIP (cFLIP-L) and the X-linked inhibitor of apoptosis protein (XIAP) expression. Perifosine and TRAIL synergized to activate caspase-8 and induce apoptosis, which was blocked by a caspase-8–selective inhibitor. Up-regulation of TRAIL-R2 expression was dependent on a protein kinase Cα/c-Jun-NH2-kinase 2/c-Jun signaling pathway activated by perifosine through reactive oxygen species production. Perifosine also synergized with TRAIL in primary AML cells displaying constitutive activation of the Akt pathway by inducing apoptosis, Akt dephosphorylation, TRAIL-R2 up-regulation, cFLIP-L and XIAP down-regulation, and c-Jun phosphorylation. The combined treatment negatively affected the clonogenic activity of CD34+ cells from patients with AML. In contrast, CD34+ cells from healthy donors were resistant to perifosine and TRAIL treatment. Our findings suggest that the combination of perifosine and TRAIL might offer a novel therapeutic strategy for AML. [Cancer Res 2008;68(22):9394–403]