tbuckley/cabot-search huggingface dataset:
NiO and Co3O4 nanoparticles induce lung DTH-like responses and alveolar lipoproteinosis
Authors: W.-S. Cho, R. Duffin, M. Bradley, I. L. Megson, W. MacNee, S. E. M. Howie, K. Donaldson
Journal: European Respiratory Journal (2011)

Lung exposure to metal oxide nanoparticles (NPs) comprising soluble metal haptens may produce T-helper cell type 1 (Th1)- and Th17-associated delayed-type hypersensitivity (DTH) responses and pulmonary alveolar proteinosis (PAP). In order to study this, haptenic metal oxide NPs (NiO, Co 3 O 4 , Cr 2 O 3 and CuO) were instilled into the lungs of female Wistar rats, and the immunoinflammatory responses were assessed at 24 h and 4 weeks post-instillation. Primary culture of alveolar macrophages from Wistar rats was used to evaluate the effect of the NPs on the ability to clear surfactant. NiO NPs induced chronic interstitial inflammation and pro-inflammatory Th1 and Th17 immune responses characterised by increases in the cytokines monocyte chemotactic protein (MCP)-1/CCL2, interleukin (IL)-12 p40, interferon-γ and IL-17A, whilst similar pathological responses induced by Co 3 O 4 NPs were associated with increases in MCP-1/CCL2 and IL-12 p40. However, neither Cr 2 O 3 nor CuO NPs elicited immunoinflammatory reactions. PAP was induced by both NiO and Co 3 O 4 NPs during the chronic phase. PAP was associated with over-production of surfactant by proliferation of type II cells and impaired clearance of surfactant by macrophages. These findings have implications for the risk management of occupational NP exposure and provide evidence that haptenic metal oxide NPs can induce chronic progressive lung immune responses via a DTH-like mechanism.
Malignant melanoma: aetiological importance of individual pigmentation and sun exposure
Authors: H. BEITNER, S.E. NORELL, U. RINGBORG, G. WENNERSTEN, B. MATTSON
Journal: British Journal of Dermatology (1990)

A case-control study of cutaneous malignant melanoma (CMM) was based on 523 incident cases and 505 age- and sex-matched controls selected from the general population. The purpose was to investigate the relative risk of developing CMM associated with different sun habits and indicators of pigmentation, such as skin type, eye colour and hair colour. Compared to people with black hair, blonde subjects had a relative risk of 74.4 (95% confidence interval, 45.8-120.8). Associations with skin type and eye colour were considerably weaker. Relative risks of about 1.5-2.5 were found for certain sun habits. The results suggest that in a population of Caucasian origin with a predominantly fair complexion, pigmentary status characterized by hair colour is a far more important aetiological factor than sun habits.
A Review of the Mental Health Issues of Diabetes Conference
Authors: Lee Ducat, Arthur Rubenstein, Louis H. Philipson, Barbara J. Anderson
Journal: Diabetes Care (2015)

Individuals with type 1 diabetes are at increased risk for depression, anxiety disorder, and eating disorder diagnoses. People with type 1 diabetes are also at risk for subclinical levels of diabetes distress and anxiety. These mental/behavioral health comorbidities of diabetes are associated with poor adherence to treatment and poor glycemic control, thus increasing the risk for serious short- and long-term physical complications, which can result in blindness, amputations, stroke, cognitive decline, decreased quality of life, as well as premature death. When mental health comorbidities of diabetes are not diagnosed and treated, the financial cost to society and health care systems is catastrophic, and the human suffering that results is profound. This review summarizes state-of-the-art presentations and working group scholarly reports from the Mental Health Issues of Diabetes Conference(7–8 October 2013, Philadelphia, PA), which included stakeholders from the National Institutes of Health, people living with type 1 diabetes and their families, diabetes consumer advocacy groups, the insurance industry, as well as psychologists, psychiatrists, endocrinologists, and nurse practitioners who are all nationally and internationally recognized experts in type 1 diabetes research and care. At this landmark conference current evidence for the incidence and the consequences of mental health problems in type 1 diabetes was presented, supporting the integration of mental health screening and mental health care into routine diabetes medical care. Future research directions were recommended to establish the efficacy and cost-effectiveness of paradigms of diabetes care in which physical and mental health care are both priorities.
The Nuclear Factor κB Subunits RelA/p65 and c-Rel Potentiate but Are Not Required for Ras-Induced Cellular Transformation
Authors: Julie L. Hanson, Noel A. Hawke, David Kashatus, Albert S. Baldwin
Journal: Cancer Research (2004)

Extensive data indicate that oncoproteins, such as oncogenic H-Ras, initiate signal transduction cascades that ultimately lead to the activation of specific transcription factors. We and others have previously demonstrated that Ras activates the inherent transcriptional activation function of the transcription factor nuclear factor kappaB (NF-kappaB). Supportive of the importance of NF-kappaB in transformation, Ras-induced cellular transformation can be suppressed by expression of IkappaBalpha, an inhibitor of NF-kappaB, or by dominant-negative forms of the upstream activator IkappaB kinase (IKK). However, conclusive evidence for a requirement for NF-kappaB subunits in oncogenic transformation has not been reported. Furthermore, there is little understanding of the gene targets controlled by NF-kappaB that might support oncogenic conversion. The data presented here demonstrate that, although both p65 and c-Rel enhance the frequency of Ras-induced cellular transformation, these NF-kappaB subunits are not essential for Ras to transform spontaneously immortalized murine fibroblasts. Microarray analysis identified a set of genes induced by Ras that is dependent on NF-kappaB for their expression and that likely play contributory roles in promoting Ras-induced oncogenic transformation.
Study on the Evolution of the Grande Retrotransposon in the Zea Genus
Authors: J. Garcia-Martinez
Journal: Molecular Biology and Evolution (2003)

The study of Grande retrotransposon (RTN) variation reported here comprises the intrinsic element variability and the changes that element insertion provokes in the Zea genome, including its abundance among species. Sequence analysis of a defined long-terminal repeat (LTR) region from Grande RTN revealed a high level of sequence divergence since no identical sequences were found among the 65 clones examined that belong to different Zea species or maize inbred lines. Average diversity values within accessions ranged from 0.17 to 0.37 substitutions per nucleotide. Phylogenetic analysis revealed a lack of concordance between the phylogenetic tree obtained from LTR sequences and the conventional taxonomic tree, suggesting that different subfamilies of Grande elements existed before Zea speciation. When sequence-specific amplification polymorphism (SSAP) marker data, which combines genomic and RTN variation, are used, the derived trees reflect the established species phylogeny and allow, as well, differentiating among some maize lines. Finally, the evaluation of Grande abundance, using different element probes in all the Zea species but Z. luxurians, revealed around 5,700 copies per haploid genome in all the diploid species examined, indicating a similar expansion process of Grande in all the Zea genomes. This number of copies represents in all cases around a 3% of the genome, which implies that Grande RTN is an important component of the maize genome. The copy number ratio LTR/gag is around 2 in all the species analyzed, indicating that overwhelming majority of elements have internal region. Thus, mechanisms such as homologous recombination between LTRs of a single RTN, which would remove the internal region and one LTR, leaving behind a single recombinant LTR, seems not to be active in maize for Grande RTN.
Searching for the Second-Best Coronary Artery Bypass Graft
Authors: Timothy J. Gardner
Journal: Circulation (2007)

irtually all cardiac surgeons and their referring cardiologists know that the most effective and reliable coronary artery bypass conduit is the pedicled internal thoracic (mammary) artery (LITA) when placed to the left anterior descending artery coronary artery (LAD).This first choice of bypass graft conduits is based on convincing evidence of improved survival in patients with critical LAD disease in whom an LITA graft has been placed. 1,2The importance of an LITA graft when bypassing the LAD is so well accepted that it is now used as a quality indicator in the assessment of the performance of cardiac surgery programs in coronary artery bypass graft surgery (CABG).
Lung sarcoidosis in children: update on disease expression and management
Authors: Nadia Nathan, Pierre Marcelo, Véronique Houdouin, Ralph Epaud, Jacques de Blic, Dominique Valeyre, Anne Houzel, Pierre-François Busson, Harriet Corvol, Antoine Deschildre, Annick Clement
Journal: Thorax (2015)

<h3>Background</h3> Sarcoidosis is a rare lung disease in children. The aim of the present study was to provide update information on disease presentation and progression, patient management and prognosis factors in a cohort of children with lung sarcoidosis. <h3>Methods</h3> With the network of the French Reference Centre for Rare Lung Diseases (RespiRare), we collected information on a large cohort of paediatric thoracic sarcoidosis to provide information on disease presentation, management and outcome. <h3>Results</h3> Forty-one patients were included with a median age at diagnosis of 11.8 years (1.1–15.8), mostly from Afro-Caribbean and Sub-Saharan origin. At diagnosis, 85% presented with a multi-organic disease, and no major differences were found regarding disease severity between the patients diagnosed before or after 10 years old. Corticosteroids were the most used treatment, with more intravenous pulses in the youngest patients. The 18-month outcome showed that patients diagnosed before 10 years old were more likely to recover (50% vs 29%), and presented fewer relapses (29% vs 58%). At 4–5 years of follow-up, relapses were mostly observed for patients diagnosed after 10 years old. <h3>Discussion</h3> In the included children, mostly of Afro-Caribbean and Sub-Saharan origin, sarcoidosis seems severe, with multi-organic involvement and foreground general symptoms. Common prognosis factors are not suitable in paediatric patients, and a young age at diagnosis does not seem to be associated with a poorer prognosis. The study is ongoing to provide further information on the very-long-term follow-up of paediatric sarcoidosis.
Estrogen Receptor Positive Breast Cancer Metastasis: Altered Hormonal Sensitivity and Tumor Aggressiveness in Lymphatic Vessels and Lymph Nodes
Authors: Joshua Chuck Harrell, Wendy W. Dye, D. Craig Allred, Paul Jedlicka, Nicole S. Spoelstra, Carol A. Sartorius, Kathryn B. Horwitz
Journal: Cancer Research (2006)

Abstract Breast cancers commonly spread to lymph nodes (LNs). If the primary tumors are estrogen receptor (ER) and/or progesterone receptor (PR) positive, then the likelihood that LN metastases express receptors exceeds 80%. However, due to lack of ER+ models, little is known about the role of hormones in breast cancer spread or the effects of the LN microenvironment on hormone responsiveness. We have developed metastasis models using ZsGreen labeled MCF-7 and T47D human breast cancer cells. Tumors are tracked in living mice by whole-body imaging, and macrometastases or micrometastases are detected by intravital imaging or fluorescence microscopy. Tumor growth is estrogen dependent and required for intratumoral lymphangiogenesis. Seventy-five percent of all tumors and &amp;gt;95% of larger tumors generate LN metastases. Occasionally more distant metastases are also observed. “Triads” of primary tumors, tumor-filled draining lymphatic vessels, and tumor-filled LNs from the same mouse show that (a) proliferation, as measured by 5-bromo-2′-deoxyuridine uptake, is higher in the LN than in the primary tumor. (b) High ER levels are extensively down-regulated by estradiol in primary tumors. However, there is partial failure of ER down-regulation in LNs associated with (c) reduced PR expression. This suggests that ER are dysfunctional in the LN microenvironment and perhaps hormone resistant. (d) CD44 is sparsely expressed in primary tumor cells but homogeneously overexpressed in cells transiting the lymphatics and populating LNs. We hypothesize that CD44 expression targets tumor cells for transport to, and uptake in, LNs. If so, the CD44 pathway could be targeted therapeutically to slow or prevent LN metastases. (Cancer Res 2006; 66(18): 9308-15)
Expression of Hedgehog Pathway Mediator <i>GLI</i> Represents a Negative Prognostic Marker in Human Acute Myeloid Leukemia and Its Inhibition Exerts Antileukemic Effects
Authors: Jasmin Wellbrock, Emily Latuske, Julian Köhler, Katharina Wagner, Hauke Stamm, Eik Vettorazzi, Gabi Vohwinkel, Marianne Klokow, Roswitha Uibeleisen, Patrick Ehm, Kristoffer Riecken, Sonja Loges, Felicitas Thol, Claudia Schubert, Michael Amling, Manfred Jücker, Carsten Bokemeyer, Michael Heuser, Jürgen Krauter, Walter Fiedler
Journal: Clinical Cancer Research (2015)

The Hedgehog pathway plays an important role in stem-cell biology and malignant transformation. Therefore, we investigated the expression and prognostic impact of Hedgehog pathway members in acute myeloid leukemia (AML).Pretreatment samples from 104 newly diagnosed AML patients (AMLSG 07-04 trial) were analyzed by qPCR, and expression of Hedgehog family members was correlated with clinical outcome. Inhibition of GLI by GANT61 or shRNA was investigated in AML cells in vitro and in vivo.Expression of receptors Smoothened and Patched-1 and their downstream mediators, GLI1, GLI2, and GLI3, was found in AML patients in contrast to Hedgehog ligands. GLI2 expression had a significant negative influence on event-free survival (EFS), relapse-free survival (RFS), and overall survival (OS; P = 0.037, 0.026, and 0.013, respectively) and was correlated with FLT3 mutational status (P < 0.001). Analysis of a second, independent patient cohort confirmed the negative impact of GLI2 on EFS and OS (P = 0.007 and 0.003, respectively; n = 290). Within this cohort, GLI1 had a negative prognostic impact (P < 0.001 for both EFS and OS). Although AML cells did not express Hedgehog ligands by qPCR, AML patients had significantly increased Desert Hedgehog (DHH) plasma levels compared with healthy subjects (P = 0.002), in whom DHH was presumably provided by bone marrow niche cells. Moreover, the GLI inhibitor GANT61 or knockdown of GLI1/2 by shRNA caused antileukemic effects, including induction of apoptosis, reduced proliferation, and colony formation in AML cells, and a survival benefit in mice.GLI expression is a negative prognostic factor and might represent a novel druggable target in AML.
Mitochondrial dysfunction in COPD patients with low body mass index
Authors: R. A. Rabinovich, R. Bastos, E. Ardite, L. Llinàs, M. Orozco-Levi, J. Gea, J. Vilaró, J. A. Barberà, R. Rodríguez-Roisin, J. C. Fernández-Checa, J. Roca
Journal: European Respiratory Journal (2006)

Patients with chronic obstructive pulmonary disease (COPD) show abnormal adaptations of skeletal muscle redox status after exercise training. Increased skeletal muscle oxidative stress in COPD patients may prompt mitochondrial dysfunction. The present study explores the association between body composition and mitochondrial respiration in seven COPD patients with low body mass index (BMI L ), eight COPD patients with normal body mass index (BMI N ) and seven healthy controls. All of them underwent a vastus lateralis biopsy in which muscle structure, in vitro mitochondrial respiratory function, uncoupling protein 3 (UCP3) mRNA expression and glutathione levels in both isolated mitochondria and the whole muscle were determined. Mitochondrial respiratory function (assessed by acceptor control ratio (ACR)) was impaired in BMI L (2.2±0.6) compared with both BMI N (5.3±1.3) and controls (8.2±1.3). ACR significantly correlated with arterial oxygen tension and with muscle endurance but it showed a negative association with exercise-induced increase in blood lactate levels. UCP3 mRNA expression was reduced in BMI L patients. In conclusion, chronic obstructive pulmonary disease patients with low body mass index show electron transport chain dysfunction, which may contribute to low muscle endurance in the current subgroup of patients.
Breast Cancer Incidence and Hormone Replacement Therapy in Canada
Authors: P. De, C. I. Neutel, I. Olivotto, H. Morrison
Journal: JNCI Journal of the National Cancer Institute (2010)

In 2002, results of the Women's Health Initiative clinical trial indicated that the long-term risks of combined estrogen and progestin hormone replacement therapy outweighed the health benefits for postmenopausal women. The resulting decline in use of hormone replacement therapy was followed by concurrent decreases in breast cancer incidence in several countries. The aim of the current study was to determine whether similar declines occurred in Canada.Data on prescriptions for hormone therapy were obtained from a national registry of pharmacy-filled prescriptions to confirm the reported trend in use of hormone replacement therapy among approximately 1200 women aged 50-69 years who participated in the National Population Health Survey between 1996 and 2006 and whose data were extrapolated to the Canadian female population. Age-standardized incidence rates for breast cancer were obtained from the population-based Canadian Cancer Registry for the same period, and mammography rates were obtained from the Canadian Community Health Survey. Joinpoint regression was used to examine changes in trends in the use of hormone replacement therapy and breast cancer incidence.A reduced frequency of use of hormone replacement therapy was reflected in the decrease in dispensed hormone therapy prescriptions after 2002. The largest drop in use of combined hormone replacement therapy (from 12.7%, 95% confidence interval [CI] = 10.1% to 14.2%, to 4.9%, 95% CI = 3.4% to 6.8%, of all women) occurred between January 1, 2002, and December 31, 2004, among women aged 50-69 years. This drop occurred concurrently with a 9.6% decline in the incidence rate of breast cancer (from 296.3 per 100,000 women, 95% CI = 290.8 to 300.5 per 100,000 women, in 2002 to 268.0 per 100,000 women, 95% CI = 263.3 to 273.5 per 100,000 women, in 2004). Mammography rates were stable at 72% over the same period.During the period 2002-2004, there was a link between the declines in the use of hormone replacement therapy and breast cancer incidence among Canadian women aged 50-69 years, in the absence of any change in mammography rates.
Impressive closure of a sustaining periprosthetic endoleak (type II) using fibrin glue application after former endovascular placement of an infrarenal aortic prosthesis
Authors: F. Meyer, J. Ricke, M. Pech, H. Lippert, Z. Halloul
Journal: International Journal of Surgery (2008)

ciates Ltd. Published by Elsevier Lt The management of a postinterventional endoleak after the endovascular repair of an aortic aneurysm is still a relevant problem through the patient’s postinterventional course. There are four types of endoleaks due to: (I) incomplete exclusion of the aneurysm; (II) retrograde filling of the aneurysmatic sac via the arteries originating from it; (III) defect of the endoprosthesis or dislocation of the endoprosthetic segments; and (IV) blood flow
The immunosuppressive fungal metabolite gliotoxin specifically inhibits transcription factor NF-kappaB.
Authors: H L Pahl, B Krauss, K Schulze-Osthoff, T Decker, E B Traenckner, M Vogt, C Myers, T Parks, P Warring, A Mühlbacher, A P Czernilofsky, P A Baeuerle
Journal: The Journal of Experimental Medicine (1996)

Opportunistic infections, such as aspergillosis, are among the most serious complications suffered by immunocompromised patients. Aspergillus fumigatus and other pathogenic fungi synthesize a toxic epipolythiodioxopiperazine metabolite called gliotoxin. Gliotoxin exhibits profound immunosuppressive activity in vivo. It induces apoptosis in thymocytes, splenocytes, and mesenteric lymph node cells and can selectively deplete bone marrow of mature lymphocytes. The molecular mechanism by which gliotoxin exerts these effects remains unknown. Here, we report that nanomolar concentrations of gliotoxin inhibited the activation of transcription factor NF-kappaB in response to a variety of stimuli in T and B cells. The effect of gliotoxin was specific because, at the same concentrations, the toxin did not affect activation of the transcription factor NF-AT or of interferon-responsive signal transducers and activators of transcription. Likewise, the activity of the constitutively DNA-binding transcription factors Oct-1 and cyclic AMP response element binding protein (CREB), as well as the activation of protein tyrosine kinases p56lck and p59fyn, was not altered by gliotoxin. Very high concentrations of gliotoxin prevented NF-kappaB DNA binding in vitro. However, in intact cells, inhibition of NF-kappaB did not occur at the level of DNA binding; rather, the toxin appeared to prevent degradation of IkappaB-alpha, NF-kappaB's inhibitory subunit. Our data raise the possibility that the immunosuppression observed during aspergillosis results in part from gliotoxin-mediated NF-kappaB inhibition.
Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis
Authors: P.G. Gibson, P.A.B. Wark, J.L. Simpson, C. Meldrum, S. Meldrum, N. Saltos, M. Boyle
Journal: European Respiratory Journal (2003)

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA. Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay. Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second. Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis.