tbuckley/cabot-search huggingface dataset:
Specific Migratory Dendritic Cells Rapidly Transport Antigen from the Airways to the Thoracic Lymph Nodes
Authors: Karim Y. Vermaelen, Ines Carro-Muino, Bart N. Lambrecht, Romain A. Pauwels
Journal: The Journal of Experimental Medicine (2000)

Antigen transport from the airway mucosa to the thoracic lymph nodes (TLNs) was studied in vivo by intratracheal instillation of fluorescein isothiocyanate (FITC)-conjugated macromolecules. After instillation, FITC+ cells with stellate morphology were found deep in the TLN T cell area. Using flow cytometry, an FITC signal was exclusively detected in CD11cmed-hi/major histocompatibility complex class II (MHCII)hi cells, representing migratory airway-derived lymph node dendritic cells (AW-LNDCs). No FITC signal accumulated in lymphocytes and in a CD11chiMHCIImed DC group containing a CD8αhi subset (non–airway-derived [NAW]-LNDCs). Sorted AW-LNDCs showed long MHCIIbright cytoplasmic processes and intracytoplasmatic FITC+ granules. The fraction of FITC+ AW-LNDCs peaked after 24 h and had reached baseline by day 7. AW-LNDCs were depleted by 7 d of ganciclovir treatment in thymidine kinase transgenic mice, resulting in a strong reduction of FITC-macromolecule transport into the TLNs. Compared with intrapulmonary DCs, AW-LNDCs had a mature phenotype and upregulated levels of MHCII, B7-2, CD40, and intracellular adhesion molecule (ICAM)-1. In addition, sorted AW-LNDCs from FITC-ovalbumin (OVA)–instilled animals strongly presented OVA to OVA-TCR transgenic T cells. These results validate the unique sentinel role of airway DCs, picking up antigen in the airways and delivering it in an immunogenic form to the T cells in the TLNs.
Synthesis of stress proteins is increased in individuals with homozygous PiZZ alpha 1-antitrypsin deficiency and liver disease.
Authors: D H Perlmutter, M J Schlesinger, J A Pierce, P I Punsal, A L Schwartz
Journal: Journal of Clinical Investigation (1989)

Individuals who are homozygous for the protease inhibitor phenotype Z (PiZ) genetic variant of alpha 1-antitrypsin (alpha 1-AT) have reduced plasma concentrations of alpha 1-AT, and are susceptible to premature development of pulmonary emphysema. A subset of this population develops chronic liver disease. The reduction in plasma concentrations of alpha 1-AT results from a selective defect in secretion as the abnormal PiZ alpha 1-AT protein accumulates within the cell. It has recently been shown in several experimental systems that the heat shock/stress response, a response characterized by the synthesis of a family of highly evolutionarily conserved proteins during thermal or chemical stress, may also be activated by the presence of abnormal proteins within the cell. Therefore, we predicted that the heat shock/stress response would be induced in the absence of thermal or chemical stress in alpha 1-AT-synthesizing cells of PiZZ individuals. In the following study, however, we show that net synthesis of proteins in the heat shock/stress gene family (SP90, SP70, ubiquitin) is increased only in a subset of the population, PiZZ individuals with liver disease. It is not significantly increased in PiZZ individuals with emphysema or in those without apparent tissue injury. Net synthesis of stress proteins is not increased in individuals with another variant of the alpha 1-AT gene (PiS alpha 1-AT) and is not increased in individuals with severe liver disease but a normal alpha 1-AT haplotype (PiM alpha 1-AT). These results demonstrate that the synthesis of stress proteins is increased in a subset of individuals with homozygous PiZZ alpha 1-AT deficiency, those also having liver disease.
Development and Progression of Renal Insufficiency With and Without Albuminuria in Adults With Type 1 Diabetes in the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications Study
Authors: Mark E. Molitch, Michael Steffes, Wanjie Sun, Brandy Rutledge, Patricia Cleary, Ian H. de Boer, Bernard Zinman, John Lachin
Journal: Diabetes Care (2010)

OBJECTIVE This multicenter study examined the impact of albumin excretion rate (AER) on the course of estimated glomerular filtration rate (eGFR) and the incidence of sustained eGFR &amp;lt;60 ml/min/1.73 m2 in type 1 diabetes up to year 14 of the Epidemiology of Diabetes Interventions and Complications (EDIC) study (mean duration of 19 years in the Diabetes Control and Complications Trial [DCCT]/EDIC). RESEARCH DESIGN AND METHODS Urinary albumin measurements from 4-h urine collections were obtained from participants annually during the DCCT and every other year during the EDIC study, and serum creatinine was measured annually in both the DCCT and EDIC study. GFR was estimated from serum creatinine using the abbreviated Modification of Diet in Renal Disease equation. RESULTS A total of 89 of 1,439 subjects developed an eGFR &amp;lt;60 ml/min/1.73 m2 (stage 3 chronic kidney disease on two or more successive occasions (sustained) during the DCCT/EDIC study (cumulative incidence 11.4%). Of these, 20 (24%) had AER &amp;lt;30 mg/24 h at all prior evaluations, 14 (16%) had developed microalbuminuria (AER 30–300 mg/24 h) before they reached stage 3 chronic kidney disease, and 54 (61%) had macroalbuminuria (AER &amp;gt;300 mg/24 h) before they reached stage 3 chronic kidney disease. Macroalbuminuria is associated with a markedly increased rate of fall in eGFR (5.7%/year vs. 1.2%/year with AER &amp;lt;30 mg/24 h, P &amp;lt; 0.0001) and risk of eGFR &amp;lt;60 ml/min/1.73 m2 (adjusted hazard ratio 15.3, P &amp;lt; 0.0001), whereas microalbuminuria had weaker and less consistent effects on eGFR. CONCLUSIONS Macroalbuminuria was a strong predictor of eGFR loss and risk of developing sustained eGFR &amp;lt;60 ml/min/1.73 m2. However, screening with AER alone would have missed 24% of cases of sustained impaired eGFR.
Effect of 48 Hours of Nitric Oxide Inhalation on Pulmonary Vasoreactivity in Rats
Authors: XAVIER COMBES, MICHEL MAZMANIAN, HERVÉ GOURLAIN, PHILIPPE HERVÉ
Journal: American Journal of Respiratory and Critical Care Medicine (1997)

Nitric oxide (NO) has been shown to down regulate its own synthesis in vitro. We tested the hypothesis that NO inhalation (30 ppm under normoxic conditions) could decrease the release of endogenous endothelial NO, and thus alter pulmonary vasoreactivity. Pulmonary vasoreactivity was assessed in isolated perfused rat lungs immediately or 6 h after a 48 h NO inhalation period, and compared with a control group. NO inhalation resulted in an increase in pulmonary vasoconstrictor reactivity to angiotensine II and U-46619, a reduction in the potentiation by the eNOS inhibitor L-NAME of the angiotensine II response, a decrease in endothelium-dependent vasodilation to arginine vasopressin, whereas non–endothelium-dependent vasodilation to sodium nitroprusside remained unaltered. These alterations returned to control values in the group studied 6 h after the end of NO inhalation, and were not prevented by inhibition of the prostanoid synthesis, or by pretreatment with the endothelin receptors antagonist Bosentan. These results indicate that NO inhalation over 2 d induces a reversible alteration of pulmonary vasoreactivity in relationship with a decrease in endogenous NO release. Inhibition of eNOS could be involved.
Adenovirus-mediated increase in HNF-3β or HNF-3α shows differences in levels of liver glycogen and gene expression
Authors: Yongjun Tan, Douglas Hughes, Xinhe Wang, Robert H. Costa
Journal: Hepatology (2002)

We previously generated a transgenic mouse line (T-77) in which increased hepatic expression of the hepatocyte nuclear factor-3beta (HNF-3beta) protein was used to assess its role in hepatocyte-specific gene transcription. The T-77 transgenic mice displayed elevated serum bile acid and bilirubin levels and a complete absence of hepatic glycogen storage. These postnatal liver defects were associated with diminished expression of hepatocyte genes involved in gluconeogenesis and bile acid transport as well as reduced levels of hepatocyte transcription factors. In this study, we show that mouse tail vein injections of adenovirus expressing the rat HNF-3beta (AdHNF3beta) cDNA efficiently increased its levels throughout the liver lobule and recapitulated the T-77 transgenic liver phenotype within several days postinfection. Likewise, the AdHNF3beta-infected liver phenotype was associated with reduced hepatic expression of genes involved in glucose homeostasis, bile acid transport, and bilirubin conjugation, which were not found with control adenovirus infections. These studies show that adenovirus-mediated gene transfer is an effective method for rapid hepatic increases in transcription factor levels to determine in vivo target genes. In contrast, AdHNF3alpha-infected liver displayed only a transient reduction in hepatic glycogen levels and was associated with less severe decreases in hepatic expression of gluconeogenic and bilirubin metabolism genes. Consistent with these findings, only T-77 transgenic and AdHNF3beta-infected liver exhibited diminished hepatic expression of the HNF-6 transcription factor, suggesting that reduced HNF-6 levels contribute to diminished HNF-3beta-specific transcriptional activity.
Dual Function of ERRα in Breast Cancer and Bone Metastasis Formation: Implication of VEGF and Osteoprotegerin
Authors: Anaïs Fradet, Helène Sorel, Lamia Bouazza, Delphine Goehrig, Baptiste Dépalle, Akeila Bellahcène, Vincent Castronovo, Hélène Follet, Françoise Descotes, Jane E. Aubin, Philippe Clézardin, Edith Bonnelye
Journal: Cancer Research (2011)

Bone metastasis is a complication occurring in up to 70% of advanced breast cancer patients. The estrogen receptor-related receptor alpha (ERRα) has been implicated in breast cancer and bone development, prompting us to examine whether ERRα may function in promoting the osteolytic growth of breast cancer cells in bone. In a mouse xenograft model of metastatic human breast cancer, overexpression of wild-type ERRα reduced metastasis, whereas overexpression of a dominant negative mutant promoted metastasis. Osteoclasts were directly affected and ERRα upregulated the osteoclastogenesis inhibitor, osteoprotegerin (OPG), providing a direct mechanistic basis for understanding how ERRα reduced breast cancer cell growth in bone. In contrast, ERRα overexpression increased breast cancer cell growth in the mammary gland. ERRα-overexpressing primary tumors were highly vascularized, consistent with an observed upregulation of angiogenic growth factor, the VEGF. In support of these findings, we documented that elevated expression of ERRα mRNA in breast carcinomas was associated with high expression of OPG and VEGF and with disease progression. In conclusion, our results show that ERRα plays a dual role in breast cancer progression in promoting the local growth of tumor cells, but decreasing metastatic growth of osteolytic lesions in bone.
MTG16 contributes to colonic epithelial integrity in experimental colitis
Authors: Christopher S Williams, Amber M Bradley, Rupesh Chaturvedi, Kshipra Singh, Maria B Piazuelo, Xi Chen, Elizabeth M McDonough, David A Schwartz, Caroline T Brown, Margaret M Allaman, Lori A Coburn, Sara N Horst, Dawn B Beaulieu, Yash A Choksi, Mary Kay Washington, Amanda D Williams, Melissa A Fisher, Sandra S Zinkel, Richard M Peek, Keith T Wilson, Scott W Hiebert
Journal: Gut (2012)

<h3>Objective</h3> The myeloid translocation genes (MTGs) are transcriptional corepressors with both <i>Mtg8<sup>−/−</sup></i> and <i>Mtgr1<sup>−/−</sup></i> mice showing developmental and/or differentiation defects in the intestine. We sought to determine the role of MTG16 in intestinal integrity. <h3>Methods</h3> Baseline and stress induced colonic phenotypes were examined in <i>Mtg16<sup>−/−</sup></i> mice. To unmask phenotypes, we treated <i>Mtg16<sup>−/−</sup></i> mice with dextran sodium sulphate (DSS) or infected them with <i>Citrobacter rodentium</i> and the colons were examined for ulceration and for changes in proliferation, apoptosis and inflammation. <h3>Results</h3> <i>Mtg16<sup>−/−</sup></i> mice have altered immune subsets, suggesting priming towards Th1 responses. <i>Mtg16<sup>−/−</sup></i> mice developed increased weight loss, diarrhoea, mortality and histological colitis and there were increased innate (Gr1<sup>+</sup>, F4/80<sup>+</sup>, CD11c<sup>+</sup> and MHCII<sup>+</sup>; CD11c<sup>+</sup>) and Th1 adaptive (CD4) immune cells in <i>Mtg16<sup>−/−</sup></i> colons after DSS treatment. Additionally, there was increased apoptosis and a compensatory increased proliferation in <i>Mtg16<sup>−/−</sup></i> colons. Compared with wild-type mice, <i>Mtg16<sup>−/−</sup></i> mice exhibited increased colonic CD4;IFN-γ cells in vehicle-treated and DSS-treated mice. Adoptive transfer of wild-type marrow into <i>Mtg16<sup>−/−</sup></i> recipients did not rescue the <i>Mtg16<sup>−/−</sup></i> injury phenotype. Isolated colonic epithelial cells from DSS-treated <i>Mtg16<sup>−/−</sup></i> mice exhibited increased KC (Cxcl1) mRNA expression when compared with wild-type mice. <i>Mtg16<sup>−/−</sup></i> mice infected with <i>C rodentium</i> had more severe colitis and greater bacterial colonisation. Last, <i>MTG16</i> mRNA levels were reduced in human ulcerative colitis versus normal colon tissues. <h3>Conclusions</h3> These observations indicate that MTG16 is critical for colonocyte survival and regeneration in response to intestinal injury and provide evidence that this transcriptional corepressor regulates inflammatory recruitment in response to injury.
Saccular intracranial aneurysms in autosomal dominant polycystic kidney disease.
Authors: W I Schievink, V E Torres, D G Piepgras, D O Wiebers
Journal: Journal of the American Society of Nephrology (1992)

The literature on the association of intracranial aneurysms in autosomal dominant polycystic kidney disease (ADPKD) consists mainly of case reports and small series of patients. To provide a more-detailed description of this association and its frequency, the records of all ADPKD patients with saccular intracranial aneurysms, all ADPKD autopsy cases including brain examination, and sex- and age-matched autopsy cases without ADPKD seen at the Mayo Clinic between 1950 and 1989 and of all Rochester residents with a diagnosis of subarachnoid hemorrhage or ADPKD between 1945 and 1984 were reviewed. The presentation of the 41 patients (22 men and 19 women; mean age, 46.4 yr) with this association was subarachnoid hemorrhage in 33, transient ischemic attacks in 2, incidental angiographic or autopsy finding in 5, and discovery during angiographic screening in 1. Thirty-one, seven, and three patients harbored one, two, and three aneurysms, respectively, arising from the middle cerebral artery (N = 23), anterior communicating artery (N = 16), internal carotid artery (N = 11), and vertebral or basilar artery (N = 4). A family history of intracranial aneurysm, subarachnoid hemorrhage, or intracranial hemorrhage at an early age was present in 22% of the patients. Small aneurysms (less than 5 mm) were less likely to have ruptured or caused symptoms (P less than 0.04). There was a trend for hypertension to be associated with the severity of the subarachnoid hemorrhage. Aneurysmal rupture occurred before age 50 in 64% of patients. Of the 89 ADPKD autopsy cases with brain examination, 22.5% had intracranial aneurysms.(ABSTRACT TRUNCATED AT 250 WORDS)
EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) is sensitive to show efficacy of rituximab treatment in a randomised controlled trial
Authors: R V Moerman, S Arends, P M Meiners, E Brouwer, F K L Spijkervet, F G M Kroese, A Vissink, H Bootsma
Journal: Annals of the Rheumatic Diseases (2013)

Rituximab therapy is a promising treatment for primary Sjogren's syndrome (pSS).1 ,2 So far, treatment studies performed in patients with pSS lacked the use of a uniform outcome measure to monitor disease activity.

Recently, the European League Against Rheumatism (EULAR) developed the EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI).3 ESSDAI was shown to be able to monitor disease activity in patient profile and open-label studies.4 ,5 To further study the utility of ESSDAI for clinical studies, we assessed the responsiveness of ESSDAI after rituximab treatment in a randomised controlled trial (RCT) of patients with pSS.6 

As the principal investigator (HB) was involved in the development of ESSDAI, the database of a single-centre, randomised, double-blind, placebo-controlled trial (see ref. 6 for details) was prospectively completed with regard to all ESSDAI domains, namely the cutaneous, respiratory, renal, articular, muscular, peripheral and central nervous system, haematological, glandular, constitutional, …
Clearance of influenza virus from the lung depends on migratory langerin+CD11b− but not plasmacytoid dendritic cells
Authors: Corine H. GeurtsvanKessel, Monique A.M. Willart, Leonie S. van Rijt, Femke Muskens, Mirjam Kool, Chantal Baas, Kris Thielemans, Clare Bennett, Björn E. Clausen, Henk C. Hoogsteden, Albert D.M.E. Osterhaus, Guus F. Rimmelzwaan, Bart N. Lambrecht
Journal: The Journal of Experimental Medicine (2008)

Although dendritic cells (DCs) play an important role in mediating protection against influenza virus, the precise role of lung DC subsets, such as CD11b− and CD11b+ conventional DCs or plasmacytoid DCs (pDCs), in different lung compartments is currently unknown. Early after intranasal infection, tracheal CD11b−CD11chi DCs migrated to the mediastinal lymph nodes (MLNs), acquiring co-stimulatory molecules in the process. This emigration from the lung was followed by an accumulation of CD11b+CD11chi DCs in the trachea and lung interstitium. In the MLNs, the CD11b+ DCs contained abundant viral nucleoprotein (NP), but these cells failed to present antigen to CD4 or CD8 T cells, whereas resident CD11b−CD8α+ DCs presented to CD8 cells, and migratory CD11b−CD8α− DCs presented to CD4 and CD8 T cells. When lung CD11chi DCs and macrophages or langerin+CD11b−CD11chi DCs were depleted using either CD11c–diphtheria toxin receptor (DTR) or langerin-DTR mice, the development of virus-specific CD8+ T cells was severely delayed, which correlated with increased clinical severity and a delayed viral clearance. 120G8+ CD11cint pDCs also accumulated in the lung and LNs carrying viral NP, but in their absence, there was no effect on viral clearance or clinical severity. Rather, in pDC-depleted mice, there was a reduction in antiviral antibody production after lung clearance of the virus. This suggests that multiple DCs are endowed with different tasks in mediating protection against influenza virus.
NUMTs in Sequenced Eukaryotic Genomes
Authors: E. Richly
Journal: Molecular Biology and Evolution (2004)

Mitochondrial DNA sequences are frequently transferred to the nucleus giving rise to the so-called nuclear mitochondrial DNA (NUMT). Analysis of 13 eukaryotic species with sequenced mitochondrial and nuclear genomes reveals a large interspecific variation of NUMT number and size. Copy number ranges from none or few copies in Anopheles, Caenorhabditis, Plasmodium, Drosophila, and Fugu to more than 500 in human, rice, and Arabidopsis. The average size is between 62 (baker's yeast) and 647 bps (Neurospora), respectively. A correlation between the abundance of NUMTs and the size of the nuclear or the mitochondrial genomes, or of the nuclear gene density, is not evident. Other factors, such as the number and/or stability of mitochondria in the germline, or species-specific mechanisms controlling accumulation/loss of nuclear DNA, might be responsible for the interspecific diversity in NUMT accumulation.
Associations between Traffic-Related Black Carbon Exposure and Attention in a Prospective Birth Cohort of Urban Children
Authors: Yueh-Hsiu Mathilda Chiu, David C. Bellinger, Brent A. Coull, Shawn Anderson, Rachel Barber, Robert O. Wright, Rosalind J. Wright
Journal: Environmental Health Perspectives (2013)

Background: Ambient air pollution may have neurotoxic effects in children. Data examining associations between traffic-related air pollution and attention domains remain sparse.Objectives: We examined associations between black carbon (BC), a marker of traffic particles, and attention measures ascertained at 7–14 years of age among 174 children in a birth cohort based in the Boston, Massachusetts, area.Methods: We estimated BC levels using a validated spatial–temporal land-use regression model based on residence during children’s lifetime. Children completed the Conner’s Continuous Performance Test (CPT) measuring omission errors, commission errors, and hit reaction time (HRT), with higher scores indicating increased errors or slower reaction time. Multivariable-adjusted linear regression analyses were used to examine associations between BC and each attention outcome.Results: Children were primarily Hispanic (56%) and Caucasian (41%); 53% were boys. We found a positive association between higher BC levels with increased commission errors and slower HRT, adjusting for child IQ, age, sex, blood lead level, maternal education, pre- and postnatal tobacco smoke exposure, and community-level social stress. Notably, the association was weaker, though still positive, for the highest BC quartile relative to the middle two quartiles. Sex-stratified analysis demonstrated statistically significant associations between BC and both commission errors and HRT in boys, but BC was not significantly associated with any of the CPT outcomes in girls.Conclusions: In this population of urban children, we found associations between BC exposure and higher commission errors and slower reaction time. These associations were overall more apparent in boys than girls.
Docetaxel and pegylated liposomal doxorubicin combination as first-line therapy for metastatic breast cancer patients: results of the phase II GINECO trial CAPYTTOLE
Authors: C. de la Fouchardière, R. Largillier, Y. Goubely, A.-C. Hardy-Bessard, B. Slama, J. Cretin, H. Orfeuvre, D. Paraiso, T. Bachelot, E. Pujade-Lauraine
Journal: Annals of Oncology (2009)

This phase II study evaluated the clinical benefit of pegylated liposomal doxorubicin (PLD) and docetaxel (Taxotere) as first-line therapy for metastatic breast cancer (MBC).MBC patients were enrolled to receive six cycles of PLD 35 mg/m2 (day 1) and docetaxel 40 mg/m2 (days 1 and 15), every 28 days (group A). Because of unacceptable toxic effects, doses were modified to PLD 30 mg/m2 (day 1) and docetaxel 75 mg/m2 (day 2), every 3 weeks (group B). The primary end point was clinical benefit.Sixty-seven patients were included (group A, 53; group B, 14). In both groups, the median number of cycles delivered was 4 and the overall dose intensity was 82% for docetaxel and 71% for PLD. In group A, main toxic effects were hematologic, palmar-plantar erythrodysesthesia (PPE), and stomatitis. In group B, higher rates of grade 3-4 PPE, febrile neutropenia, and hematologic toxic effects were reported. The rate of clinical benefit was 47%. Among patients with a measurable disease, 49% achieved a partial response, 27% had a stable disease, and 13% progressed, according to RECIST criteria.The combination of PLD and docetaxel delivered at planned doses in this study yields unacceptable toxicity and should not be used routinely in patients with MBC.
“Mind is brain” is trivial and nonscientific in both neurobiology and cognitive science
Authors: J. Scott Jordan
Journal: Behavioral and Brain Sciences (1999)

Gold &amp; Stoljar reveal that adherence to the radical neuron doctrine cannot be maintained via appeals to scientific principles. Using arguments from (1) naturalism and materialism, (2) unification, and (3) exemplars, it is shown that the “mind-is-brain” materialism explicit in the trivial version of the neuron doctrine ultimately suffers the same theoretical fate. Cognitive science, if it is to adopt an ontology at all, would be better served by a metaphysically neutral ontology such as double-aspect theory or neutral monism.