tbuckley/cabot-search huggingface dataset:
Rheumatoid arthritis subtypes identified by genomic profiling of peripheral blood cells: assignment of a type I interferon signature in a subpopulation of patients
Authors: T C T M van der Pouw Kraan, C A Wijbrandts, L G M van Baarsen, A E Voskuyl, F Rustenburg, J M Baggen, S M Ibrahim, M Fero, B A C Dijkmans, P P Tak, C L Verweij
Journal: Annals of the Rheumatic Diseases (2007)

<b>Background:</b> Rheumatoid arthritis (RA) is a heterogeneous disease with unknown cause. <b>Aim:</b> To identify peripheral blood (PB) gene expression profiles that may distinguish RA subtypes. <b>Methods:</b> Large-scale expression profiling by cDNA microarrays was performed on PB from 35 patients and 15 healthy individuals. Differential gene expression was analysed by significance analysis of microarrays (SAM), followed by gene ontology analysis of the significant genes. Gene set enrichment analysis was applied to identify pathways relevant to disease. <b>Results:</b> A substantially raised expression of a spectrum of genes involved in immune defence was found in the PB of patients with RA compared with healthy individuals. SAM analysis revealed a highly significant elevated expression of interferon (IFN) type I regulated genes in patients with RA compared with healthy individuals, which was confirmed by gene ontology and pathway analysis, suggesting that this pathway was activated systemically in RA. A quantitative analysis revealed that increased expression of IFN-response genes was characteristic of approximately half of the patients (IFN<sup>high</sup> patients). Application of pathway analysis revealed that the IFN<sup>high</sup> group was largely different from the controls, with evidence for upregulated pathways involved in coagulation and complement cascades, and fatty acid metabolism, while the IFN<sup>low</sup> group was similar to the controls. <b>Conclusion:</b> The IFN type I signature defines a subgroup of patients with RA, with a distinct biomolecular phenotype, characterised by increased activity of the innate defence system, coagulation and complement cascades, and fatty acid metabolism.
STAT3: A critical transcription activator in angiogenesis
Authors: Zhong Chen, Zhong Chao Han
Journal: Medicinal Research Reviews (2007)

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is a complex multistage process regulated by a number of signal transduction pathways. Accumulating evidence suggests that signal transducer and activator of transcription (STATs), mainly STAT3, play an important role in angiogenesis under both physiological and pathological conditions in addition to cell survival, proliferation, differentiation, and oncogenesis. STAT3, as a critical multifunctional mediator, regulates many aspects of angiogenesis at the transcriptional level. This review will highlight the pivotal role of STAT3 in well-studied tumorous angiogenesis and cardiac angiogenesis, and summarize various potential mechanisms utilized by STAT3 to regulate the transcriptional activation of VEGF.
Both Donor and Recipient Origins of Smooth Muscle Cells in Vein Graft Atherosclerotic Lesions
Authors: Yanhua Hu, Manuel Mayr, Bernhard Metzler, Martin Erdel, Fergus Davison, Qingbo Xu
Journal: Circulation Research (2002)

Smooth muscle cell (SMC) accumulation in the inner layer of the vessel wall is a key event in the pathogenesis of atherosclerosis in vein grafts, but the origin of the cells in these lesions has yet to be shown. Herein, we use animal models of vein grafts in transgenic mice to clearly identify the sources of SMCs in atherosclerosis. Vena cava segments were isografted to carotid arteries between four types of transgenic mice, including SM-LacZ expressing beta-galactosidase (beta-gal) in vascular SMCs, SM-LacZ/apoE(-/-), ROSA26 expressing beta-gal in all tissues, and wild-type mice. beta-gal-positive cells were observed in neointimal and atherosclerotic lesions of all vein segments grafted between LacZ transgenic and wild-type mice. Double staining for beta-gal and cell nuclei revealed that about 40% of SMCs originated from hosts and 60% from the donor vessel. This was confirmed by double labeling of the Y-chromosome and alpha-actin in the lesions of sex-mismatched vein grafts. The possibility that bone marrow cells were the source of SMCs in grafts was eliminated by the absence of beta-gal staining in atherosclerotic lesions of chimeric mice. Furthermore, vein SMCs of SM-LacZ mice did not express beta-gal in situ, but did so when these cells appeared in atherosclerotic lesions in vivo, suggesting that hemodynamic forces may be crucial for SMC differentiation. Thus, we provide the first evidence of SMC origins in the atherosclerotic lesions of vein grafts, which will be essential for providing insight into new types of therapy for the disease. The full text of this article is available at http://www.circresaha.org.
Degradation of Transcription Factor Rfx5 during the Inhibition of Both Constitutive and Interferon γ–Inducible Major Histocompatibility Complex Class I Expression in Chlamydia-Infected Cells
Authors: Guangming Zhong, Li Liu, Tao Fan, Peiyi Fan, Hezhao Ji
Journal: The Journal of Experimental Medicine (2000)

We have previously shown that the obligate intracellular pathogen chlamydia can suppress interferon (IFN)-γ–inducible major histocompatibility complex (MHC) class II expression in infected cells by degrading upstream stimulation factor (USF)-1. We now report that chlamydia can also inhibit both constitutive and IFN-γ–inducible MHC class I expression in the infected cells. The inhibition of MHC class I molecule expression correlates well with degradation of RFX5, an essential downstream transcription factor required for both the constitutive and IFN-γ–inducible MHC class I expression. We further demonstrate that a lactacystin-sensitive proteasome-like activity identified in chlamydia-infected cell cytosolic fraction can degrade both USF-1 and RFX5. This proteasome-like activity is dependent on chlamydial but not host protein synthesis. Host preexisting proteasomes may not be required for the unique proteasome-like activity. These observations suggest that chlamydia-secreted factors may directly participate in the proteasome-like activity. Efforts to identify the chlamydial factors are underway. These findings provide novel information on the molecular mechanisms of chlamydial evasion of host immune recognition.
Growth Hormone Responses to Thyroid Hormone in the Neonatal Rat
Authors: Hisao Seo, Caryn Wunderlich, Gilbert Vassart, Samuel Refetoff
Journal: Journal of Clinical Investigation (1981)

Differences in the growth hormone (GH) responses to primary and to secondary stimulation with triiodothyronine (T3) were studied in rats deprived of thyroid hormone from birth. Neonatal hypothyroidism was induced in pups by feeding pregnant rats an iodine-deficient, propylthiouracil-containing diet. T3 stimulation was carried out in pups by subcutaneous injection of a single dose of 50 μg T3/100 g body wt. Pituitary GH content, rate of GH synthesis in vitro, and GH messenger (m)RNA activity in a cellfree translation system were measured.
Can Involuntary Outpatient Commitment Reduce Hospital Recidivism?: Findings From a Randomized Trial With Severely Mentally Ill Individuals
Authors: Marvin S. Swartz, Jeffrey W. Swanson, H. Ryan Wagner, Barbara J. Burns, Virginia A. Hiday, Randy Borum
Journal: American Journal of Psychiatry (1999)

The goal of this study was to evaluate the effectiveness of involuntary outpatient commitment in reducing rehospitalizations among individuals with severe mental illnesses.Subjects who were hospitalized involuntarily were randomly assigned to be released (N = 135) or to continue under outpatient commitment (N = 129) after hospital discharge and followed for 1 year. Each subject received case management services plus additional outpatient treatment. Outpatient treatment and hospital use data were collected.In bivariate analyses, the control and outpatient commitment groups did not differ significantly in hospital outcomes. However, subjects who underwent sustained periods of outpatient commitment beyond that of the initial court order had approximately 57% fewer readmissions and 20 fewer hospital days than control subjects. Sustained outpatient commitment was shown to be particularly effective for individuals with nonaffective psychotic disorders, reducing hospital readmissions approximately 72% and requiring 28 fewer hospital days. In repeated measures multivariable analyses, the outpatient commitment group had significantly better hospital outcomes, even without considering the total length of court-ordered outpatient commitments. However, in subsequent repeated measures analyses examining the role of outpatient treatment among psychotically disordered individuals, it was also found that sustained outpatient commitment reduced hospital readmissions only when combined with a higher intensity of outpatient treatment.Outpatient commitment can work to reduce hospital readmissions and total hospital days when court orders are sustained and combined with intensive treatment, particularly for individuals with psychotic disorders. This use of outpatient commitment is not a substitute for intensive treatment; it requires a substantial commitment of treatment resources to be effective.
Cirrhosis ameliorates monocrotaline-induced pulmonary hypertension in rats
Authors: J. Le Pavec, F. Perros, S. Eddahibi, B. Decante, P. Dorfmuller, O. Sitbon, D. Lebrec, M. Humbert, M. Mazmanian, P. Herve
Journal: European Respiratory Journal (2009)

Common bile duct ligation (CBDL) induces biliary cirrhosis and pulmonary vasodilatation. We tested whether CBDL ameliorates monocrotaline (MCT)-induced pulmonary hypertension (PH) in rats. Five groups of rats were studied: controls; rats dosed with MCT (60 mg.kg(-1) subcutaneously); CBDL; rats dosed with MCT followed by CBDL on day 7; and rats dosed with MCT followed by CBDL (day 7) and L-NAME therapy between days 24 and 28. 28-day survival was 26% in the MCT group and 72% in the MCT+CBDL group. Pulmonary vascular resistance measured on days 21 and 28 increased in the MCT and MCT+CBDL+L-NAME groups, but returned to normal in the MCT+CBDL group on day 28. Pulmonary artery (PA) medial hypertrophy persisted in MCT+CBDL rats. PA inflammation increased in MCT+CBDL rats, with accumulation of both intra- and perivascular macrophages. Exhaled nitric oxide (NO) levels decreased in the MCT group and increased in the MCT+CBDL group, which showed upregulation of inducible NO synthase and normal endothelial NO synthase. Blood endothelin (ET)-1 increased in CBDL, MCT, and MCT+CBDL rats. Levels of ET(B) receptors increased and ET(A) receptors decreased in the MCT+CBDL group, whereas the opposite changes occurred in the MCT group. Biliary cirrhosis induces pulmonary vasodilation that ameliorates MCT-induced PH and improves survival. Upregulation of inducible NO synthase and ET(B) receptor and downregulation of ET(A) receptor may be involved.
Weird people, yes, but also weird experiments
Authors: Nicolas Baumard, Dan Sperber
Journal: Behavioral and Brain Sciences (2010)

Abstract While we agree that the cultural imbalance in the recruitment of participants in psychology experiments is highly detrimental, we emphasize the need to complement this criticism with a warning about the “weirdness” of some cross-cultural studies showing seemingly deep cultural differences. We take the example of economic games and suggest that the variety of results observed in these games may not be due to deep psychological differences per se, but rather due to different interpretations of the situation.
Quantitative Determination of the Urinary Cortisolc Metabolites, “Tetrahydro F,” “Allo-Tetrahydro F” and “Tetrahydro E”: Effects of Adrenocorticotropin and Complex Trauma in the Human1
Authors: Norman I. Gold, Elaine Singleton, David A. Macfarlane, Francis D. Moore
Journal: Journal of Clinical Investigation (1958)
Signaling by IL-6 promotes alternative activation of macrophages to limit endotoxemia and obesity-associated resistance to insulin
Authors: Jan Mauer, Bhagirath Chaurasia, Julia Goldau, Merly C Vogt, Johan Ruud, Khoa D Nguyen, Sebastian Theurich, A Christine Hausen, Joel Schmitz, Hella S Brönneke, Emma Estevez, Tamara L Allen, Andrea Mesaros, Linda Partridge, Mark A Febbraio, Ajay Chawla, F Thomas Wunderlich, Jens C Brüning
Journal: Nature Immunology (2014)
Long-Term Evolutionary Stability of Bacterial Endosymbiosis in Curculionoidea: Additional Evidence of Symbiont Replacement in the Dryophthoridae Family
Authors: Cyrille Conord, Laurence Despres, Agnès Vallier, Séverine Balmand, Christian Miquel, Stéphanie Zundel, Guy Lemperiere, Abdelaziz Heddi
Journal: Molecular Biology and Evolution (2008)

Bacterial intracellular symbiosis (endosymbiosis) is well documented in the insect world where it is believed to play a crucial role in adaptation and evolution. However, although Coleopteran insects are of huge ecological and economical interest, endosymbiont molecular analysis is limited to the Dryophthoridae family. Here, we have analyzed the intracellular symbiotic bacteria in 2 Hylobius species belonging to the Molytinae subfamily (Curculionoidea superfamily) that exhibit different features from the Dryophthoridae insects in terms of their ecology and geographical spanning. Fluorescence in situ hybridization has shown that both Hylobius species harbor rod-shaped pleiomorphic symbiotic bacteria in the oocyte and in the bacteria-bearing organ (the bacteriome), with a shape and location similar to those of the Dryophthoridae bacteriome. Phylogenetic analysis of the 16S ribosomal DNA gene sequences, using the heterogeneous model of DNA evolution, has placed the Hylobius spp. endosymbionts (H-group) at the basal position of the ancestral R-clade of Dryophthoridae endosymbionts named Candidatus Nardonella but relatively distant from the S-clade of Sitophilus spp. endosymbionts. Endosymbionts from the H-group and the R-clade evolved more quickly compared with free-living enteric bacteria and endosymbionts from the S- and D-clades of Dryophthoridae. They are AT biased (58.3% A + T), and they exhibit AT-rich insertions at the same position as previously described in the Candidatus Nardonella 16S rDNA sequence. Moreover, the host phylogenetic tree based on the mitochondrial COI gene was shown to be highly congruent with the H-group and the R-clade, the divergence of which was estimated to be around 125 MYA. These new molecular data show that endosymbiosis is old in Curculionids, going back at least to the common ancestor of Molytinae and Dryophthoridae, and is evolutionary stable, except in 2 Dryophthoridae clades, providing additional and independent supplementary evidence for endosymbiont replacement in these taxa.
Cardiac Sympathetic Dysautonomia in Chronic Orthostatic Intolerance Syndromes
Authors: David S. Goldstein, Courtney Holmes, Steven M. Frank, Raghuveer Dendi, Richard O. Cannon, Yehonatan Sharabi, Murray D. Esler, Graeme Eisenhofer
Journal: Circulation (2002)

In postural tachycardia syndrome (POTS) and repeated neurocardiogenic presyncope (NCS), orthostatic intolerance occurs without persistent sympathetic neurocirculatory failure. Whether these conditions involve abnormal cardiac sympathetic innervation or function has been unclear.Patients with POTS or NCS underwent measurements of neurochemical indices of cardiac release, reuptake, and synthesis of the sympathetic neurotransmitter norepinephrine based on entry of norepinephrine into the cardiac venous drainage (cardiac norepinephrine spillover), cardiac extraction of circulating (3)H-norepinephrine, and cardiac production of dihydroxyphenylalanine and measurement of left ventricular myocardial innervation density using 6-[(18)F]fluorodopamine positron emission tomographic scanning. Mean cardiac norepinephrine spillover in POTS (171+/-30 pmol/min, N=16) was higher and in NCS (62+/-9 pmol/min, N=20) was lower than in a large group of healthy volunteers (102+/-9 pmol/min, N=52) and in a subgroup of age-matched healthy women (106+/-18 pmol/min, N=11). Both patient groups had normal cardiac extraction of (3)H-norepinephrine, normal cardiac production of dihydroxyphenylalanine, and normal myocardial 6-[(18)F]fluorodopamine-derived radioactivity.POTS and NCS differ in tonic cardiac sympathetic function, with increased cardiac norepinephrine release in the former and decreased release in the latter. Both groups had normal values for indices of function of the cell membrane norepinephrine transporter, norepinephrine synthesis, and density of myocardial sympathetic innervation. Because POTS and NCS both include specific abnormalities of cardiac sympathetic function, both can be considered forms of dysautonomia.
The Role of CXCR4 in Maintaining Peripheral B Cell Compartments and Humoral Immunity
Authors: Yuchun Nie, Janelle Waite, Faraha Brewer, Mary-Jean Sunshine, Dan R. Littman, Yong-Rui Zou
Journal: The Journal of Experimental Medicine (2004)

The chemokine receptor CXCR4 is expressed in B cells at multiple stages of their development. CXCR4 function in humoral immunity has not been fully investigated. We have generated gene-targeted mice in which CXCR4 can be selectively inactivated in B cells and have shown that it is required for retention of B cell precursors in the bone marrow. CXCR4-deficient B cell precursors that migrated prematurely became localized in splenic follicles despite their unresponsiveness to CXCL13. Concomitantly, mature B cell populations were reduced in the splenic marginal zone and primary follicles, and in the peritoneal cavity in the mutant animals, as were T-independent antibody responses. In addition, aberrant B cell follicles formed ectopically in intestinal lamina propria around Peyer's patches. These findings establish an important role for CXCR4 in regulating homeostasis of B cell compartmentalization and humoral immunity.
Inhibitory action of 711389-S on the electrical activity of rabbit sinoatrial node
Authors: H. KOTAKE, I. HISATOME, J. HASEGAWA, J. YAMASAKI, T. KOSAKA, T. FURUSE, H. MASHIBA
Journal: Cardiovascular Research (1987)

The effects of 711389-S (0.1-10 μmol·litre−1) on membrane potentials and currents of rabbit sinoatrial node preparations were studied using a conventional double microelectrode voltage-clamp method. The agent 711389-S decreased the heart rate, the maximum rate of depolarisation, and the amplitude of the action potential and increased the action potential duration in a dose dependent manner. The slope of the diastolic depolarisation was also reduced. Of the current systems of sinoatrial node, 711389-S depressed the slow inward current (Isi), the potassium outward current (IK), and the hyperpolarisation activated current (Ih) dose dependently. The kinetics of IK were not altered significantly by the drug. It is concluded that 711389-S does not have an effect on a single current system but that the drug exerts a depressant effect on the electrical activity of the sinoatrial node.
<i>Tbx1</i> Genetically Interacts With the Transforming Growth Factor-β/Bone Morphogenetic Protein Inhibitor <i>Smad7</i> During Great Vessel Remodeling
Authors: Irinna Papangeli, Peter J. Scambler
Journal: Circulation Research (2012)

Rationale: Growth and remodeling of the pharyngeal arch arteries are vital for the development of a mature great vessel system. Dysmorphogenesis of the fourth arch arteries can result in interruption of the aortic arch type B, typically found in DiGeorge syndrome. Tbx1 haploinsufficient embryos, which model DiGeorge syndrome, display fourth arch artery defects during formation of the vessels. Recovery from such defects is a documented yet unexplained phenotype in Tbx1 haploinsufficiency. Objective: To understand the nature of fourth arch artery growth recovery in Tbx1 haploinsufficiency and its underlying genetic control. Methods and Results: We categorized vessel phenotypes of Tbx1 heterozygotes as hypoplastic or aplastic at the conclusion of pharyngeal artery formation and compared these against the frequency of vessel defects scored at the end of great vessel development. The frequency of hypoplastic vessels decreased during embryogenesis, whereas no reduction of vessel aplasia was seen, implying recovery is attributable to remodeling of hypoplastic vessels. We showed that Smad7 , an inhibitory Smad within the transforming growth factor-β pathway, is regulated by Tbx1, is required for arch artery remodeling, and genetically interacts with Tbx1 in this process. Tbx1 and Tbx1 ; Smad7 haploinsufficiency affected several remodeling processes; however, concurrent haploinsufficiency particularly impacted on the earliest stage of vascular smooth muscle cell vessel coverage and subsequent fibronectin deposition. Conditional reconstitution of Smad7 with a Tbx1Cre driver indicated that the interaction between the 2 genes is cell autonomous. Conclusions: Tbx1 acts upstream of Smad7 controlling vascular smooth muscle and extracellular matrix investment of the fourth arch artery.
Treating Metastatic Solid Tumors With Bortezomib and a Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Receptor Agonist Antibody
Authors: A. Shanker, A. D. Brooks, C. A. Tristan, J. W. Wine, P. J. Elliott, H. Yagita, K. Takeda, M. J. Smyth, W. J. Murphy, T. J. Sayers
Journal: JNCI Journal of the National Cancer Institute (2008)

Resistance of tumors to cell death signals poses a complex clinical problem. We explored the therapeutic potential and in vivo toxicity of a combination of bortezomib, a proteasome inhibitor, and MD5-1, a tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (DR5) agonist monoclonal antibody, in mouse carcinomas. METHODS; Mice bearing Renca-FLAG (renal) or 4T1 (mammary) tumors were treated with bortezomib and/or MD5-1 and examined for lung metastases (Renca-FLAG: n = 93; 4T1: n = 40) or monitored for survival (Renca-FLAG: n = 143). Toxicity was assessed by histopathology and hematology. Viability and apoptotic signaling in Renca-FLAG and 4T1 cells treated with bortezomib alone or in combination with TRAIL were analyzed using 3-[4,5-dimethyiazol-2-yl-5]-[3-carboxymethyloxyphenyl]-2-[4-sulfophenyl]-2H tetrazolium assay and by measuring mitochondrial membrane depolarization and caspase-8 and caspase-3 activation. All statistical tests were two-sided.Bortezomib (20 nM) sensitized Renca-FLAG and 4T1 cells to TRAIL-mediated apoptosis (mean percent decrease in numbers of viable cells, bortezomib + TRAIL vs TRAIL: Renca-FLAG, 95% vs 34%, difference = 61%, 95% confidence interval [CI] = 52% to 69%, P < .001; 4T1, 85% vs 20%, difference = 65%, 95% CI = 62% to 69%, P < .001). Sensitization involved activation of caspase-8 and caspase-3 but not mitochondrial membrane depolarization, suggesting an amplified signaling of the extrinsic cell death pathway. Treatment with bortezomib and MD5-1 reduced lung metastases in mice carrying Renca and 4T1 tumors (mean number of metastases, bortezomib + MD5-1 vs MD5-1: Renca-FLAG, 1 vs 8, difference = 7, 95% CI = 5 to 9, P < .001; 4T1, 1 vs 12, difference = 11, 95% CI = 9 to 12, P < .001) and increased median survival of mice bearing Renca-FLAG tumors (bortezomib + MD5-1 vs bortezomib + control isotype antibody: 22 of 30 [73%] were still alive at day 180 vs median survival of 42 days [95% CI = 41 to 44 days, P < .001]) in the absence of obvious toxicity.Bortezomib combined with DR5 agonist monoclonal antibody may be a useful treatment for metastatic solid tumors.