tbuckley/cabot-search huggingface dataset:
Evidence for vitamin D deficiency and increased prevalence of fractures in autoimmune bullous skin diseases
Authors: A.V. Marzano, V. Trevisan, C. Eller-Vainicher, E. Cairoli, L. Marchese, V. Morelli, P. Beck-Peccoz, C. Crosti, I. Chiodini
Journal: British Journal of Dermatology (2012)

Vitamin D deficiency plays a role in autoimmune diseases and risk of fractures. No data are available on vitamin D levels and vertebral fractures in autoimmune bullous skin diseases.To assess serum vitamin D levels and the prevalence of vertebral fractures in patients with pemphigus vulgaris (PV) and bullous pemphigoid (BP), potentially fatal autoimmune bullous disorders.We studied 13 consecutive inpatients with untreated active PV (six men and seven women, mean ± SD age 53·5 ± 14·3 years), 15 with BP (seven men and eight women, mean ± SD age 76·9 ± 12·4 years) and 28 age-, body mass index- and sex-matched controls. The 25-hydroxyvitamin D (25-OHD) levels and presence of vertebral fractures on spinal X-ray were assessed in all subjects.In patients with PV, 25-OHD levels were lower (mean ± SD 12 ± 4·4 ng mL(-1) ) and prevalence of severe hypovitaminosis D higher (62%) than in controls (mean ± SD 22·2 ± 11·7 ng mL(-1) , P = 0·012; 23%, P = 0·0047, respectively). The prevalence of fractures was 54% and 31% in patients with PV and controls, respectively. Patients with BP showed lower 25-OHD levels (mean ± SD 9·6 ± 7·2 ng mL(-1) ) and higher prevalence of severe hypovitaminosis D (73%) than controls (mean ± SD 22·6 ± 18·7 ng mL(-1) , P = 0·022; 27%, P = 0·01, respectively). The prevalence of fractures tended to be higher in patients with BP than in controls (67% vs. 33%, respectively, P = 0·068).The low 25-OHD levels found in PV and BP may suggest a role for this agent in their pathogenesis. The increased prevalence of fractures should be taken into consideration in patients who must be given corticosteroids.
Interleukin-7-Dependent Expansion and Persistence of Melanoma-Specific T Cells in Lymphodepleted Mice Lead to Tumor Regression and Editing
Authors: Li-Xin Wang, Rui Li, Guojun Yang, May Lim, Aisling O'Hara, Yiwei Chu, Bernard A. Fox, Nicholas P. Restifo, Walter J. Urba, Hong-Ming Hu
Journal: Cancer Research (2005)

Abstract Active-specific immunotherapy with dendritic cells loaded with peptide derived from the melanoma antigen, gp100, failed to mediate regression of established B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and subsequent deletion of adoptively transferred naive CD8+ T-cell receptor transgenic (pmel-1) T cells specific for gp100 in normal mice. In lymphodepleted mice, dendritic cell vaccination produced greater T-cell expansion, long-term persistence of memory T cells, and tumor regression. Most tumors that persisted in the presence of functional memory T cells had either lost or exhibited reduced expression of MHC class I or gp100 proteins. In contrast to other naive T cells, pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster proliferation and a more differentiated phenotype after exposure to peptide-pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was highly dependent on interleukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7 was neutralized, two critical homeostatic cytokines produced in response to the irradiation-induced lymphodepletion.
EAU Guidelines on Renal Cell Carcinoma: 2014 Update
Authors: Borje Ljungberg, Karim Bensalah, Steven Canfield, Saeed Dabestani, Fabian Hofmann, Milan Hora, Markus A. Kuczyk, Thomas Lam, Lorenzo Marconi, Axel S. Merseburger, Peter Mulders, Thomas Powles, Michael Staehler, Alessandro Volpe, Axel Bex
Journal: European Urology (2015)
Mechanism of CO2 response in cerebral arteries of the newborn pig: role of phospholipase, cyclooxygenase, and lipoxygenase pathways.
Authors: L C Wagerle, O P Mishra
Journal: Circulation Research (1988)

The role of phospholipase, lipoxygenase, and cyclooxygenase pathways in the mechanism of the cerebrovascular response to CO2 and H+ was investigated in newborn piglets. Responsiveness of pial arterioles, 48-206 micron diameter, to inhalation of 6% CO2 and to suffusion of acidic cerebrospinal fluid (CSF, pH = 6.84), adenosine (10(-4) M), or theophylline (10(-2) M) was studied using a closed cranial window. Pial arteriolar diameter was measured using intravital microscopy. Phospholipase inhibitors quinacrine hydrochloride (10(-4) M in CSF) and p-bromophenacyl bromide (10(-4) M in CSF) abolished the CO2 vasodilation from delta diameter = 27 +/- 5% and 28 +/- 3% during baseline to 0 +/- 4% and -1 +/- 1% following the respective inhibitors. Following administration of the cyclooxygenase inhibitor indomethacin (5 mg/kg i.v.), the CO2 response was converted from vasodilation, 31 +/- 6%, to constriction, -4 +/- 1% (p less than 0.001), while the lipoxygenase inhibitor nordihydroguaiaretic acid (2 mg/kg i.v. or 10(-4) M in CSF) augmented the pial arteriolar response to CO2 from 21 +/- 4% to 34 +/- 7% (p less than 0.005). Topical application of superoxide dismutase (40 units/ml CSF) plus catalase (40 units/ml CSF) also appeared to augment the CO2 response. Suffusion of the cortical surface with acidic CSF at constant PCO2 increased pial arteriolar diameter by 11 +/- 2% that was also abolished by indomethacin. Vasodilatory responses to topical adenosine and theophylline were not affected by indomethacin, suggesting specificity for H+ ion-related vasodilation.(ABSTRACT TRUNCATED AT 250 WORDS)
HER2 in high-risk rectal cancer patients treated in EXPERT-C, a randomized phase II trial of neoadjuvant capecitabine and oxaliplatin (CAPOX) and chemoradiotherapy (CRT) with or without cetuximab
Authors: F. Sclafani, A. Roy, D. Cunningham, A. Wotherspoon, C. Peckitt, D. Gonzalez de Castro, J. Tabernero, B. Glimelius, A. Cervantes, Z. Eltahir, J. Oates, I. Chau
Journal: Annals of Oncology (2013)
Enhanced Protein Profiling Arrays with ELISA-Based Amplification for High-Throughput Molecular Changes of Tumor Patients’ Plasma
Authors: Ruochun Huang, Ying Lin, Qian Shi, Lisa Flowers, Sumathi Ramachandran, Ira R. Horowitz, Sampath Parthasarathy, Ruo-Pan Huang
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this study is to develop a high-throughput approach to detect protein expression from hundreds and thousands of samples and to apply this technology to profile circulating angiogenic factor protein levels in patients with gynecological tumors. Experimental Design: Analytes containing a mixture of protein are immobilized onto antibody-coated surface of support in array format. The presence of protein in analytes is detected with biotin-labeled antibody coupled with an enhanced chemiluminescence or fluorescence detection system. The exact amount of protein can be quantitatively measured. The expression levels of five angiogenic factors (angiogenin, interleukin 8, vascular endothelial growth factor, platelet-derived growth factor, and epidermal growth factor) from 157 samples were quantitatively measured using this novel protein array technology and were statistically analyzed. The expression patterns of angiogenic factors were analyzed using two-way hierarchical cluster analysis approach. Results: A novel protein array technology, which can simultaneously and quantitatively measure few protein levels from hundreds and thousands of samples was developed. Only minute amounts of sample are required for the assay. This approach also features high sensitivity and specificity. Using this novel protein array approach, we analyzed the plasma expression levels of five angiogenic factors in 137 patients diagnosed with a tumor and 20 controls. Statistical analysis reveals different expression levels of angiogenic factors between patients and controls. Cluster analysis suggests a possible classification of normal subjects from patients. Conclusions: Enhanced protein profiling arrays provide a high-throughput and sensitive system to detect one or few protein from hundreds and thousands of samples. Such an approach should have broad application in biomedical discovery.
Homeostatic MyD88-dependent signals cause lethal inflamMation in the absence of A20
Authors: Emre E. Turer, Rita M. Tavares, Erwan Mortier, Osamu Hitotsumatsu, Rommel Advincula, Bettina Lee, Nataliya Shifrin, Barbara A. Malynn, Averil Ma
Journal: The Journal of Experimental Medicine (2008)

Toll-like receptors (TLRs) on host cells are chronically engaged by microbial ligands during homeostatic conditions. These signals do not cause inflammatory immune responses in unperturbed mice, even though they drive innate and adaptive immune responses when combating microbial infections. A20 is a ubiquitin-modifying enzyme that restricts exogenous TLR-induced signals. We show that MyD88-dependent TLR signals drive the spontaneous T cell and myeloid cell activation, cachexia, and premature lethality seen in A20-deficient mice. We have used broad spectrum antibiotics to demonstrate that these constitutive TLR signals are driven by commensal intestinal flora. A20 restricts TLR signals by restricting ubiquitylation of the E3 ligase tumor necrosis factor receptor–associated factor 6. These results reveal both the severe proinflammatory pathophysiology that can arise from homeostatic TLR signals as well as the critical role of A20 in restricting these signals in vivo. In addition, A20 restricts MyD88-independent TLR signals by inhibiting Toll/interleukin 1 receptor domain–containing adaptor inducing interferon (IFN) β–dependent nuclear factor κB signals but not IFN response factor 3 signaling. These findings provide novel insights into how physiological TLR signals are regulated.
Nitric Oxide Modulates Myocardial Oxygen Consumption in the Failing Heart
Authors: YingJie Chen, Jay H. Traverse, Ruisheng Du, MingXiao Hou, Robert J. Bache
Journal: Circulation (2002)

Endogenous nitric oxide (NO) has been reported to inhibit oxygen consumption in the normal heart, so that nonselective inhibition of NO synthase (NOS) caused an increase of myocardial oxygen consumption (MVO2). Although endothelial NOS responses are depressed in congestive heart failure (CHF), inducible NOS (iNOS) may be expressed in failing myocardium.This study tested the hypothesis that NOS inhibition would increase MVO2 in the failing heart. CHF was produced in dogs by use of the rapid ventricular pacing model. In comparison with normal values, animals with CHF had reduced coronary blood flow and MVO2 at rest, with a blunted response to treadmill exercise. Selective iNOS inhibition with S-methylisothiourea (1.5 mg/kg IC) increased left ventricular systolic pressure and left ventricular dP/dt and caused an increase in MVO2 at rest and during exercise (P<0.05), with a parallel upward shift in the relationship between MVO2 and rate-pressure product. In contrast, S-methylisothiourea had no effect on MVO2 or coronary flow in normal animals, although nonselective NOS inhibition with N(G)-nitro-L-arginine did cause an increase of MVO2 in normal and in CHF animals.The results indicate that endogenous NO can modulate MVO2 in failing hearts, but unlike the normal heart, this NO appears to be produced, at least in part, by iNOS.
Successful T cell priming in B cell-deficient mice.
Authors: M M Epstein, F Di Rosa, D Jankovic, A Sher, P Matzinger
Journal: The Journal of Experimental Medicine (1995)

B cells are an abundant population of lymphocytes that can efficiently capture, process, and present antigen for recognition by activated or memory T cells. Controversial experiments and arguments exist, however, as to whether B cells are or should be involved in the priming of virgin T cells in vivo. Using B cell-deficient mice, we have studied the role of B cells as antigen-presenting cells in a wide variety of tests, including assays of T cell proliferation and cytokine production in responses to protein antigens, T cell killing to minor and major histocompatibility antigens, skin graft rejection, and the in vitro and in vivo responses to shistosome eggs. We found that B cells are not critical for either CD4 or CD8 T cell priming in any of these systems. This finding lends support to the notion that the priming of T cells is reserved for specialized cells such as dendritic cells and that antigen presentation by B cells serves distinct immunological functions.
LSC 2013 abstract - Expression patterns and putative roles of forkhead box F1 in normal lung and idiopathic pulmonary fibrosis
Authors: Laurent Plantier, Sara Melboucy-Belkhir, Pauline Pradere, Stephanie Brayer, Guy Leseche, Bruno Crestani
Journal: European Respiratory Journal (2013)

Introduction:  Forkhead Box F1 (FOXF1 ) is an ontogenic transcription factor expressed in fetal lung mesenchyme. We hypothesised that altered FOXF1 expression may contribute to the profibrotic phenotype of lung fibroblasts in Idiopathic Pulmonary Fibrosis (IPF).   Methods:  FOXF1 expression was determined in normal (n=8) and IPF (n=17) lung biopsies. FOXF1 expression was induced or repressed in human normal (n=6) and IPF (n=6) lung fibroblasts by transfection of plasmids, siRNAs or lentiviral vectors. Proliferation, migration, collagen-1 (COL1) synthesis and gene expression were determined.   Results:  In normal lungs, FOXF1 was detected in smooth muscle, endothelium, and 42% of alveolar septal cells. Confocal microscopy of alveolar septa showed FOXF1 restricted to cells lacking epithelial (cytokeratin) and leucocyte (CD45) markers; 80% of FOXF1+ cells expressed CD31, an endothelial marker. A similar pattern was observed in normal regions of IPF lungs, whereas fibroblastic foci often lacked FOXF1;  FOXF1  mRNA was lower in IPF lung homogenate compared to normal lungs. In normal fibroblasts, FOXF1 knockdown induced proliferation and COL1 expression; FOXF1 expression induced migration and repressed COL1. mRNA microarrays identified  ARPC2  as a putative FOXF1 target. In IPF fibroblasts, FOXF1 knockdown and expression repressed and induced migration.   Conclusion:  In adult lung, FOXF1 was expressed in cell types consistent with mesenchymal specificity. In normal fibroblasts, FOXF1 acted as a tumor suppressor and regulated migration and COL1 expression. In IPF, reduced FOXF1 levels may confer cells of fibroblastic foci a trophic advantage and derepress collagen synthesis.
Homogeneously Staining Regions and Double Minutes in a Human Cell Line: Chromatin Organization and DNA Content&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: G Bahr, F Gilbert, G Balaban, W Engler
Journal: JNCI Journal of the National Cancer Institute (1983)

Homogeneously staining regions (HSR) and double minutes, two novel chromosome abnormalities, are believed to represent sites of gene amplification. The basic organization of chromatin in an HSR in a human neuroblastoma cell line was shown, by electron microscopy, to be similar to that in a normal chromosome. Double minutes from another human neuroblastoma cell line were found, by dry mass determination, to contain an average of 1.41 X 10(-14) g DNA. This quantity corresponds to 6.38 X 10(3) kilobase DNA per double minute.
Dichotomy effects of Akt signaling in breast cancer
Authors: Zhengang Peng, Jennifer Chao Weber, Zhaosheng Han, Rulong Shen, Wenchao Zhou, James R Scott, Michael WY Chan, Huey-Jen L Lin
Journal: Molecular Cancer (2012)

Abstract Background The oncogenic roles contributed by the Akt/PKB kinase family remain controversial and presumably depend on cell context, but are perceived to be modulated by an interplay and net balance between various isoforms. This study is intended to decipher whether distinct Akt kinase isoforms exert either redundant or unique functions in regulating neoplastic features of breast cancer cells, including epithelial-mesenchymal transition (EMT), cell motility, and stem/progenitor cell expansion. Results We demonstrate that overactivation of Akt signaling in nonmalignant MCF10A cells and in primary cultures of normal human mammary epithelial tissue results in previously unreported inhibitory effects on EMT, cell motility and stem/progenitor cell expansion. Importantly, this effect is largely redundant and independent of Akt isoform types. However, using a series of isogenic cell lines derived from MCF-10A cells but exhibiting varying stages of progressive tumorigenesis, we observe that this inhibition of neoplastic behavior can be reversed in epithelial cells that have advanced to a highly malignant state. In contrast to the tumor suppressive properties of Akt, activated Akt signaling in MCF10A cells can rescue cell viability upon treatment with cytotoxic agents. This feature is regarded as tumor-promoting. Conclusion We demonstrate that Akt signaling conveys novel dichotomy effects in which its oncogenic properties contributes mainly to sustaining cell viability, as opposed to the its tumor suppressing effects, which are mediated by repressing EMT, cell motility, and stem/progenitor cell expansion. While the former exerts a tumor-enhancing effect, the latter merely acts as a safeguard by restraining epithelial cells at the primary sites until metastatic spread can be moved forward, a process that is presumably dictated by the permissive tumor microenvironment or additional oncogenic insults.
Route of Administration Modulates the Induction of Dendritic Cell Vaccine–Induced Antigen-Specific T Cells in Advanced Melanoma Patients
Authors: W. Joost Lesterhuis, I. Jolanda M. de Vries, Gerty Schreibelt, Annechien J.A. Lambeck, Erik H.J.G. Aarntzen, Joannes F.M. Jacobs, Nicole M. Scharenborg, Mandy W.M.M. van de Rakt, Annemiek J. de Boer, Sandra Croockewit, Michelle M. van Rossum, Roel Mus, Wim J.G. Oyen, Otto C. Boerman, Sophie Lucas, Gosse J. Adema, Cornelis J.A. Punt, Carl G. Figdor
Journal: Clinical Cancer Research (2011)

It is unknown whether the route of administration influences dendritic cell (DC)-based immunotherapy. We compared the effect of intradermal versus intranodal administration of a DC vaccine on induction of immunologic responses in melanoma patients and examined whether concomitant administration of interleukin (IL)-2 increases the efficacy of the DC vaccine.HLA-A2.1(+) melanoma patients scheduled for regional lymph node dissection were vaccinated four times biweekly via intradermal or intranodal injection with 12 × 10⁶ to 17 × 10⁶ mature DCs loaded with tyrosinase and gp100 peptides together with keyhole limpet hemocyanin (KLH). Half of the patients also received low-dose IL-2 (9 MIU daily for 7 days starting 3 days after each vaccination). KLH-specific B- and T-cell responses were monitored in blood. gp100- and tyrosinase-specific T-cell responses were monitored in blood by tetramer analysis and in biopsies from delayed-type hypersensitivity (DTH) skin tests by tetramer and functional analyses with (51)Cr release assays or IFNγ release, following coculture with peptide-pulsed T2 cells or gp100- or tyrosinase-expressing tumor cells.In 19 of 43 vaccinated patients, functional tumor antigen-specific T cells could be detected. Although significantly more DCs migrated to adjacent lymph nodes upon intranodal vaccination, this was also highly variable with a complete absence of migration in 7 of 24 intranodally vaccinated patients. Intradermal vaccinations proved superior in inducing functional tumor antigen-specific T cells. Coadministration of IL-2 did not further augment the antigen-specific T-cell response but did result in higher regulatory T-cell frequencies.Intradermal vaccination resulted in superior antitumor T-cell induction when compared with intranodal vaccination. No advantage of additional IL-2 treatment could be shown.
P300 Latency in Geriatric Depression
Authors: B Kalayam, G S Alexopoulos, S Kindermann, T Kakuma, G G Brown, R C Young
Journal: American Journal of Psychiatry (1998)

OBJECTIVE: The purpose of this study was to determine if P300 latency is prolonged in geri~atric depression and if longer P300 latency and deficits in initiation and errors of perseveration in depressed elderly patients are related to risk factors for vascular disease. METHOD: Geriatric patients with unipolar depression (N=43) and elderly comparison subjects (N=24) were assessed for depressive symptoms, cognitive functions, risk factors for vascular disease, and P300 latency. RESULTS: Depressed elderly patients had longer P300 latency than normal elderly subjects. In the depressed patients, P300 latency was related to deficits in initiation and errors in perseveration. Risk factors for vascular disease were associated not only with P300 latency but also with deficits in initiation and errors in perseveration. CONCLUSIONS: Functional impairment of the cortico-striato-pallido-thalamo-cortical pathways from vascular disease, implicated in late-life depressive disorders, may explain not only deficits in initiation and errors in perseveration but also longer P300 latency in depressed elderly patients. These results are preliminary and need further examination with brain imaging and more sensitive neuropsychological measures.
Interleukin-1 receptor antagonist and interleukin-6 for early diagnosis of neonatal sepsis 2 days before clinical manifestation
Authors: Helmut Küster, Michael Weiss, Andreas E Willeitner, Stefanie Detlefsen, Irmela Jeremias, Juraj Zbojan, Ralf Geiger, Gert Lipowsky, Georg Simbruner
Journal: The Lancet (1998)
In cutaneous T-cell lymphoma, class II MHC molecules on CD1+ antigen-presenting cells are upregulated in involved compared with uninvolved epidermis
Authors: E.R. HANSEN, B. BANG, J.K. LARSEN, G.L. VEJLSGAARD, O. BAADSGAARD
Journal: British Journal of Dermatology (1994)

Journal Article In cutaneous T‐cell lymphoma, class II MHC molecules on CD1+ antigen‐presenting cells are upregulated in involved compared with uninvolved epidermis Get access E.R. HANSEN, E.R. HANSEN Departments of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark Erik Rene Hansen, MD, Department of Dermatology, Gentofte Hospital, University of Copenhagen, Niels Andersens Vej 65, 2900 Hellerup, Denmark. Search for other works by this author on: Oxford Academic Google Scholar B. BANG, B. BANG Departments of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar J.K. LARSEN, J.K. LARSEN Finsen Laboratory, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar G.L. VEJLSGAARD, G.L. VEJLSGAARD Rigshospitalet, University of Copenhagen, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar O. BAADSGAARD O. BAADSGAARD Departments of Dermatology, Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 131, Issue 6, 1 December 1994, Pages 780–788, https://doi.org/10.1111/j.1365-2133.1994.tb08579.x Published: 01 December 1994 Article history Accepted: 12 April 1994 Published: 01 December 1994