tbuckley/cabot-search huggingface dataset:
Anti–Interleukin 10 Receptor Monoclonal Antibody Is an Adjuvant for T Helper Cell Type 1 Responses to Soluble Antigen Only in the Presence of Lipopolysaccharide
Authors: Antonio G. Castro, Margaret Neighbors, Stephen D. Hurst, Francesca Zonin, Regina A. Silva, Erin Murphy, Yong-Jun Liu, Anne O'Garra
Journal: The Journal of Experimental Medicine (2000)

Soluble foreign antigen usually leads to a transient clonal expansion of antigen-specific T cells followed by the deletion and/or functional inactivation of the cells. As interleukin (IL)-10 is a key immunoregulatory cytokine, we questioned whether neutralization of IL-10 during priming with soluble antigen could prime for a subsequent T helper cell type 1 (Th1) effector recall response. By using an adoptive transfer model to track the fate of antigen-specific T cell receptor (TCR)-transgenic CD4(+) T cells, we show that administration of soluble ovalbumin (OVA) protein, but not OVA(323-339) peptide antigen, together with an anti-IL-10 receptor (R) mAb led to the enhancement of a Th1 response upon rechallenge. Lipopolysaccharide (LPS) present in the protein was necessary for priming for Th1 recall responses in the presence of anti-IL-10R mAb, as removal of LPS abrogated this effect. Moreover, addition of LPS to the peptide did not itself allow priming for recall Th1 effector responses unless endogenous levels of IL-10 were neutralized with an anti-IL-10R mAb. A significant increase in OVA-specific IgG1 and IgG2a isotypes was observed when the protein antigen was administered with anti-IL-10R mAb; however, this was not the case with peptide antigen administered together with anti-IL-10R and LPS. Our data, showing that LPS receptor signaling and neutralization of endogenous immunosuppressive cytokines is essential for Th1 priming, has important implications for the design of relevant vaccines for effective in vivo immunotherapy.
Peptide-Loaded Langerhans Cells, Despite Increased IL15 Secretion and T-Cell Activation<i>In Vitro</i>, Elicit Antitumor T-Cell Responses Comparable to Peptide-Loaded Monocyte-Derived Dendritic Cells<i>In Vivo</i>
Authors: Emanuela Romano, Marco Rossi, Gudrun Ratzinger, Maria-Angeles de Cos, David J. Chung, Katherine S. Panageas, Jedd D. Wolchock, Alan N. Houghton, Paul B. Chapman, Glenn Heller, Jianda Yuan, James W. Young
Journal: Clinical Cancer Research (2011)

We compared the efficacy of human Langerhans cells (LC) as tumor immunogens in vivo with monocyte-derived dendritic cells (moDC) and investigated how interleukin 15 (IL15) supports optimal DC-stimulated antitumor immunity.American Joint Committee on Cancer stage III/IV melanoma patients participated in this first clinical trial comparing melanoma peptide-pulsed LC with moDC vaccines (NCT00700167, www.ClinicalTrials.gov). Correlative studies evaluated mechanisms mediating IL15 support of DC-stimulated antitumor immunity.Both DC vaccines were safe and immunogenic for melanoma antigens. LC-based vaccines stimulated significantly greater tyrosinase-HLA-A*0201 tetramer reactivity than the moDC-based vaccines. The two DC subtypes were otherwise statistically comparable, in contrast to extensive prior data in vitro showing LC superiority. LCs synthesize much more IL15 than moDCs and stimulate significantly more antigen-specific lymphocytes with a cytolytic IFN-γ profile even without exogenous IL15. When supplemented by low-dose IL15, instead of IL2, moDCs stimulate 5 to 6 logs more tumor antigen-specific effector memory T cells (T(EMRA)) over 3 to 4 weeks in vitro. IL2 and IL15 can be synergistic in moDC stimulation of cytolytic T cells. IL15 promotes T-cell expression of the antiapoptotic bcl-2 and inhibits candidate regulatory T-cell (Treg) expansion after DC stimulation, countering two effects of IL2 that do not foster tumor immunity.MoDC-based vaccines will require exogenous IL15 to achieve clinical efficacy. Alternatively, LCs can couple the endogenous production of IL15 with potent T-cell stimulatory activity. Optimization of full-length tumor antigen expression for processing into multiple immunogenic peptides for presentation by both class I and II MHC therefore merits emphasis to support more effective antitumor immunity stimulated by LCs.
Posterior Mediastinal Mass
Authors: S. Amjad Hussain
Journal: JAMA (1976)

<h3>Common</h3> Neurogenic neoplasms Arising from peripheral nerves Neurofibroma Neurilemoma or schwannoma (benign or malignant) Arising from sympathetic ganglia Ganglioneuroma (benign) Neuroblastoma } malignant Sympathicoblastoma Arising from paraganglionic cells Pheochromocytoma Paraganglioma } benign or malignant or chemodectoma Parasitic cysts (hydatid) Meningocele (meningomyelocele) Neurenteric (archenteric) cyst Gastroenteric cyst Thoracic duct cyst Primary esophageal lesions Neoplasm Esophageal diverticula Megaesophagus Esophageal hiatus hernia Hernia through the foramen of Bochdalek Diseases of thoracic spine Neoplasms Infectious spondylitis Tuberculous Nontuberculous Extramedullary hematopoiesis Aortic aneurysm <h3>Diagnosis</h3> Tuberculous spondylitis. <h3>Comment</h3> A 45-year-old woman was referred to the Lady Reading Hospital, Peshawar, Pakistan, in October 1972 for evaluation of an abnormal chest roentgenogram (Fig 1). The film was taken because of vague chest pains. A Casoni test for hydatid disease was negative. Results of a physical examination showed no abnormalities except for some tenderness in the midthoracic spine. There was no deformity of the spine nor of the
Three-Dimensional Black-Blood Cardiac Magnetic Resonance Coronary Vessel Wall Imaging Detects Positive Arterial Remodeling in Patients With Nonsignificant Coronary Artery Disease
Authors: W. Yong Kim, Matthias Stuber, Peter Börnert, Kraig V. Kissinger, Warren J. Manning, René M. Botnar
Journal: Circulation (2002)

Background — Direct noninvasive visualization of the coronary vessel wall may enhance risk stratification by quantifying subclinical coronary atherosclerotic plaque burden. We sought to evaluate high-resolution black-blood 3D cardiovascular magnetic resonance (CMR) imaging for in vivo visualization of the proximal coronary artery vessel wall. Methods and Results — Twelve adult subjects, including 6 clinically healthy subjects and 6 patients with nonsignificant coronary artery disease (10% to 50% x-ray angiographic diameter reduction) were studied with the use of a commercial 1.5 Tesla CMR scanner. Free-breathing 3D coronary vessel wall imaging was performed along the major axis of the right coronary artery with isotropic spatial resolution (1.0×1.0×1.0 mm 3 ) with the use of a black-blood spiral image acquisition. The proximal vessel wall thickness and luminal diameter were objectively determined with an automated edge detection tool. The 3D CMR vessel wall scans allowed for visualization of the contiguous proximal right coronary artery in all subjects. Both mean vessel wall thickness (1.7±0.3 versus 1.0±0.2 mm) and wall area (25.4±6.9 versus 11.5±5.2 mm 2 ) were significantly increased in the patients compared with the healthy subjects (both P &lt;0.01). The lumen diameter (3.6±0.7 versus 3.4±0.5 mm, P =0.47) and lumen area (8.9±3.4 versus 7.9±3.5 mm 2 , P =0.47) were similar in both groups. Conclusions — Free-breathing 3D black-blood coronary CMR with isotropic resolution identified an increased coronary vessel wall thickness with preservation of lumen size in patients with nonsignificant coronary artery disease, consistent with a “Glagov-type” outward arterial remodeling. This novel approach has the potential to quantify subclinical disease.
PWE-015 Biomarkers For Early Detection Of Colorectal Cancer And Polyps: Systematic Review
Authors: R Shah, E Jones, V Vidart, P Kuppen, J Conti, N Francis
Journal: Gut (2014)

<h3>Introduction</h3> Early detection of colorectal cancer plays an important role in patient survival. A screening program for colorectal cancer has been proven to reduce mortality from the disease. There is a growing interest in potential biomarkers to predict early colorectal cancer as current screening modalities lack compliance and specificity. The aim of this study was to systematically review the recent literature to identify all published biomarkers for early detection of colorectal cancer and polyps; to summarise performance characteristics of each biomarker and to test if they can be used for designing new screening tests for colorectal cancer. <h3>Methods</h3> Literature searches were conducted according to PRISMA guidelines, of Medline, EMBASE and PubMed databases for relevant papers since the most recent systematic review in 2007. The review focused on human studies reporting on early detection of colorectal cancer and/or colorectal polyps using biomarkers. The studies were categorised into faecal, blood or tissue biomarkers and these were then subdivided depending on the category of marker being examined: (1) DNA biomarkers, (2) RNA biomarkers, (3) Protein biomarkers or (4) Other. Our review reported on the sensitivity and specificity of each biomarker, alongside their 95% confidence interval ranges. These values were used in conjunction with disease prevalence to obtain positive and negative predictive values. <h3>Results</h3> The search strategy identified 3348 abstracts. 44 papers, describing a total of 9908 participants and examining 67 different tumour markers were included in this review for data extraction and analysis. Overall sensitivities for colorectal cancer detection by faecal DNA markers ranged from 53% to 87% with varying specificities, however, all above 76%. Combining DNA markers increased the sensitivity of colorectal cancer detection to 86%. A 6-gene faecal DNA panel obtained a sensitivity of 68% for adenoma detection with a high specificity of 90%. Canine scent detection of volatile organic compounds had a sensitivity of detecting colorectal cancer of 99% and specificity of 97% on a study of nearly 300 patients. A panel of serum DNA and/or RNA biomarkers provide a sensitivity and specificity above 85% for all stages of colorectal cancer. A serum 4-gene DNA panel of markers has an increased specificity of 91% for adenoma detection. <h3>Conclusion</h3> This review has demonstrated that there are several evolving faecal and serum biomarkers that can predict colorectal cancer. When combined into biomarker panels, higher sensitivity and specificities for early detection of colorectal cancer and adenomas are achieved. Further research is required to validate these markers in a well-structured population based study. <h3>Disclosure of Interest</h3> None Declared.
Reversal of Cimetidine-Induced Stupor by Physostigmine
Authors: Joseph P. Fiore
Journal: JAMA (1979)

<h3>To the Editor.—</h3> In a recent article by Mogelnicki and associates (241:826, 1979) regarding the use of physostigmine in two patients to reverse a stupor that was apparently induced by the histamine H<sub>2</sub>antagonist cimetidine, the authors note two possible explanations for the observed events: First, physostigmine was acting specifically to reverse an anticholinergic stupor caused by cimetidine. Cimetidine would be classified with a wide variety of other drugs known to produce the central anticholinergic syndrome, which is manifested by stupor in severe cases. If physostigmine was reversing a central anticholinergic stupor produced by cimetidine, presumably at H<sub>2</sub>receptors in the CNS, the clinical manifestations of the anticholinergic syndrome in these two patients were unusual because the patients did not first manifest the usual initial mental changes associated with the central anticholinergic syndrome, such as delirium and agitation, before their conditions progressed to stupor. The second explanation of
The Human <i>TLR</i> Innate Immune Gene Family Is Differentially Influenced by DNA Stress and <i>p53</i> Status in Cancer Cells
Authors: Maria Shatz, Daniel Menendez, Michael A. Resnick
Journal: Cancer Research (2012)

Abstract The transcription factor p53 regulates genes associated with a wide range of functions, including the Toll-like receptor (TLR) set of innate immunity genes, suggesting that p53 also modulates the human immune response. The TLR family comprises membrane glycoproteins that recognize pathogen-associated molecular patterns (PAMP) and mediate innate immune responses, and TLR agonists are being used as adjuvants in cancer treatments. Here, we show that doxorubicin, 5-fluorouracil, and UV and ionizing radiation elicit changes in TLR expression that are cell line- and damage-specific. Specifically, treatment-induced expression changes led to increased downstream cytokine expression in response to ligand stimulation. The effect of DNA stressors on TLR expression was mainly mediated by p53, and several p53 cancer-associated mutants dramatically altered the pattern of TLR gene expression. In all cell lines tested, TLR3 induction was p53-dependent, whereas induction of TLR9, the most stress-responsive family member, was less dependent on status of p53. In addition, each of the 10 members of the innate immune TLR gene family tested was differentially inducible. Our findings therefore show that the matrix of p53 status, chromosome stress, and responsiveness of individual TLRs should be considered in TLR-based cancer therapies. Cancer Res; 72(16); 3948–57. ©2012 AACR.
Identification of an RP1 Prevalent Founder Mutation and Related Phenotype in Spanish Patients with Early-Onset Autosomal Recessive Retinitis
Authors: Almudena Avila-Fernandez, Marta Corton, Koji M. Nishiguchi, Nelida Muñoz-Sanz, Belen Benavides-Mori, Fiona Blanco-Kelly, Rosa Riveiro-Alvarez, Blanca Garcia-Sandoval, Carlo Rivolta, Carmen Ayuso
Journal: Ophthalmology (2012)
PUVA-treatment of urticaria pigmentosa
Authors: Enno Christophers, Herbert Honigsmann, Klaus Wolff, Andrzej Langner
Journal: British Journal of Dermatology (1978)

Journal Article PUVA‐treatment of urticaria pigmentosa Get access Enno Christophers, Enno Christophers Department of Dermatology, University of Kiel, Germany Search for other works by this author on: Oxford Academic Google Scholar Herbert Hönigsmann, Herbert Hönigsmann Department of Dermatology, University of Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar Klaus Wolff, Klaus Wolff Department of Dermatology, University of Innsbruck, Austria Search for other works by this author on: Oxford Academic Google Scholar Andrzej Langner Andrzej Langner Department of Dermatology, University of Warsaw, Poland Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 98, Issue 6, 1 June 1978, Pages 701–702, https://doi.org/10.1111/j.1365-2133.1978.tb03592.x Published: 01 June 1978
Nitric Oxide Bioavailability and Its Potential Relevance to the Variation in Susceptibility to the Renal and Vascular Complications in Patients With Type 2 Diabetes
Authors: Kenneth A. Earle, Diane Harry, Mitra Madhavi, Karima Zitouni, Jeffrey Barron
Journal: Diabetes Care (2008)

OBJECTIVE—We compared the renal and systemic vascular (renovascular) response to a reduction of bioavailable nitric oxide (NO) in type 2 diabetic patients without nephropathy and of African and Caucasian heritage. RESEARCH DESIGN AND METHODS—Under euglycemic conditions, renal blood flow was determined by a constant infusion of paraminohippurate and changes in blood pressure and renal vascular resistance estimated before and after an infusion of l-Ng-monomethyl-l-arginine. RESULTS—In the African-heritage group, there was a significant fall in renal blood flow (Δ−46.0 ml/min per 1.73 m2; P &amp;lt; 0.05) and rise in systolic blood pressure (Δ10.0 mmHg [95% CI 2.3–17.9]; P = 0.017), which correlated with an increase in renal vascular resistance (r2 = 0.77; P = 0.004). CONCLUSIONS—The renal vasoconstrictive response associated with NO synthase inhibition in this study may be of relevance to the observed vulnerability to renal injury in patients of African heritage.
DISTRIBUTION OF SPIROCHÆTA ICTEROHÆMORRHAGIÆ IN THE ORGANS AFTER INTRAVENOUS SERUM TREATMENT
Authors: Renjiro Kaneko, Kikuzo Okuda
Journal: The Journal of Experimental Medicine (1918)

On the basis of these findings we believe that we are Justified in saying that the immune serum of Weil's disease is capable of destroying the spirochetes found within the organs in man, with the exception of the kidneys, and that the action of the serum upon the spirochetes is spirochetolytic and spirocheticidal. The scattered spirochetes in the kidney, on the other hand, are resistant to the action of the immune serum. The spirochetes disappear almost completely from the organs during the convalescent stage of Well's disease, even when no serum has been administered. The only organ to be excepted is again the kidney, but no comparison between .serum-treated and non-serum-treated cases should be made in this respect, for spirochetes are found numerously in the kidneys even with serum treatment. The disappearance of the spirochetes from the organs and tissues in Well's disease seems to be not so marked with the subcutaneous serum treatment as with the intravenous method, but the manner of their disappearance is about the same.
Immunohistochemical studies on proteoglycan expression in normal skin and chronic ulcers
Authors: K. Lundqvist, A. Schmidtchen
Journal: British Journal of Dermatology (2001)

Background Proteoglycans (PGs) represent a large family of complex molecules. They are found either as integral membrane components or constituents of the extracellular matrix. Their protein backbones are linked to different glycosaminoglycans, such as dermatan-, chondroitin-, keratan- or heparan sulphate. The molecules have specific functions during developmental processes as well as in diseases, such as cancer and inflammation. Objectives The expression patterns of various cell-associated heparan and chondroitin/dermatan-sulphate PGs in human skin and chronic venous ulcers were investigated. Methods Tissue sections from 11 patients with chronic venous ulcers were used in this study. Monoclonal antibodies were used for detection of the proteoglycans syndecan-1, -2 and -4, glypican, CD44 and perlecan. Results The different PGs exhibited individual staining patterns. Syndecan-1 and -4 and glypican expression in chronic ulcers differed from the staining in normal skin. Whereas the expression of syndecan-4 and glypican in intact skin was mostly in the pericellular regions of keratinocytes, the epidermal cells from the wound edge contained mostly intracellular PGs. In the wound edge, syndecan-4 was predominantly expressed by epidermal basal layer cells. Syndecan-1 was less expressed at the epidermal wound margins. PGs bind growth factors, regulate proteolytic activity and act as matrix receptors. Conclusions The altered expression patterns of glypican and syndecan-1 and -4 in chronic ulcers reflect their possible roles during inflammation and cell proliferation. Hence, analysis of PG expression should be of interest in future studies on normal as well as defective wound healing.
Control of Cardiac Growth by Histone Acetylation/Deacetylation
Authors: Johannes Backs, Eric N. Olson
Journal: Circulation Research (2006)

Histones control gene expression by modulating the structure of chromatin and the accessibility of regulatory DNA sequences to transcriptional activators and repressors. Posttranslational modifications of histones have been proposed to establish a "code" that determines patterns of cellular gene expression. Acetylation of histones by histone acetyltransferases stimulates gene expression by relaxing chromatin structure, allowing access of transcription factors to DNA, whereas deacetylation of histones by histone deacetylases promotes chromatin condensation and transcriptional repression. Recent studies demonstrate histone acetylation/deacetylation to be a nodal point for the control of cardiac growth and gene expression in response to acute and chronic stress stimuli. These findings suggest novel strategies for "transcriptional therapies" to control cardiac gene expression and function. Manipulation of histone modifying enzymes and the signaling pathways that impinge on them in the settings of pathological cardiac growth, remodeling, and heart failure represents an auspicious therapeutic approach.
Identification of novel CTL epitopes of CMV-pp65 presented by a variety of HLA alleles
Authors: Eisei Kondo, Yoshiki Akatsuka, Kiyotaka Kuzushima, Kunio Tsujimura, Shoji Asakura, Kohei Tajima, Yoshitoyo Kagami, Yoshihisa Kodera, Mitsune Tanimoto, Yasuo Morishima, Toshitada Takahashi
Journal: Blood (2003)
Immunoglobulin and complement deposition in skin of rheumatoid arthritis and systemic lupus erythematosus patients.
Authors: A.L Schroeter, D.L Conn, R.E Jordon
Journal: Annals of the Rheumatic Diseases (1976)

Rheumatoid arthritis (RA) was differentiated from systemic lupus erythematosus (SLE) by direct immunofluorescent techniques on skin specimens, using monospecific antisera for IgG, IgM, C3, C1q, properdin, and fibrin. Of 30 patients with RA studied, 20 had dermal vessel deposits of immunoglobulins and complement components in unaffected skin without the characteristic dermal-epidermal junctional fluorescence of SLE. Of 24 SLE patients studied, 24 had granular deposits of immunoglobulins and complement components in unaffected skin at the dermal-epidermal junction.
The Influence of Adiponectin Gene Polymorphism on the Rosiglitazone Response in Patients With Type 2 Diabetes
Authors: Eun Seok Kang, So Young Park, Hyeong Jin Kim, Chul Woo Ahn, Moonsuk Nam, Bong Soo Cha, Sung Kil Lim, Kyung Rae Kim, Hyun Chul Lee
Journal: Diabetes Care (2005)

OBJECTIVE —The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms. RESEARCH DESIGN AND METHODS —A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined. RESULTS —Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA1c value in the carriers of the GG genotype than in the carriers of the other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P = 0.001). In the haplotype analysis, the reductions in the FPG and HbA1c levels were smaller for the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P = 0.003). CONCLUSIONS —These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients.
A major costimulatory molecule on antigen-presenting cells, CTLA4 ligand A, is distinct from B7.
Authors: Y Wu, Y Guo, Y Liu
Journal: The Journal of Experimental Medicine (1993)

CTLA4 ligands are important costimulatory molecules because soluble CTLA4Ig blocks the induction of T cell responses and induces T cell tolerance. As CTLA4 immunoglobulin (CTLA4Ig) binds B7 when the latter is expressed on fibroblasts, it was widely assumed that CTLA4Ig blocks T cell costimulation by blocking the function of B7. Here we show that the major costimulatory ligand bound by CTLA4Ig (which we term CTLA4 ligand A) on antigen-presenting cells are not encoded by the B7 gene. CTLA4 ligand A also differs from B7 in cellular distribution and in the respective levels of expression. Both B7 and CTLA4 ligand A are critically involved in T cell costimulation.