tbuckley/cabot-search huggingface dataset:
Inhibition of Melanoma Growth by Targeting of Antigen to Dendritic Cells via an Anti-DEC-205 Single-Chain Fragment Variable Molecule
Authors: Theron S. Johnson, Karsten Mahnke, Volker Storn, Kurt Schönfeld, Sabine Ring, Dirk M. Nettelbeck, Hidde J. Haisma, Fabrice Le Gall, Roland E. Kontermann, Alexander H. Enk
Journal: Clinical Cancer Research (2008)

Abstract Purpose: Our goal was to target melanoma antigens to the dendritic cell-specific receptor DEC-205. DEC-205 is an antigen receptor expressed on dendritic cells and has been shown to guide antigens to MHC class I and II compartments for processing and presentation to T cells. Experimental Design: The melanoma tumor-associated antigen (TAA), gp100, was fused to the single-chain fragment variable (scFv) specific for DEC-205. The binding capacity of the scFv was tested on lymph node-isolated CD11c+ cells. Mixed lymphocyte reactions were carried out to show an increased proliferative capacity of gp100 antigen-specific CD4 and CD8 T cells. Furthermore the scFv-TAA was used in a therapeutic setting using two different melanoma mouse models. Results: C57Bl/6 mice were injected with scFv-DEC-205-gp100, monoclonal antibody anti-DEC-205, or PBS. Using fluorescence-activated cell sorting, we showed that lymph node CD11c+ dendritic cells stained positive for the binding of the scFv-mDEC-205-gp100 and the anti-DEC-205 monoclonal antibody, whereas the PBS-injected animals were negative. In mixed lymphocyte reactions, bone marrow-derived dendritic cells pulsed with scFv-mDEC-205-gp100 significantly increased proliferation of gp100-specific CD8+ and CD4+ T cells beyond gp100 peptide-pulsed or nonpulsed bone marrow-derived dendritic cells. Finally, in B16/F10 and RET models, a concentration-dependent suppression of tumor growth using scFv-mDEC-205-gp100 (66% reduction of tumor volume), in comparison with gp100 peptide vaccination, was observed. Conclusions: Our results indicate that the scFv-mDEC-205-gp100 targets TAA to dendritic cells in vivo for presentation on both MHC class I and II molecules. In vivo, this leads to an improved immune response and a decrease in tumor growth rate.
The Shwartzman Reaction: Pathogenetic Mechanisms and Clinical Manifestations
Authors: P F Hjort, S I Rapaport
Journal: Annual Review of Medicine (1965)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Prediction of Recurrence-Free Survival in Postoperative Non–Small Cell Lung Cancer Patients by Using an Integrated Model of Clinical Information and Gene Expression
Authors: Eung-Sirk Lee, Dae-Soon Son, Sung-Hyun Kim, Jinseon Lee, Jisuk Jo, Joungho Han, Heesue Kim, Hyun Joo Lee, Hye Young Choi, Youngja Jung, Miyeon Park, Yu Sung Lim, Kwhanmien Kim, Young Mog Shim, Byung Chul Kim, Kyusang Lee, Nam Huh, Christopher Ko, Kyunghee Park, Jae Won Lee, Yong Soo Choi, Jhingook Kim
Journal: Clinical Cancer Research (2008)

Abstract Purpose: One of the main challenges of lung cancer research is identifying patients at high risk for recurrence after surgical resection. Simple, accurate, and reproducible methods of evaluating individual risks of recurrence are needed. Experimental Design: Based on a combined analysis of time-to-recurrence data, censoring information, and microarray data from a set of 138 patients, we selected statistically significant genes thought to be predictive of disease recurrence. The number of genes was further reduced by eliminating those whose expression levels were not reproducible by real-time quantitative PCR. Within these variables, a recurrence prediction model was constructed using Cox proportional hazard regression and validated via two independent cohorts (n = 56 and n = 59). Results: After performing a log-rank test of the microarray data and successively selecting genes based on real-time quantitative PCR analysis, the most significant 18 genes had P values of &amp;lt;0.05. After subsequent stepwise variable selection based on gene expression information and clinical variables, the recurrence prediction model consisted of six genes (CALB1, MMP7, SLC1A7, GSTA1, CCL19, and IFI44). Two pathologic variables, pStage and cellular differentiation, were developed. Validation by two independent cohorts confirmed that the proposed model is significantly accurate (P = 0.0314 and 0.0305, respectively). The predicted median recurrence-free survival times for each patient correlated well with the actual data. Conclusions: We have developed an accurate, technically simple, and reproducible method for predicting individual recurrence risks. This model would potentially be useful in developing customized strategies for managing lung cancer.
<i>FUT2</i>: filling the gap between genes and environment in Behçet's disease?
Authors: Joana M Xavier, Farhad Shahram, Inês Sousa, Fereydoun Davatchi, Mafalda Matos, Bahar Sadeghi Abdollahi, João Sobral, Abdolhadi Nadji, Manuela Oliveira, Fahmida Ghaderibarim, Niloofar Mojarad Shafiee, Sofia A Oliveira
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To identify new susceptibility loci for Behçet's disease (BD), we performed a genome-wide association study (GWAS) using DNA pooling. Methods Two replicate pools of 292 Iranian BD cases and of 294 age- and sex-matched controls were allelotyped in quadruplicate on the Affymetrix Genome-Wide Human SNP Array 6.0. Of the 51 top markers, 47 were technically validated through individually genotyping. Replication of validated single nucleotide polymorphisms (SNPs) was performed in an independent Iranian dataset (684 cases and 532 controls). Results In addition to the well-established HLA-B locus, rs7528842 in a gene desert on chromosome 1p21.2, and rs632111 at the 3′UTR of FUT2 were associated in both the discovery and replication datasets (individually and in combination). However, only the FUT2 SNP was associated in a previous GWAS for BD in Turkish people. Fine-mapping of FUT2 in the full Iranian dataset showed additional associations in five coding SNPs (2.97E-06<pcombined<1.34E-04), including the rs601338 nonsense (W143X) variant which, in Caucasians, determines the secretion of the H antigen (precursor of the ABO blood group antigens) in body fluids and on the intestinal mucosa. Meta-analysis with the published Turkish GWAS data strengthened the FUT2 associations (4.78E-09<pmeta<1.66E-07). Conclusions This study suggests for the first time a putative link between a specific gene and environment in the aetiopathogenesis of BD. The non-secretor phenotype affects mucosal glycosylation, which may explain its known association with dysbiosis and altered susceptibility to infections. A different antigenic stimulation in early life and consequent increased propensity for autoimmunity and inflammation may contribute to BD development.
Plasma Carotenoids and Onset of Dysglycemia in an Elderly Population
Authors: Tasnime N. Akbaraly, Annick Fontbonne, Alain Favier, Claudine Berr
Journal: Diabetes Care (2008)

The hypothesis of carotenoid having a preventive role in diabetes is suggested by their antioxidant properties. In this report, we investigated the relationship between baseline total plasma carotenoid levels and 9-year onset of dysglycemia (impaired fasting glucose or type 2 diabetes) in a healthy elderly population.The Epidemiology of Vascular Ageing Study is a 9-year longitudinal study including 1,389 volunteers aged 59-71 years. Fasting plasma glucose was measured at baseline and at 2, 4, and 9 years after inclusion. The relationship between plasma carotenoid at baseline and incidence of dysglycemia was determined by Cox proportional hazards regression analysis adjusting for potential confounders.At 9 years, 127 incident cases of dysglycemia had occurred. Risk of dysglycemia was significantly lower in participants with plasma carotenoid in the highest quartile (Q4) compared with participants in the lowest quartile (Q1) (Q4 vs. Q1: relative risk 0.26 [95% CI 0.14-0.49], P < 10(-4); Q3 vs. Q1: 0.55 [0.34-0.89], P = 0.01; and Q2 vs. Q1: 0.82 [0.51-1.31], P = 0.40). After controlling for sociodemographic variables, lifestyle habits, cardiovascular disease, blood pressure, BMI, and lipid profile, risk of dysglycemia remained significantly lower in participants in the highest quartile of total plasma carotenoid compared with participants in the lowest quartile (Q4 vs. Q1: 0.42 [0.22-0.82], P = 0.01; Q3 vs. Q1: 0.69 [0.41-1.15], P = 0.16; and Q2 vs. Q1: 0.80 [0.48-1.32], P = 0.38).This study prospectively confirms that plasma carotenoid levels have an independent relationship to onset of dysglycemia.
Successful treatment of acrodermatitis continua suppurativa with topical tacrolimus 0.1% ointment
Authors: D. Wilsmann-Theis, T. Hagemann, H. Dederer, J. Wenzel, T. Bieber, N. Novak
Journal: British Journal of Dermatology (2004)

Acrodermatitis continua suppurativa of Hallopeau (ACS) is a rare pustular variant of psoriasis in which numerous treatment modalities have been used without any consistent long-term effect. We report for the first time two patients with ACS which was successfully treated with topical tacrolimus 0·1% ointment. Our observations raise hopes that this new treatment strategy for ACS may constitute a novel effective therapeutic option for this recalcitrant condition.
Dissecting the roles of DR4, DR5 and c-FLIP in the regulation of Geranylgeranyltransferase I inhibition-mediated augmentation of TRAIL-induced apoptosis
Authors: Shuzhen Chen, Lei Fu, Shruti M Raja, Ping Yue, Fadlo R Khuri, Shi-Yong Sun
Journal: Molecular Cancer (2010)

Abstract Background Geranylgeranyltransferase I (GGTase I) has emerged as a cancer therapeutic target. Accordingly, small molecules that inhibit GGTase I have been developed and exhibit encouraging anticancer activity in preclinical studies. However, their underlying anticancer mechanisms remain unclear. Here we have demonstrated a novel mechanism by which GGTase I inhibition modulates apoptosis. Results The GGTase I inhibitor GGTI-298 induced apoptosis and augmented tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis in human lung cancer cells. GGTI-298 induced DR4 and DR5 expression and reduced c-FLIP levels. Enforced c-FLIP expression or DR5 knockdown attenuated apoptosis induced by GGTI-298 and TRAIL combination. Surprisingly, DR4 knockdown sensitized cancer cells to GGTI298/TRAIL-induced apoptosis. The combination of GGTI-298 and TRAIL was more effective than each single agent in decreasing the levels of IκBα and p-Akt, implying that GGTI298/TRAIL activates NF-κB and inhibits Akt. Interestingly, knockdown of DR5, but not DR4, prevented GGTI298/TRAIL-induced IκBα and p-Akt reduction, suggesting that DR5 mediates reduction of IκBα and p-Akt induced by GGTI298/TRAIL. In contrast, DR4 knockdown further facilitated GGTI298/TRAIL-induced p-Akt reduction. Conclusions Both DR5 induction and c-FLIP downregulation contribute to GGTI-298-mediated augmentation of TRAIL-induced apoptosis. Moreover, DR4 appears to play an opposite role to DR5 in regulation of GGTI/TRAIL-induced apoptotic signaling.
Delta-9-tetrahydrocannabinol may palliate altered chemosensory perception in cancer patients: results of a randomized, double-blind, placebo-controlled pilot trial
Authors: T.D. Brisbois, I.H. de Kock, S.M. Watanabe, M. Mirhosseini, D.C. Lamoureux, M. Chasen, N. MacDonald, V.E. Baracos, W.V. Wismer
Journal: Annals of Oncology (2011)
Radioligand binding characteristics of β2–adrenoceptors of cultured melanoma cells
Authors: V. STEINKRAUS, MONIKA NOSE, H. MENSING, CHRISTA KORNER
Journal: British Journal of Dermatology (1990)

Journal Article Radioligand binding characteristics of β2–adrenoceptors of cultured melanoma cells Get access V. STEINKRAUS, V. STEINKRAUS Abteilung Allgemeine Pharmakologie, Universität Hamburg, Hamburg, F.R.G. Dr V.Steinkraus, Abteilung Allgemeine Pharmakologie, Universitäts‐Krankenhaus Eppendorf, Universität Hamburg, Martinistrasse 52, 2000 Hamburg 20, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar MONIKA NOSE, MONIKA NOSE Abteilung Allgemeine Pharmakologie, Universität Hamburg, Hamburg, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar H. MENSING, H. MENSING Hautklinik, Universitäts‐Krankenhaus Eppendorf, Universität Hamburg, Hamburg, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar CHRISTA KÖRNER CHRISTA KÖRNER Hautklinik, Universitäts‐Krankenhaus Eppendorf, Universität Hamburg, Hamburg, F.R.G. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 123, Issue 2, 1 August 1990, Pages 163–170, https://doi.org/10.1111/j.1365-2133.1990.tb01843.x Published: 01 August 1990
Degree of renal artery stenosis alters nitric oxide regulation of renal hemodynamics.
Authors: D H Sigmon, W H Beierwaltes
Journal: Journal of the American Society of Nephrology (1994)

Endothelium-derived nitric oxide (EDNO) maintains RBF in normal kidneys and to the nonclipped kidney of two-kidney, one-clip (2K, 1C) renovascular hypertensive rats. However, in clipped kidneys with severe renal stenosis, EDNO has been reported not to influence RBF, and it was suggested that low perfusion diminishes the stimulus of shear stress for EDNO synthesis. It was hypothesized that lesser degrees of renal artery stenosis would allow greater renal perfusion and, hence, a greater role for EDNO in maintaining RBF in the clipped kidney. The renal response to EDNO synthesis inhibition was studied with 10 mg/kg body wt N omega-nitro-L-arginine methyl ester (L-NAME). Four weeks after clipping, rats had different degrees of (functional) renal artery stenosis as determined by the ratio (R) of RBF (per gram kidney weight) in the nonclipped to clipped kidney. Stenosis was classified as either mild (R < or = 1.25) or moderate (R > or = 1.30). Both groups were similarly hypertensive (146 +/- 3 versus 148 +/- 6 mm Hg, respectively) and responded to L-NAME with a 42 mm Hg rise in blood pressure. In 2K,1C rats with mild renal artery stenosis, the renal response to L-NAME was similar in both nonclipped and clipped kidneys. RBF decreased by 17 to 19% (P < 0.005) and renal vascular resistance (RVR) increased by 59 to 63% (P < 0.005). When renal perfusion pressure was controlled, the decrease in RBF was exaggerated 3.6-fold in the nonclipped but only 2.3-fold in the clipped kidney, whereas the RVR increased proportionally.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of 303 Ro/SS-A antibody-positive patients: is this antibody a possible marker for malignancy?
Authors: B.C. Böckle, G. Stanarevic, G. Ratzinger, N.T. Sepp
Journal: British Journal of Dermatology (2012)

Background The risk of cancer in patients with autoimmune diseases has been investigated in several studies. Ro/SS‐A antibodies are frequent and specific autoantibodies among patients with various autoimmune diseases. Objectives To assess the risk of cancer in individuals with positive Ro/SS‐A antibodies and to analyse their clinical and laboratory characteristics. Methods Consecutive patients (n =303) with Ro/SS‐A antibody positivity were collected during 11 years in our outpatient clinic for autoimmune diseases and were retrospectively analysed. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for all cancers were calculated. In addition, we identified further clinical and laboratory characteristics of Ro/SS‐A antibody‐positive patients indicating the development or existence of a malignancy. Results Fifty (16·5%) patients were diagnosed with malignancies. Ro/SS‐A antibody was strongly associated with malignant diseases (SIR 2·6, 95% CI 1·9–6·1), particularly melanoma (SIR 33·3, 95% CI 5·2–188·6), T‐cell lymphoma (SIR 16·7, 95% CI 2·9–128·9), non‐Hodgkin lymphoma (SIR 10·6, 95% CI 1·5–78·9) and breast carcinoma (SIR 4·98, 95% CI 1·3–28·3). Logistic regression modelling revealed that Ro/SS‐A antibody‐positive patients aged 55 years or older, presenting with fever, anaemia and cutaneous lupus erythematosus, have a greater probability of developing cancer and are considered high‐risk patients, as compared with Ro/SS‐A antibody‐positive patients with none of the mentioned clinical criteria. Conclusions In our cohort of Ro/SS‐A antibody‐positive patients, an overall increased risk of malignancy was noticed. Regular screening tests including imaging and laboratory values are justified in Ro/SS‐A antibody‐positive patients who exhibit the mentioned clinical criteria.
Production and physiological actions of anandamide in the vasculature of the rat kidney.
Authors: D G Deutsch, M S Goligorsky, P C Schmid, R J Krebsbach, H H Schmid, S K Das, S K Dey, G Arreaza, C Thorup, G Stefano, L C Moore
Journal: Journal of Clinical Investigation (1997)

The endogenous cannabinoid receptor agonist anandamide is present in central and peripheral tissues. As the kidney contains both the amidase that degrades anandamide and transcripts for anandamide receptors, we characterized the molecular components of the anandamide signaling system and the vascular effects of exogenous anandamide in the kidney. We show that anandamide is present in kidney homogenates, cultured renal endothelial cells (EC), and mesangial cells; these cells also contain anandamide amidase. Reverse-transcriptase PCR shows that EC contain transcripts for cannabinoid type 1 (CB1) receptors, while mesangial cells have mRNA for both CB1 and CB2 receptors. EC exhibit specific, high-affinity binding of anandamide (Kd = 27.4 nM). Anandamide (1 microM) vasodilates juxtamedullary afferent arterioles perfused in vitro; the vasodilation can be blocked by nitric oxide (NO) synthase inhibition with L-NAME (0.1 mM) or CB1 receptor antagonism with SR 141716A (1 microM), but not by indomethacin (10 microM). Anandamide (10 nM) stimulates CB1-receptor-mediated NO release from perfused renal arterial segments; a similar effect was seen in EC. Finally, anandamide (1 microM) produces a NO-mediated inhibition of KCl-stimulated [3H]norepinephrine release from sympathetic nerves on isolated renal arterial segments. Hence, an anandamide signaling system is present in the kidney, where it exerts significant vasorelaxant and neuromodulatory effects.
Anaplasma phagocytophilum is not an aetiological agent of fever of intermediate duration in Gran Canaria (Spain)
Authors: M. Bolaños, E. Santana, C. Carranza, P. Anda, I. Jado, M. Hernández-Cabrera, A.M. Martín-Sánchez, J.L. Pérez-Arellano
Journal: Clinical Microbiology and Infection (2009)
Occupational asthma and contact dermatitis in a spray painter after introduction of an aziridine cross-linker.
Authors: C T Leffler, D K Milton
Journal: Environmental Health Perspectives (1999)

A 23-year-old spray painter developed contact dermatitis and respiratory difficulty characterized by small airways obstruction shortly after the polyfunctional aziridine cross-linker CX-100 began to be used in his workplace as a paint activator. The symptoms resolved after he was removed from the workplace and was treated with inhaled and topical steroids. Painters may have an increased risk of asthma due to exposure to a variety of agents, such as isocyanates, alkyd resins, and chromates. This case illustrates the importance of using appropriate work practices and personal protective equipment to minimize exposure. Occupational asthma is diagnosed by a history of work-related symptoms and exposure to known causative agents. The diagnosis is confirmed by serial pulmonary function testing or inhalational challenge testing. The risk of asthma attributable to occupational exposures is probably underappreciated due to underreporting and to inappropriate use of narrow definitions of exposure in epidemiologic studies of attributable risk.
Response to Open Peer Commentaries on “The Ethics of Advertising for Health Care Services”
Authors: Yael Schenker, Robert M. Arnold, Alex John London
Journal: The American Journal of Bioethics (2014)

We appreciate the breadth of thoughtful comments on our article, “The Ethics of Advertising for Health Care Services” (Schenker, Arnold, and London 2014). Most commentators agreed with our assertio...
TGFB1 promoter polymorphism C-509T and pathophysiology of asthma
Authors: Tetsuya Ueda, Akio Niimi, Hisako Matsumoto, Masaya Takemura, Masafumi Yamaguchi, Hirofumi Matsuoka, Makiko Jinnai, Kazuo Chin, Masayoshi Minakuchi, Lei Cheng, Taro Shirakawa, Michiaki Mishima
Journal: Journal of Allergy and Clinical Immunology (2007)
Pharmacogenetics of ABCG2 and Adverse Reactions to Gefitinib
Authors: George Cusatis, Vanesa Gregorc, Jing Li, Anna Spreafico, Roxann G. Ingersoll, Jaap Verweij, Vienna Ludovini, Eugenio Villa, Manuel Hidalgo, Alex Sparreboom, Sharyn D. Baker
Journal: JNCI Journal of the National Cancer Institute (2006)

Gefitinib is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase with activity in non–small-cell lung cancer. Diarrhea and skin toxicity are prominent gefitinib-related adverse events that potentially limit its use. Gefitinib is a substrate for ABCG2 (ABCP, BCRP, MXR), a polymorphic efflux transporter protein that is highly expressed in the intestines and liver. Here we investigated associations between allelic variants of EGFR, ABCG2, and the transporter protein ABCB1 with diarrhea and skin toxicity in gefitinib-treated patients. One variant, a common functional single-nucleotide polymorphism (SNP) in the ABCG2 gene, was associated with diarrhea in 124 patients treated with oral gefitinib 250 mg once daily; seven (44%) of 16 patients heterozygous for ABCG2 421C>A (Q141K) developed diarrhea, versus only 13 (12%) of 108 patients homozygous for the wild-type sequence ( P = .0046). However, this SNP was not associated with skin toxicity ( P = .99). The finding suggests that patients with reduced ABCG2 activity due to a common genetic variant are at increased risk for substrate drug–induced diarrhea, with implications for optimizing treatment with such agents.
Quantification of collateral resistance in acute and chronic experimental coronary occlusion in the dog.
Authors: W Schaper, W Flameng, B Winkler, B Wüsten, W Türschmann, G Neugebauer, M Carl, S Pasyk
Journal: Circulation Research (1976)

The resistance to coronary blood flow in various parts of the myocardium was studied with the tracer microspheres technique before and immediately after an acute coronary occlusion and several weeks after a more slowly occurring coronary occlusion by Ameroid constrictor. All experiments were carried out in the isolated, metabolically supported, empty, beating dog heart at maximal coronary vasodilation induced with adenosine. Coronary resistance of the normal empty beating heart at maximal coronary vasodilation was 0.20 mm mm Hg/(ml/min) per 100 g of tissue (subepicardium) and 0.16 mm Hg/(ml/min) per 100 g of tissue (subendocardium). After acute coronary occlusion the perfusion of the subtended myocardium was maintained at a much lower level by way of collateral vessels, which showed a resistance to flow of 3.52 mm Hg/(ml/min) per 100 g. If coronary artery occlusion proceeded more slowly the collateral vessels became more functional and myocardial infarction was avoided. During collateral enlargement collateral resistance fell from 3.52 to 0.22 mm Hg/(ml/min) per 100 g within a period of 8 weeks after implantation of the constricting device. The degree of compensation by collaterals for the loss of the occluded native coronary artery was 33% of its former conductance.