tbuckley/cabot-search huggingface dataset:
Cis binding between inhibitory receptors and MHC class I can regulate mast cell activation
Authors: Ai Masuda, Akira Nakamura, Tsutomu Maeda, Yuzuru Sakamoto, Toshiyuki Takai
Journal: The Journal of Experimental Medicine (2007)

Allergy is caused by immune effector cells, including mast cells and basophils. Cellular signaling that activates these effector cells is regulated by different inhibitory receptors on their surface. We show that human leukocyte immunoglobulin (Ig)-like receptor (LILR) B2 and its mouse orthologue, paired Ig-like receptor (PIR)–B, constitutively associate to major histocompatibility complex (MHC) class I on the same cell surface (in cis). The IgE-mediated effector responses were augmented in β2-microglobulin (β2m) and PIR-B–deficient mast cells. In addition, the increased cytokine production of β2m-deficient mast cells was not affected by the co-culture with MHC class I–positive mast cells, showing that less cis interaction between PIR-B and MHC class I on mast cells led to the increased cytokine release. Thus, the constitutive cis binding between LILRB2 or PIR-B and MHC class I has an essential role in regulating allergic responses.
Clinical and immunologic effects of long‐term sublingual immunotherapy in asthmatic children sensitized to mites:a double‐blind, placebo‐controlled study
Authors: G. B. Pajno, L. Morabito, G. Barberio, S. Parmiani
Journal: Allergy (2000)

Background: Immunotherapy through local routes is thought to be a valuable therapeutic option for respiratory allergy. We investigated the clinical efficacy and immunologic effects of sublingual immunotherapy (SLIT) in asthmatic children with mite‐induced respiratory allergy. Methods: Twenty‐four patients (age range 8–15 years), suffering from mild to moderate asthma, with single sensitization to mite allergen, were enrolled. After a 1‐year observation phase, patients were randomly allocated to one of two groups, and were given SLIT (sublingual‐spit) as drops for 2 years according to a double‐blind, placebo‐controlled (DBPC) design. Symptoms/medication scores (diary card), visual analog scale, and immunologic parameters (house‐dust‐mite [HDM]‐specific IgE, and total HDM‐specific IgG and IgG4) were determined during the observation phase and during the DBPC treatment period. Results: Twenty‐one patients completed the study. At the beginning of the treatment, no difference in environmental allergenic pressure could be shown between the groups. After 2 years of therapy, there was a significant decrease in asthmatic symptoms ( P =0.0001) and medication use ( P =0.0001) in the active group compared to the placebo group. The visual analog score on overall asthma symptoms improved in the SLIT group ( P =0.0001), but not in the placebo group. Nevertheless, the immunologic results did not show significant differences in HDM‐specific IgE and total HDM‐specific IgG or IgG4 between the active and placebo groups ( P =NS). No relevant side‐effects were recorded throughout the study. Conclusions: Our results suggest that treatment for 2 years with SLIT is clinically safe and effective in significantly decreasing respiratory symptoms in children with mild to moderate asthma sensitized to HDM. On the other hand, the lack of changes of the immunologic parameters calls for further investigations with special reference to kinetics and mechanism(s) of action of this mode of treatment.
B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders
Authors: Ryan A. Wilcox, Andrew L. Feldman, David A. Wada, Zhi-Zhang Yang, Nneka I. Comfere, Haidong Dong, Eugene D. Kwon, Anne J. Novak, Svetomir N. Markovic, Mark R. Pittelkow, Thomas E. Witzig, Stephen M. Ansell
Journal: Blood (2009)
Headache and visual aura in an immunocompromised patient
Authors: H. Tharmalingam, T. C. Morris, J. Farnsworth, E. J. Kanfer
Journal: BMJ (2012)

A 38 year old HIV negative South African man was diagnosed in 2007 with stage IVB Hodgkin’s lymphoma. Conventional chemotherapy and radiotherapy had no effect, so in March 2007 he underwent an autologous stem cell transplant. Relapses in 2009 and 2010 resulted in two allogeneic stem cell transplants, after he was conditioned with fludarabine, cyclophosphamide, and anti-thymocyte globulin. After his second transplant he developed grade four graft versus host disease that affected the liver and gut, and in December 2010 he was started on an immunosuppressive regimen of prednisolone and ciclosporin.

In June 2011 he re-presented with a one week history of fever, vomiting, and malaise, followed by severe headache and visual aura. On examination he was cachectic with mild ankle oedema and a fever (39.2°C). The rest of the examination was unremarkable. His peripheral white blood cell count was 0.7×109/L (normal range 4-11), neutrophils were 0.1×109/L (2-7.5), platelets 22×109/L (150-400), and haemoglobin 98 g/L (130-180). Liver function tests showed alanine transaminase 362 U/L (21-72), alkaline phosphatase 960 U/L (30-120), bilirubin 61 μmol/L (3-22; 1 μmol/L=0.06 mg/dL), and albumin 28 g/L (35-50). C reactive protein was raised at 2743 nmol/L (<45 nmol/L; 91 nmol/L=0.1 mg/L). In light of his neurological symptoms, he underwent magnetic resonance imaging (MRI) of the brain, the results of which are shown in fig 1⇓.



Fig 1 Axial T1 weighted magnetic resonance image of the brain with gadolinium contrast





### 1 What does the contrast magnetic resonance image show?

#### Short answer

The contrast MRI of the brain shows a large ring enhancing lesion in the right parietal lobe. The …
High F-18 FDG Uptake in Bone Marrow by Cytokines Secreting Ectopic Mucoepidermoid Carcinoma
Authors: Hans Balink, Hans Nabers, Robby E. Kibbelaar
Journal: Clinical Nuclear Medicine (2009)

A 57-year-old woman, just returned from a bicycling holiday in the mountains, presented with discomfort, hoarseness and chronic cough complaints. After chest x-ray, bronchoscopy and fluoro-deoxy-glucose positron emission tomography/computed tomography (F-18 FDG PET/CT), a diagnosis of a tumor in the bronchus of the right upper lobe with obstruction pneumonia was made. After lobectomy of the right upper lobe, pathology revealed an ectopic bronchial low-grade mucoepidermoid carcinoma.The diffuse high FDG uptake in the bone marrow standardized uptake value (SUV mean 3.6 and max 5.2) is unlikely to be related to bone marrow stimulation due to pneumonia, but correlates with a high serum level of correlated with transforming growth factor-beta (TGF-beta1) secreted by the low-grade bronchial mucoepidermoid carcinoma.
The Role of the IGF System in Cancer Growth and Metastasis: Overview and Recent Insights
Authors: Amir Abbas Samani, Shoshana Yakar, Derek LeRoith, Pnina Brodt
Journal: Endocrine Reviews (2007)

IGF-I receptor (IGF-IR) signaling and functions are mediated through the activities of a complex molecular network of positive (e.g., type I IGF) and negative (e.g., the type II IGF receptor, IGF-IIR) effectors. Under normal physiological conditions, the balance between the expression and activities of these molecules is tightly controlled. Changes in this delicate balance (e.g., overexpression of one effector) may trigger a cascade of molecular events that can ultimately lead to malignancy. In recent years, evidence has been mounting that the IGF axis may be involved in human cancer progression and can be targeted for therapeutic intervention. Here we review old and more recent evidence on the role the IGF system in malignancy and highlight experimental and clinical studies that provide novel insights into the complex mechanisms that contribute to its oncogenic potential. Controversies arising from conflicting evidence on the relevance of IGF-IR and its ligands to human cancer are discussed. Our review highlights the importance of viewing the IGF axis as a complex multifactorial system and shows that changes in the expression levels of any one component of the axis, in a given malignancy, should be interpreted with caution and viewed in a wider context that takes into account the expression levels, state of activation, accessibility, and functionality of other interacting components. Because IGF targeting for anticancer therapy is rapidly becoming a clinical reality, an understanding of this complexity is timely because it is likely to have an impact on the design, mode of action, and clinical outcomes of newly developed drugs.
IS DEFIBRILLATION TESTING NEEDED FOR RIGHT PECTORAL ICD IMPLANTS?
Authors: William Brabham, Jason A. Goebel, Anbukarasi Maran, Frederick W. Funke, Frank A. Cuoco, Robert B. Leman, J. Lacy Sturdivant, J. Marcus Wharton, Michael R. Gold
Journal: Journal of the American College of Cardiology (2011)
Histologic predictors of acute cardiac rejection in human endomyocardial biopsies: A multivariate analysis
Authors: Ahvie Herskowitz, Lisa M. Soule, E. David Mellits, Thomas A. Traill, Stephen C. Achuff, Bruce A. Reitz, A. Michael Borkon, William A. Baumgartner, Kenneth L. Baughman
Journal: Journal of the American College of Cardiology (1987)
Abstract B43: Comparative proteomic analysis of colorectal cell lines to identify biomarkers for the prediction of intrinsic resistance to FOLFOX chemotherapy
Authors: Florian T. Unger, Markus Meyer, Monika Spörl, Agnieszka Harasym, Kevin Sullivan, Hartmut Juhl, Kerstin A. David
Journal: Clinical Cancer Research (2010)

Abstract As there is a great interpatient variability in drug response caused by the individual geno- and phenotype the choice of optimal chemotherapy should be tailored for each patient. Intrinsic drug resistance is one of the main reasons for therapeutic ineffectiveness of first line therapy and recurrence in colorectal cancer. To advance individualized chemotherapy and understanding of drug resistance mechanisms, predictive biomarkers which indicate individual drug response of patients are urgently needed. The prediction of response to first line therapy will identify subgroups of patients who benefit from treatment and thus avoid ineffective treatment and associated side effects. In this study, several commercially available cell lines as well as primary epithelial mixed cultures and clonal cell lines established from colorectal cancer patients were treated with different drugs, such as 5-fluorouracil, oxaliplatin, and drug combinations, e.g., FOLFOX. The determination of chemosensitivity of these cell lines to drug treatment was performed using two different assays, the ATPlite™-(Perkin Elmer) and FMC-assay (according to Larsson et al.). Both assays showed time- and dose-dependent drug responses which differed significantly among the 18 colorectal cell cultures. The analysis of obtained in vitro chemosensitivity data allowed us to cluster sensitive versus resistant cell lines by determining IC50-values. For the discovery of differentially expressed proteins which might be linked to a specific phenotypes of intrinsic chemoresistance we generated protein expression patterns from all 18 cell lines using a combination of reversed phase highperformance liquid chromatography and matrix-assisted laser desorption/ionization mass spectrometry (RP-HPLC MALDI MS). Up to 3500 m/z ion signals in the molecular mass range between 2500-35000 m/z were detected reflecting a complex pattern of small proteins and peptides. For protein identification, RP-HPLC fractionated samples were purified and digested by trypsin. Fragments of interest were subjected to MS/MS analysis in the TOF/TOF mode. The corresponding MS/MS spectra were used to search the NCBInr database using MASCOT software. Based on these data, we hope to gain more understanding of the biological processes of chemoresistance concerning important cellular drug responses (e.g., signal transduction pathways) and thereby obtain insight into new drug targets for future therapeutic intervention. Citation Information: Clin Cancer Res 2010;16(14 Suppl):B43.
Increased Risk of Left Heart Valve Regurgitation Associated With Benfluorex Use in Patients With Diabetes Mellitus
Authors: Christophe Tribouilloy, Dan Rusinaru, Sylvestre Maréchaux, Antoine Jeu, Stéphane Ederhy, Erwan Donal, Patricia Réant, Elise Arnalsteen, Jacques Boulanger, Pierre-Vladimir Ennezat, Thierry Garban, Yannick Jobic
Journal: Circulation (2012)

Background— Benfluorex was withdrawn from European markets in June 2010 after reports of an association with heart valve lesions. The link between benfluorex and valve regurgitations was based on small observational studies and retrospective estimations. We therefore designed an echocardiography-based multicenter study to compare the frequency of left heart valve regurgitations in diabetic patients exposed to benfluorex for at least 3 months and in diabetic control subjects never exposed to the drug. Methods and Results— This reader-blinded, controlled study conducted in 10 centers in France between February 2010 and September 2011 prospectively included 376 diabetic subjects previously exposed to benfluorex who were referred by primary care physicians for echocardiography and 376 diabetic control subjects. Through the use of propensity scores, 293 patients and 293 control subjects were matched for age, sex, body mass index, smoking, dyslipidemia, hypertension, and coronary artery disease. The main outcome measure was the frequency of mild or greater left heart valve regurgitations. In the matched sample, the frequency and relative risk (odds ratio) of mild or greater left heart valve regurgitations were significantly increased in benfluorex patients compared with control subjects: 31.0% versus 12.9% (odds ratio, 3.55; 95% confidence interval, 2.03–6.21) for aortic and/or mitral regurgitation, 19.8% versus 4.7% (odds ratio, 5.29; 95% confidence interval, 2.46–11.4) for aortic regurgitation, and 19.4% versus 9.6% (odds ratio, 2.38; 95% confidence interval, 1.27–4.45) for mitral regurgitation. Conclusions— Our results indicate that the use of benfluorex is associated with a significant increase in the frequency of left heart valve regurgitations in diabetic patients. The natural history of benfluorex-induced valve abnormalities needs further research.
Cardiac Dysfunction Assessed by Echocardiographic Tissue Doppler Imaging Is an Independent Predictor of Mortality in the General Population
Authors: Rasmus Mogelvang, Peter Sogaard, Sune A. Pedersen, Niels T. Olsen, Jacob L. Marott, Peter Schnohr, Jens P. Goetze, Jan S. Jensen
Journal: Circulation (2009)

Background— Tissue Doppler imaging (TDI) detects left ventricular dysfunction in patients with heart failure and normal ejection fraction, but the prognostic significance of left ventricular dysfunction by TDI in the general population is unknown. Methods and Results— Within the Copenhagen City Heart Study, a large community-based population study, cardiac function was evaluated in 1036 participants by both conventional echocardiography and TDI. Averages of peak systolic (s′), early diastolic (e′), and late diastolic (a′) velocities from 6 mitral annular sites were used. TDI was furthermore quantified by a combined index (eas index) of diastolic and systolic performance: e′/(a′×s′). During follow-up (median, 5.3 years), 90 participants died. Left ventricular dysfunction by TDI, in terms of low s′ (hazard ratio, 1.23 per 1-cm/s decrease; P &lt;0.05) and a′ (hazard ratio, 1.20 per 1-cm/s decrease; P =0.001), were significant predictors of death in Cox proportional-hazards models adjusted for clinical variables (age, sex, body mass index, heart rate, hypertension, diabetes mellitus, and ischemic heart disease) and conventional echocardiography. The adjusted hazard ratio for death in the third tertile compared with the first tertile of the combined index of systolic and diastolic performance by TDI was 2.5 ( P &lt;0.005). Conclusions— In the general population, in which most are free of left ventricular systolic dysfunction and restrictive diastolic filling using conventional echocardiographic parameters, left ventricular dysfunction by TDI is a powerful and independent predictor of death, especially when systolic performance and diastolic performance are considered together, recognizing their interdependency and their complex relation to deteriorating cardiac function.
Mobile phone use is not linked to brain tumours, large Scandinavian study finds
Authors: J. H. Tanne
Journal: BMJ (2009)

Mobile phone use rose dramatically in the early 1990s, but five to 10 years later there was no increase in the incidence of brain tumours in Denmark, Finland, Norway, and Sweden, a new study has found.

The authors of the study, published in the Journal of the National Cancer Institute (2009;101:1721-4, doi:10.1093/jnci/djp415), wrote, “Radio frequency electromagnetic fields emitted from mobile phones have been proposed as a risk factor for brain tumors; however, …
Putting Ad Hoc PCI on Pause
Authors: Brahmajee K. Nallamothu, Harlan M. Krumholz
Journal: JAMA (2010)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
RsaI polymorphism at the cytochrome P4502E1 locus and risk of hepatocellular carcinoma.
Authors: J M Ladero, J A Agundez, A Rodriguez-Lescure, M Diaz-Rubio, J Benitez
Journal: Gut (1996)

CYP2E1, the coding gene for the ethanol inducible cytochrome P4502E1, is polymorphic at the RsaI restriction site in the 5' flanking region. The mutant allele c2 has a higher transcriptional activity than the wild-type gene c1. P4502E1 catalyses the activation of several environmental carcinogens at a rate that is increased, if only moderately, by longterm ethanol intake.To establish the distribution of CYP2E1 RsaI polymorphism in patients with hepatocellular carcinoma and to evaluate its possible role in the multifactorial pathogenesis of this tumour.101 (84 males) patients with hepatocellular carcinoma and 178 (128 males) healthy controls of the same ethnic (white) and Spanish origin.After extraction of DNA from white blood cells, alleles c1 and c2 of CYP2E1 were identified by restriction fragment length polymorphism (RFLP) with endonuclease RsaI.Homozygous c1c1: 90 patients and 169 controls; heterozygous c1c2: 11 and 9; homozygous c2c2: none (non-significant difference). C2 allele frequencies: 0.055 in patients, 0.025 in controls (non-significant difference) and 0.108 in the 37 patients who had drunk more than 50 g of ethanol/day (p = 0.0035, odds ratio versus controls: 4.67; 95% confidence limits 1.57 to 13.81).The carrier state of one copy of the c2 CYP2E1 gene increases the risk of hepatoma in previously regular ethanol users with chronic liver disease.
Evaluation of a cyclophilin inhibitor in hepatitis C virus-infected chimeric mice<i>in vivo</i>
Authors: Kazuaki Inoue, Takuya Umehara, Urs T. Ruegg, Fumihiko Yasui, Tsunamasa Watanabe, Hiroshi Yasuda, Jean-Maurice Dumont, Pietro Scalfaro, Makoto Yoshiba, Michinori Kohara
Journal: Hepatology (2007)

Cyclosporin A (CsA) inhibits replication of the HCV subgenomic replicon, and this effect is believed to not be mediated by its immunosuppressive action. We found that DEBIO-025, a novel non-immunosuppressive cyclophilin inhibitor derived from CsA, inhibited HCV replication in vitro more potently than CsA. We also examined the inhibitory effect of DEBIO-025 on naive HCV genotypes 1a or 1b in vivo using chimeric mice with human hepatocytes. These mice were treated for 14 days with DEBIO-025, pegylated-interferon α−2a (Peg-IFN), a combination of either drugs, or CsA in combination with Peg-IFN. In mice treated with Peg-IFN, serum HCV RNA levels decreased approximately 10-fold whereas DEBIO-025 treatment alone did not induce any significant change. In mice treated with both DEBIO-025 and Peg-IFN, HCV RNA levels decreased more than 100-fold. All mice treated with Peg-IFN combined with CsA died within 4 days. The combination treatment of DEBIO-025 and Peg-IFN reduced HCV RNA levels and core protein expression in liver, indicating that the HCV RNA levels reduction in serum was attributable to intrahepatic inhibition of HCV replication. Conclusion: We demonstrated that DEBIO-025 was better tolerated than CsA, and that its anti-HCV effect appeared to be synergistic in combination with Peg-IFN in vivo. (HEPATOLOGY 2007;45:921–928.)
Platelet Phosphatides: Their Separation, Identification, and Clotting Activity1
Authors: Aaron J. Marcus, Theodore H. Spaet
Journal: Journal of Clinical Investigation (1958)

Agents capable of accelerating the conversion of prothrombin into thrombin in the presence of Ca+ may be said to have thromboplastic activity.Early studies of thromboplastic activity were car- ried out with materials derived from tissues.Wooldridge (1, 2), in 1886, produced intravascu- lar clotting in animals by the intravenous admini- stration of aqueous extracts of red blood cells, white blood cells, and tissues.He was of the opinion that the active factor in these extracts was a protein-lecithin compound.In 1912, Ho- well (3) also reported that a lipoprotein was re- sponsible for the thromboplastic activity of aque- ous tissues extracts.The lipid portion was a phosphatide which could be separated from the protein with fat solvents, and had the properties of "cephalin."He assumed that the thrombo- plastic activity of certain lecithins tested was due to contamination with cephalin.McLean (4, 5) extended these observations and showed that the potency of the cephalin preparation varied directly with the degree of unsaturation of the constituent fatty acids.Gratia and Levene (6) confirmed the work of Howell, using their own cephalin preparations.Wadsworth, Maltaner and Mal- taner (7-9) prepared cephalin free of lecithin and showed that the lecithin had no thromboplastic ac- tivity.Cohen and Chargaff (10) and Chargaff (11) verified that the tissue thromboplastic factor was a lipoprotein and that the lipid portion was associated with the phosphatides.It became of interest to determine whether plasma contained a thromboplastic factor anal- ogous to that found in the tissues.Wooldridge (12) suggested that a thromboplastic substance existed in plasma ("Fibrinogen-B") which united