tbuckley/cabot-search huggingface dataset:
Abstract 13773: A Novel Immunoglobulin G Autoantibody Against a Cryptic Epitope in Low Density Lipoprotein Induces Macrophage Tumour Necrosis Factor Release
Authors: Ramzi Khamis, Kevin Woollard, Joseph J Boyle, Shang-Hung Chang, Gareth Hyde, Michael Johns, Dorian O Haskard
Journal: Circulation (2014)

Introduction/Objective: Although IgG autoantibodies reacting with modified LDL have been associated with cardiovascular events, there is controversy as to whether such antibodies can be pathogenic. We set out to generate monoclonal autoantibodies reacting with LDL for further mechanistic studies. Methods/Results: We fused LDL receptor deficient (Ldlr-/-) mouse splenocytes with Sp2/0 myeloma cells, and screened hybridoma supernatants for reactivity with LDL. We selected a monoclonal IgG2b antibody, designated LO9. Variable heavy and light chain sequencing revealed somatic mutations indicative of LO9 being part of an acquired immune response. LO9 showed greater binding to unmanipulated solid phase human LDL than to Cu++ oxidised-LDL or malondialdehyde-conjugated LDL. LO9 did not react with LDL captured by immobilised anti-apoB, and binding to solid phase LDL was not inhibited by fluid phase LDL. Expression of the LO9 epitope on adherent LDL was increased by activated macrophage supernatant and this was inhibited by pepstatin A. Together, these observations suggest that LO9 reacts with a cryptic epitope in LDL unmasked by adhesion and/or the action of macrophage-derived enzyme(s). LO9 epitope expression in vivo was confirmed by immunohistochemical staining of human and mouse atherosclerosis. Following intra-venous injection of LO9 labelled with VivoTag-S 750-MAL, fluorescence molecular tomography imaging showed LO9 uptake in the aortic arch of Ldlr-/- but not wild-type animals. Confocal microscopy confirmed that LO9 localised in atherosclerotic regions beneath endothelium and in the vicinity of macrophages. In functional in vitro assays, addition of macrophages to LO9 bound to adherent LDL led to significant TNF release, an effect that was blocked by inhibition of Fc gamma receptors, and which was not seen when macrophages were incubated with adherent LDL alone. Conclusions: We believe LO9 is the first example of an IgG autoantibody that reacts with a cryptic epitope in LDL, revealed by adherence and/or by macrophage-derived enzyme(s). Binding of LO9-like IgG antibodies to LDL trapped on arterial matrix could lead to promotion of atherosclerosis via ligation of macrophage Fc gamma receptors and release of TNF and other inflammatory mediators.
AB0134 Affibody Molecules Inhibiting the Interaction between RAS and RAF Suppress the Proliferation and the Production of Inflammatory Mediators by Synovial Cells
Authors: M. Sekiguchi, T. Iwasaki, S. Shibasaki, P.-Å. Nygren, T. Gräslund, H. Sano
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ras proteins are present in rheumatoid arthritis (RA) synovial tissues, and are preferentially expressed in the intimal lining layer. Activation of Ras effecter pathways in synovial tissues, including MAP kinases, PI3K, and nuclear factor-κB, is enhanced in RA. We developed affibody molecules with the ability to selectively inhibit the interaction between H-Ras and Raf-1, from a combinatorial library displayed on bacteriophage. <h3>Objectives</h3> The present study investigated the effects of affibody molecules on synovial cell functions using human synovial fibroblast cell line. <h3>Methods</h3> Affibodys (Mw 6 kDa) were derived from one of the domains of the cell wall protein Protein A of <i>Staphylococcus aureus</i>. Using phage display library, three affibody clones which can binds to H-Ras [His6-Z<sub>(Ras521)2</sub>, His6-Z<sub>(Ras122)2</sub>, His6-Z<sub>Raf322</sub>] were screened from combinatorial library. To evaluate the specificity and affinity of the selected affibody molecules towards their respective targets, we performed real-time biospecific interaction experiments. To examine the effects of affibodies on synovial cell functions, we used a human synovial fibroblast cell line (MH7A). The proliferation was examined by a modified MTT assay. IL-6 and PGE2 productions by MH7A cells were determined by ELISA. <h3>Results</h3> Affibody molecule variants selected against H-Ras were shown to bind epitopes overlapping each other at a site that differed from that at which H-Ras interacts with Raf-1. They were shown to effectively inhibit the interaction between H-Ras and Raf-1 in a dose-dependent manner by real-time biospecific interaction experiments. Transformation of plasmids encoding His6-Z<sub>(Ras521)2</sub>, into MH7A cells induced significant amounts of His6-Z<sub>(Ras521)2</sub> proteins, as shown by Western blot analysis, and significantly inhibited the proloferation and suppressed the productions of IL-6 and PGE2 stimulated by TNF-alpha. <h3>Conclusions</h3> We have successfully selected affibody molecules specifically binding to H-Ras with high affinity. We also demonstrated that signaling through the H-Ras–Raf pathway by MH7A cells can be blocked, thereby inhibiting the productions of IL-6 and PGE2 stimulated by TNF-alpha. Molecular targeting of H-Ras-Raf-1 signaling by affibody molecules can be useful as a regulator of synovial cell functions in patients with RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2553
The Dopamine D2/D3 Receptor Antagonist APD421 in Combination with Ondansetron Effectively Prevents Acute Cisplatin-Induced Nausea and Vomiting (CINV)
Authors: J. Herrstedt, Y. Summers, G. Daugaard, T.B. Christensen, K. Holmskov, P.D. Taylor, G. Fox, A. Molassiotis
Journal: Annals of Oncology (2012)
Abstract 12295: Vascular Response to the Sodium-Glucose Cotransporter Inhibitor in Type 2 Diabetic Mice
Authors: Ying Han, Young-Eun Cho, Ramon Ayon, Minglin Pan, Anzhi Dai, Jason X.-J. Yuan, Ayako Makino
Journal: Circulation (2014)

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral drugs for the treatment of type 2 diabetes (T2D) and they reduce plasma blood glucose levels by inhibiting renal glucose reabsorption. However, there are no data investigating the vascular response to the SGLT inhibitors. This study is designed to determine whether and how phlorizin (a non-specific SGLT1 and 2 inhibitor) and canagliflozin, a FDA-approved SGLT2-specific inhibitor, regulate vascular tone in pulmonary and coronary arteries of control and T2D mice. Both phlorizin and canagliflozin induced vascular relaxation in pre-contracted pulmonary and coronary arteries. In addition, pretreatment of SGLT inhibitors significantly attenuated NO-dependent vascular relaxation in pulmonary arteries (assessed by sodium nitroprusside, a NO donor), but not in coronary arteries. We further examined the downstream of NO-dependent relaxation in pulmonary artery using a cGMP analogue and a phosphodiesterase inhibitor as well as measured membran...
The role of omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids in the treatment of major depression and Alzheimer's disease: Acting separately or synergistically?
Authors: Cai Song, Chu-Hsin Shieh, Yi-Shyuan Wu, Allan Kalueff, Siddharth Gaikwad, Kuan-Pin Su
Journal: Progress in Lipid Research (2016)
Abstract P6-09-05: Value of adding single-nucleotide polymorphism panel markers to phenotypic algorithms of breast cancer risk
Authors: Gillian Dite, Richard Allman, John L Hopper
Journal: Cancer Research (2015)

Abstract Currently, breast cancer risk prediction algorithms incorporate phenotypic risk factors, including age, family history, reproductive history and benign breast disease. Since 2007, genome-wide association studies have identified a growing number of single-nucleotide polymorphisms (SNPs) that are associated with an increased risk of breast cancer. While no single SNP is very informative on its own, a polygenic approach to genetic screening could improve estimates of individual risk, creating the possibility of screening strategies individually tailored to each woman. We studied cases and controls recruited to the Australian Breast Cancer Family Registry, to investigate whether a SNP risk score derived from a panel of 77 SNPs can improve risk estimates obtained from the commonly used breast cancer risk prediction models (BCRAT, IBIS, BRCAPRO and BOADICEA). SNP risk scores were calculated using previously published Odds Ratios (ORs) and risk-allele frequencies based on the assumption of independence of additive risks on the log OR scale. SNP risk scores were calculated by multiplying adjusted risk scores for each of the SNPs. Combined risk scores were calculated by multiplying the SNP risk score and the algorithm derived risk scores, under the assumption of independence. Overall, the inclusion of data on 77 SNPs improved the area under the receiver operating characteristic curve (AUC) for all of the breast cancer risk prediction models: Preliminary data analysis provided AUC values as follows: BCRAT+SNP = 0.656, IBIS+SNP= 0.628, BRCAPRO+SNP= 0.689, BOADICEA+SNP= 0.698. The breast cancer risk prediction models examined place different weighting on the phenotypic components. For example, the IBIS model is weighted towards uncommon high-risk phenotypes, while the BCRAT is weighted towards lower risks in the general population. A combination of the 77 SNP score and the most appropriate model might substantially improve the ability to identify high-risk women in different screening populations. Citation Format: Gillian Dite, Richard Allman, John L Hopper. Value of adding single-nucleotide polymorphism panel markers to phenotypic algorithms of breast cancer risk [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-09-05.
An Adjuvant Role for Mobile Health in Psychiatry
Authors: Honor Hsin, John Torous, Laura Roberts
Journal: JAMA Psychiatry (2016)

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 Psychiatry HomeNew OnlineCurrent IssueFor Authors Podcast 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) 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 Psychiatry journal
Innate basophil IL-4 responses against allergens, endotoxin, and cytokines require the Fc receptor γ-chain
Authors: Seiji Kamijo, Satoshi Nunomura, Chisei Ra, Yasuhiko Kanaguchi, Yusuke Suzuki, Hideoki Ogawa, Ko Okumura, Toshiro Takai
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract P375: Decade Long Trends in the Magnitude, Treatment, and Outcomes of Young Adults Hospitalized with ST-Segment Elevation Myocardial Infarction and Non-ST-Segment Elevation Myocardial Infarction
Authors: Mayra Tisminetzky, Jennifer Coukos, David McManus, Chad Darling, Samuel Joffe, Joel Gore, Darleen Lessard, Robert Goldberg
Journal: Circulation (2014)

Background: Although acute myocardial infarction (AMI) occurs primarily in the elderly, this disease also affects young adults. Few studies have, however, presented data on relatively young patients hospitalized with AMI. The objectives of this population-based study were to examine recent trends in the magnitude, management, and in-hospital and long-term-outcomes associated with either an initial ST-segment elevation acute myocardial infarction (STEMI) or non-ST-segment elevation acute myocardial infarction (NSTEMI) in patients between the ages of 30-54 years old. Methods: We reviewed the medical records of 745 residents of the Worcester (MA) metropolitan area between the ages of 30 and 54 years who were hospitalized for an initial STEMI or NSTEMI in 6 annual periods between 1997 and 2007 at 11 greater Worcester medical centers. Results: Between 1997 and 2007, the proportion of young adults hospitalized with an initial STEMI decreased from approximately two-thirds to two-fifths of all patients. Patients with STEMI were less likely to have a history of heart failure, hypertension, hyperlipidemia, and kidney disease than NSTEMI patients. Both groups were similarly treated with evidence-based therapies during their acute hospitalization with encouraging trends in the prescribing of various cardiac medications observed over time (Figures 1A and B). Important in-hospital clinical complications and mortality were low and no significant differences in these endpoints were observed between STEMI and NSTEMI patients. One year post-discharge death rates were also similar in both groups (1.9% vs. 2.8%). Conclusion: The present results demonstrate recent decreases in the proportion of relatively young patients diagnosed with an initial STEMI. Patients with STEMI and NSTEMI had similar in-hospital outcomes and long-term survival. Trends in these and other important outcomes warrant continued monitoring.
A phase I-II trial of carboplatin and 5-fluorouracil combination chemotherapy in advanced carcinoma of the head and neck.
Authors: A A Forastiere, R B Natale, B J Takasugi, M P Goren, W C Vogel, V Kudla-Hatch
Journal: Journal of Clinical Oncology (1987)

Twenty-nine patients with recurrent or advanced, incurable head and neck cancer were entered into a phase I-II trial of carboplatin in combination with 5-fluorouracil (5-FU), 1,000 mg/m2/d continuous intravenous (IV) infusion for five days every 28 days. The initial dose of carboplatin was 300 mg/m2 for patients with Karnofsky performance scores greater than or equal to 70%, and 240 mg/m2 for patients with scores of 50% to 60%. Subsequent doses were modified to achieve grade 2 myelo-suppression: WBC, 2,000 to 2,999 cells/microL; granulocytes, 1,000 to 1,499 cells/microL; and platelets, 50,000 to 75,000 cells/microL. Dose levels were 180, 240, 300, 360, and 420 mg/m2. Twenty-eight patients had squamous-cell cancers and one had an adenoid cystic carcinoma of the parotid. There were 26 patients with recurrent disease; 22 had received prior RT; only two had received other chemotherapy immediately before study entry. Three patients had newly diagnosed incurable stage IV disease. The median performance status was 80% (range, 60% to 90%). All patients had objectively measurable disease, and 28 were evaluable for response. There were three complete responses (CRs) and ten partial responses (PRs) (48% CR and PR); the median duration of response was 4.7 months (range, 1.5 to 15+ months). Dose-limiting toxicities were granulocytopenia, thrombocytopenia, and stomatitis. Prolonged myelosuppression delayed retreatment in eight patients and delayed 19 of 107 (18%) courses. Stomatitis occurred in 61% and diarrhea in 29%. 5-FU dosage was decreased in ten patients (36%) for grade 2 or greater stomatitis or diarrhea. Mild to moderate nausea and vomiting occurred in 66% of patient trials in which no pretreatment antiemetics were administered. Other toxicities included phlebitis from 5-FU in 71%, skin toxicity in 11%, mild alopecia in 25%, and fatigue in 54% of patients. Nephrotoxicity (creatinine greater than 2.0 mg/dL) occurred in one patient. The dose of carboplatin resulting in grade 2 toxicity was 180 mg/m2 in one patient, 240 mg/m2 in one, 300 mg/m2 in seven, 360 mg/m2 in ten, and 420 mg/m2 in one. Based on these results, we recommend a starting dose of carboplatin, 300 mg/m2, in combination with five days of continuous infusion 5-FU. In this dose and schedule, this combination was well tolerated and demonstrated antitumor activity in head and neck cancer. To confirm these promising results, a Southwest Oncology Group prospective randomized trial is in progress comparing carboplatin and 5-FU, cisplatin and 5-FU, and standard-dose weekly methotrexate in recurrent-disease patients.
Utility of routine endoscopy in the follow-up of resected gastric carcinoma
Authors: C. Villarreal-Garza, M. Rojas-Flores, A. Castro-Sanchez, E. Leon-Rodriguez
Journal: Journal of Clinical Oncology (2008)

4568 Background: Follow-up with routine endoscopy after resection of gastric carcinoma is frequently performed without definitive evidence of its impact in survival rate. Methods: To evaluate the usefulness of routine endoscopy for the follow-up of patients with history of surgically resected gastric carcinoma, we conducted a retrospective study of patients with gastric carcinoma diagnosed between 1980 and 2006, in whom routine endoscopy was performed after surgical resection with curative intention. Clinical data including site of recurrence, treatment and outcome were recorded. Results: Five hundred and twenty nine patients with the diagnosis of gastric cancer within the study period were found, of whom 312 (59%) were unresectable, 91 (17%) had palliative surgery, and 126 (24%) were the study group. Four hundred and twenty seven endoscopies were performed in total. The average number of endoscopies per patient was 3.3, and mean time between endoscopies was 10.4 months. Of the 126 resected cases, 74 (58.7%) developed a recurrence: 22 locoregional, 10 peritoneal, 28 metastatic disease, 4 local and peritoneal, and 10 local and metastatic. Routine endoscopy was able to detect asymptomatic isolated locoregional recurrence in 5 (6.7%) patients. In two, the recurrence was unresectable and the patients lived 2 and 28 months after recurrence. Re-resection with curative intention could only be performed in 3 patients, which represents 4.0% of patients with recurrence and 2.3% of all resected patients. Two are alive without evidence of disease 24 and 74 months after re-resection, and one patient died due to surgical complications. Seventeen out of the 22 locoregional recurrences were symptomatic (77.2%), and were not detected by routine endoscopies. In five cases (31%), a re-resection was possible, but only one patient is currently alive without disease 6 months after recurrence. Conclusions: In our experience, routine endoscopy has limited usefulness for the detection of resectable asymptomatic gastric cancer recurrences. The majority of recurrences are not detected by routine endoscopy, but present with symptoms that require further investigation. Randomized cost-efficiency studies are needed to confirm these findings. No significant financial relationships to disclose.
Pre- and postoperative inflammatory response to predict survival in patients undergoing potentially curative resection for colorectal cancer.
Authors: David G. Watt, Michelle Leana Ramanathan, James Hugh Park, Paul G. Horgan, Donald C. Mcmillan
Journal: Journal of Clinical Oncology (2015)

609 Background: It is now recognized that the presence of a pre-op systemic inflammatory response (SIR) is associated with poor long term outcomes independent of tumour stage. However, although the post-op SIR has been associated with poorer short term outcomes, such as development of infective complications including anastomotic leak, and these complications have been implicated in poorer long term outcome, it is not clear whether the postoperative SIR is independently associated with long term outcome. Therefore, the aim of the present study was to determine whether post-op CRP concentrations were independently associated with long term outcome following potentially curative surgery for colorectal cancer. Methods: Data from consecutive patients (n=800) undergoing potentially curative resection of colorectal cancer from a single institution (March 1999 to May 2013) were studied. The relationship between post-op CRP on days 2, 3, and 4 (using standard thresholds for infective complications: day 2 CRP &gt;190 mg/L, day 3 CRP &gt;170 mg/L and day 4 CRP &gt;145 mg/L) and cancer-specific survival (CSS) and overall survival (OS) was examined using Cox regression analysis. Results: The majority of patients were male (54%) and had node negative disease (61%). 26% received adjuvant therapy. Median follow up was 49 months with 169 cancer and 132 non-cancer deaths. On univariate survival analysis pre-op modified Glasgow Prognostic Score (mGPS) (HR 1.38, p=0.001), post-op day 2 CRP &gt;190 mg/L (HR 1.47, p=0.012) and post-op day 3 CRP &gt;170 mg/L (HR 1.46, p=0.018) were associated with CSS. On multivariate analysis both the mGPS (HR 1.20, p=0.080) and day 3 CRP &gt;170 mg/L (HR 1.41, p=0.032) were independently associated with CSS and both the mGPS (HR 1.27, p=0.003) and day 3 CRP &gt;170 mg/L (HR 1.32, p=0.027) were independently associated with OS. The post-op day 3 prognostic value was largely confined to the mGPS 0 group (HR 1.68, p=0.017 for CSS and HR 1.59, p=0.006 for OS). Conclusions: Both the pre- and post-op SIR were independently associated with long term survival following surgery for colorectal cancer. The SIR is a useful unifying concept, linking surgery and outcomes in patients with cancer.
Neoadjuvant oxaliplatin (OXA), raltitrexed (TOM), 5- fluorouracil (FU) and folinic acid (FA) + radiotherapy followed by optimal surgery in locally advanced rectal cancer (LARC)
Authors: A. Avallone, P. Delrio, E. Ravo, P. Marone, S. Lastoria, A. Petrillo, F. Tatangelo, A. Budillon, I. Carreca, P. Comella
Journal: Journal of Clinical Oncology (2004)

9624 Background: Preoperative chemoradiation in LARC may produce downstaging and downsizing of the tumor, increases the change of better local control and, in selected cases, sphincter sparing procedures.OXA displayed radiosensitizing properties and significantly enhanced the antitumour activity of TS inhibitor, FU and TOM. In a previous dose-finding study we showed that OXA (100 mg/mq) +TOM (2.5 mg/mq) + FU (900 mg/mq) + LFA (250 mg/mq) given concomitantly to radiotherapy is a feasible approach for LARC in a preoperative setting (Avallone ASCO 2003). Therefore, a phase II study was started to determine the activity of this treatment in newly diagnosed patients with EUS- and MRI-staged LARC. Methods: Eligible pts received three biweekly courses of OXA + TOM on day 1 and FU + LFA on day 2 in combination with pelvic RT (45 Gy, 1.8 Gy/fraction × 25 fractions). Chemotherapy was always admnistered prior to radiotherapy and toxicity was evaluated weekly with NCI-CTC version 2. Total Mesorectal Excision was planned 6–8 weeks after chemoradiation. EUS and MRI was repeated after chemoradiotherapy. Pts with cT4, pN+ and pathological +ve circumferential resection margin (CRM) also received 4 months of adjuvant FU/LFA. Results: 21 pts (F, 11; M, 10) were recruited. Median age was 60 years, with PS (ECOG) 0–1. Clinical staging revealed T4, N+ and clinical +ve CRM (≤ 5 mm by MRI), in 3, 16 (10 N1, 6 N2), and 15 pts respectively. So far, 18 pts are evaluable for EUS and MRI response, and 17 pts have proceeded to TME. Downsizing of the tumor was detected in all pts. At pathological evaluation, CRM > 2 mm occurred in all but one pt, 8 pts showed a complete response (TRG 1), 7 pts a downstaging (5 TRG 2, and 2 TRG 3), and 2 pts had no stage variation (1 TRG 3 and 1 TRG 4). Safety findings were consistent with those observed in phase I with incidence of hematological grade 4 in only 3 pts (neutropenia, 3 pts), and non-hematological grade 3 in 3 pts (diarrea, 2, and stomatitis,1). Conclusions:These preliminary results highlight the favorable safety profile and the efficacy of the combination. Updated results will be presented at the meeting. No significant financial relationships to disclose.