tbuckley/cabot-search huggingface dataset:
SP0174 Co- or Multimorbidities. Growing Older with an Rmd
Authors: T. Sokka-Isler
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> All other diseases that coexist with a disease of interest are called comorbidities. Comorbidities in inflammatory rheumatic diseases may be associated with persistent inflammatory activity or disease-related organ damage, or may be related to medications. Lifestyle choices such as smoking or physical inactivity contribute to comorbidity. Patients with rheumatic diseases meet health professionals regularly and are more often tested for osteoporosis or cholesterol levels than individuals without rheumatic disease, which may contribute to a higher prevalence of some comorbidities. Comorbidities can also be unrelated to rheumatic diseases or their treatments. Poor physical function and low muscle strength are significant predictors of mortality in rheumatic diseases, other chronic diseases, ageing individuals, and the general population. Poor physical function predicts earlier mortality in diseased and normal populations at levels of significance similar to or greater than most known biomedical predictors such as laboratory tests. The data support recommendations for regular exercise in all individuals whether or not they have a disease, to promote health and longevity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6229
Abstract 2404: A DNA vaccine encoding the androgen receptor ligand binding domain elicits anti-tumor immune responses in vivo
Authors: Brian M. Olson, Laura E. Johnson, Douglas G. McNeel
Journal: Cancer Research (2010)

Abstract The androgen receptor (AR) is a nuclear receptor that plays a critical role in both androgen-dependent and -independent prostate cancer, and remains the primary target of therapy for metastatic prostate cancer. We have shown that the AR may be a potential immunological target antigen, identifying some prostate cancer patients that have concurrent antibody and cellular immune responses specific for the AR ligand-binding domain (LBD). We have also identified that some patients have cytotoxic T lymphocytes (CTL) that are specific for ARLBD-derived HLA-A2 epitopes, some of which can lyse prostate tumor cell lines. Moreover, we demonstrated that these epitope-specific CTL could be elicited in HLA-A2 transgenic mice by means of a DNA vaccine encoding the ARLBD (pTVG-AR). In this report, we sought to evaluate whether this DNA vaccine could elicit anti-prostate tumor responses in relevant rodent models in which the ARLBD is expressed as a “self” antigen. First, Copenhagen rats immunized with the pTVG-AR vaccine four to six times at 14-day intervals were challenged with a syngeneic prostate tumor cell line subcutaneously implanted. These animals were found to develop T-cell responses specific for the ARLBD and have a significant delay in tumor growth compared with control vaccinated animals (p=0.018). In a separate autochthonous model, HLA-A2 transgenic mice were crossed with TRAMP mice and the resulting transgenic hybrid (A2/TRAMP) expressed HLA-A2 and developed prostate tumors driven by the SV40 large T antigen under a prostate-specific promoter. A2/TRAMP mice were similarly immunized with pTVG-AR, or control vector, at 14-day intervals and evaluated at 16 weeks of age. Mice immunized with pTVG-AR were found to develop HLA-A2 epitope-specific CD8+ T cell responses, and had fewer well-differentiated adenocarcinomas compared with control immunized mice. Finally, A2/TRAMP mice were immunized repetitively over time and followed for survival. Mice immunized with pTVG-AR (n=8) had a median survival of 218 days, compared with a median survival of 198 days for control (n=7) immunized animals (p=0.040, log-rank test). These combined data show that not only can the ARLBD be safely targeted in vivo (none of the immunized animals had any sign of autoimmunity or overt toxicity), but more significantly that vaccines targeting the ARLBD can elicit an anti-prostate tumor responses in separate animal models. These findings suggest that the ARLBD is a potentially attractive immunological target antigen for the treatment of human prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2404.
AB0640 Bone Mineral Density in Patients with Systemic Sclerosis
Authors: R. Alekperov, A. Smirnov, N. Toroptsova, E. Cheremukhina
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Studies of bone mineral density (BMD) in patients with systemic sclerosis (SSc) showed its decreasing in comparison with healthy control. Prevalence of low bone mass and severity of BMD decreasing differ significantly between patients from different countries and vary from 17% in China (Mok CC, et al. 2012) to 77% in Spain (Rios-Fernández R, et al, 2012). <h3>Objectives</h3> To assess BMD and frequency of osteoporosis (OP) in patients with SSc in Russia. <h3>Methods</h3> In case-control study BMD was evaluated in 52 postmenopausal women with SSc (16 – diffuse and 36 – limited form), mean age 57,6±7,1yrs and mean disease duration 11±8 yrs. Forty four healthy postmenopausal women (mean age 59,2±6,6yrs) served as control. BMD was measured at the lumbar spine (LS), femoral neck (FN) and total hip (TH) by DXA (Hologic 4500A). BMD decreasing grade was determined in according to WHO criteria <h3>Results</h3> BMD was significantly decreased in SSc women in comparison with control group: in LS – 0,804±0,090 vs 0,861±0,092 g/sm<sup>2</sup> (p=0,025); in FN – 0,670±0,128 vs 0,736±0,112 g/sm<sup>2</sup> (p=0,037), and in TH – 0,801±0,160 vs 0,884±0,124 g/sm<sup>2</sup> (p=0,03). Frequency of OP in SSc group was significantly more often than in control group (59% vs 11%, p&lt;0,0001). BMD didn9t differ between pts with diffuse or limited SSc. Decreasing of BMD in LS, FN and TH associated with age (r=-0,40, p&lt;0,001; r=-0,48, p&lt;0,001; r=-0,38, p=0,002, respectively), duration of postmenopausal period (r=-0,44, p&lt;0,001; r=-0,42, p&lt;0,001; r=-0,33, p=0,016, respectively), duration of SSc (r=-0,21, p=0,033; r=–0,37, p=0,001; r=-0,36, p=0,004, respectively) and hsCRP level (r=-0,22, p=0,041; r=-0,26, p=0,045; r=-0,35, p=0,011). BMD of FN and TH correlated also with daily dose of glucocorticoids (GC) (r=-0,34, p=0,025; r=-0,37, p=0,023, respectively). T-score was significantly lower in pts treated with GC than in GC free pts in LS (-2,01±1,52 vs -1,17±1,42, p=0,012), FN (-2,38±1,18 vs -1,26±1,25, p=0,003) and TH (-1,98±1,34 vs -0,84±1,19, p=0,011) <h3>Conclusions</h3> OP occurs in more than half cases of SSc pts. Low BMD in SSc pts apart from traditional risk factors of OP is associated with disease duration and inflammatory activity. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5426
Imaging of Hand-Schüller-Christian Syndrome by a Monoclonal Antibody
Authors: A P Jekunen, K J Kairemo, T Paavonen
Journal: Clinical Nuclear Medicine (1997)

Purpose Multifocal eosinophilic granuloma (Hand-Schüller-Christian syndrome) consists of localized lesions of histocytosis X originating from proliferating Langerhans' cells involving male children and young adults. Materials The authors present the first case of multifocal eosinophilic granuloma that was imaged by Tc-99m monoclonal antibody BW250/183 recognizing NCA-95 antigen on granulocytes. A 30-year-old man had a diagnosis of histiocytosis X for 16 years. Results All active known lesions were visualized. The previous radiotherapy fields were also accurately demonstrated as areas with no antibody accumulation. Bone marrow biopsy taken 30 hours after injection showed no infiltrations, but mild hypoplasia suggesting chronic disease was demonstrated. Retrospectively, the authors performed digital autoradiography from tissue samples and found specific targeting with the same BW250/183 antibody. Conclusion Their results indicate that antibody targeting is possible in multifocal eosinophilic granuloma, probably even allowing radioimmunotherapy.
Open-label, multicenter, phase II trial of ABI-007 in previously treated and previously untreated patients with metastatic malignant melanoma
Authors: E. M. Hersh, S. O’Day, R. Gonzalez, W. E. Samlowski, M. S. Gordon, M. J. Hawkins
Journal: Journal of Clinical Oncology (2005)

7558 Background: ABI-007 (Abraxane TM), is an albumin-bound, nanoparticle form of paclitaxel with an improved therapeutic index that may be related to biological interactions with endogenous albumin receptors (eg, gp60) and binding proteins (eg, SPARC). The albumin-binding protein SPARC (osteonectin) was overexpressed in primary and metastatic malignant melanomas but not in normal melanocytes (Ledda et al, J Invest Derm 108:210, 1997) and was a predictor of clinical outcome in thin melanomas (Massi et al, Human Path 30:339, 1999). Methods: We conducted a Phase II study of ABX administered weekly for 3 weeks q4w without premedication in chemotherapy-naive (CN) (150 mg/m2) and previously treated (PT) (100 mg/m2) patients (pts) with measurable metastatic malignant melanoma (MMM). Results: 13 CN and 36 PT pts have been enrolled; 11 CN and 13 PT pts are currently evaluable for toxicity and response. Median age was 59 (range, 32–79); median number of metastatic sites was 2 (range, 1–8); median ECOG PS was 0 (range, 0–1). 8 CN and 12 PT pts had visceral involvement. The median number of monthly cycles received was 4 (range, 2–6) for CN pts and 4 (range, 1–6) for PT pts. 9 CN and 25 PT pts are continuing treatment. 84% (CN) and 92% (PT) of cycles were given without dose modification. No treatment-related (TR) deaths or TR grade (G) 4 toxicities occurred; no cases of febrile neutropenia were reported. TR G3 toxicities included fatigue (13%); neutropenia (13%); leukopenia (8%); rash (8%); alopecia, anemia, infection, lymphedema, motor neuropathy, and tumor pain (4% each). 3 CN and 9 PT pts have progressive disease. 2 CN pts have achieved a partial response; 1 additional CN and 4 PT pts with stable disease have continued on ABX without progression for >/= 24 weeks. Conclusions: ABX was well tolerated and resulted in long-term disease control in patients with MMM, some of whom had rapidly progressive disease while on previous therapy. Final study results will be presented. However, based on these encouraging early results in pts with aggressive visceral disease, further studies with ABX in MMM are being considered. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration American BioScience American BioScience
Abstract 523: Three-dimensional hyaluronic acid-based hydrogel systems for studies of cancer invasion
Authors: Lisa A. Gurski, Ngoc T. Nguyen, Kenneth C. van Golen, Xinqiao Jia, Mary C. Farach-Carson
Journal: Cancer Research (2010)

Abstract Currently available invasion assays for study of cancer metastasis have limitations that led us to develop a novel system that provides a more flexible, quantifiable, and physiologically relevant method to study cancer cell invasion. The three-dimensional (3D) hyaluronic acid (HA) hydrogel invasion assay then was used to study HA receptor signaling as it occurs during prostate cancer metastasis to bone marrow. Our invasion assay uses the HA hydrogel which reflects the prevalence of HA in the bone marrow and its key role in the promotion of cancer cell motility and tissue invasion. The HA hydrogel spontaneously crosslinks via interaction of aldehyde and hydrazide groups, allowing for direct encapsulation of cells within the gel. This cell/gel construct is plated in a 12 mm tissue culture insert for construction of the invasion assay. The cells are situated on a single plane so that individual cell movement from that plane can be tracked. We show that our 3D HA hydrogel invasion assay allows for cell migration/invasion in response to a chemoattractant, fetal bovine serum (FBS), and that this movement is easily quantified using confocal microscopy techniques over a distance of up to 1 mm. The ability of cancer cells to invade the HA hydrogel depends on their expression of HA receptors and hyaluronidases; more highly invasive cell lines express HA receptors and hyaluronidases at higher levels. We will show that culture in the HA hydrogel triggers differential expression and/or compartmental translocation of HA receptor proteins and downstream effectors, all of which contribute to motility and metastasis. Ongoing work examines the role that a specific HA receptor, RHAMM, plays in prostate cancer metastasis, specifically how it activates Rho GTPases that increase cell motility. We will show how these physiologically relevant 3-D HA hydrogel invasion assays can be used to study such pathways. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 523.
Possible Graft-versus-Host Reaction after Intrauterine Transfusion for Rh Erythroblastosis Fetalis
Authors: J. Lawrence Naiman, Hope H. Punnett, Harold W. Lischner, Marie L. Destiné, James B. Arey
Journal: New England Journal of Medicine (1969)

An illness characterized by jaundice, aplastic anemia and striking histiocytic reaction in the bone marrow developed in an eight-week-old infant who survived three intrauterine transfusions for Rh erythroblastosis fetalis. Culture of peripheral blood lymphocytes suggested two populations of lymphocytes based on differences in Y-chromosome length. One of these resembled that of one of the donors of the intrauterine blood transfusions. In spite of initial hematologic improvement the infant's condition deteriorated, with multiple infections and progressive weight loss until death at 13 weeks of age. Although lymphoid and thymic atrophy were evident at autopsy these changes were considered to reflect atrophy (secondary to a graft-versus-host reaction) rather than primary immunologic deficiency disease. This observation supports recommendations of others that blood intended for transfusion to the fetus be first rendered free of viable lymphocytes.
SAT0176 Smoking increases systemic lupus erythematosus susceptibility in women carrying the HLA-DRB1 risk alleles
Authors: S.-Y. Bang, J.-S. Lee, Y.-B. Joo, J.-J. Kim, C.-N. Son, K.-H. Jung, H.-S. Lee, S.-C. Bae
Journal: Annals of the Rheumatic Diseases (2013)

Summary: This case report demonstrates a rare vascular pattern of a left external carotid artery (ECA) that arises directly from the aortic arch (AA), along with a type II proatlantal-vertebral artery anastomosis. Our research shows no report of an ECA arising from the AA. This, in association with a type II proatlantal anastomosis, is interesting because of its apparent rarity.
Abstract 647: TTAC-0001, anti-VEGFR2/KDR monoclonal antibody, inhibits VEGFR signaling and tumor growth in preclinical models
Authors: Younggeon Jin, Juyoun Jin, Heekyoung Yang, Minjae Park, Weon Sup Lee, Sung-Woo Kim, Sang Ryeol Shim, Yeonjoo Kim, Sang Hoon Lee, Jin-San Yoo, Ho Jun Seol, Do-Hyun Nam
Journal: Cancer Research (2011)

Abstract Tumor angiogenesis is the process that leads to the formation of blood vessels in a tumor and a prognostic indicator in various cancers. Vascular endothelial growth factor (VEGF) and its receptors are considered to be primary regulators of tumor-induced angiogenesis and activation of VEGFR2/KDR is the major signaling pathway for tumor growth. In addition, VEGFR2/KDR is also expressed in many cancer cells, and regulates cell growth and survival through autocrine pathway. In this study, we evaluated the therapeutic potential of TTAC-0001, fully human antibody against VEGFR2/KDR, for the inhibition of tumor growth. In the tube formation assay using HUVEC, TTAC-0001 exhibited a potent anti-angiogenic activity in vitro. In U-87 MG glioblastoma cells, TTAC-0001 significantly inhibited the phosphorylation of VEGFR2/KDR mediated by VEGF. To reveal in vivo efficacy, we have tested TTAC-0001 in glioblastoma and colorectal xenograft models. We demonstrated that antitumor activity of TTAC-0001 in preclinical models correlated with induction of growth arrest and apoptosis as well as the inhibition of angiogenesis. Currently, we are evaluating the combination of TTAC-0001 with chemotherapeutic agents in xenograft models. A single dose study performed in mouse allowed us to establish the relationship between the pharmacokinetics (PK) and efficacy of TTAC-0001. Taken together, our data suggest that targeting VEGFR2 pathway by TTAC-0001 would be a promising candidate for the treatment of cancer. (This study was supported by grants of the Korea Healthcare technology R&amp;D Project, Ministry for Health &amp; Welfare Affairs (A092255 and A040016) and Advanced Medi-cluster R&amp;D Project, DaejeonTechnoPark, Republic of Korea. Seol HJ and Nam DH are co-corresponding authors for this manuscript.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 647. doi:10.1158/1538-7445.AM2011-647
PWE-131 Does Capsule Endoscopy Have a Role in Patients with Chronic Liver Disease and Obscure Gastrointestinal Bleeding
Authors: P S Sidhu, M E McAlindon, R Sidhu
Journal: Gut (2013)

<h3>Introduction</h3> Chronic liver disease (CLD) is commonly associated with anaemia. Whilst varices represent the commonest cause of gastrointestinal bleeding in patients with CLD, in patients where iron deficiency anaemia (IDA) persist, capsule endoscopy (CE) may have a useful role to investigate the small bowel (SB). We conducted a study to evaluate the utility of CE in patients with CLD and obscure gastrointestinal bleeding (OGB) and their subsequent management consequences. <h3>Methods</h3> We retrospectively analysed our data set and isolated patients with OGB and CLD. Data collected included demographics, clinical indication (overt bleeding (OB) or IDA) the presence of co-morbidity, diagnostic yield (DY) and subsequent follow up. <h3>Results</h3> Of the 1324 patients investigated for OGB using CE, 3%(n = 41) had CLD. The mean age was 61 years (range = 26–88) with 59% males. The indications for CE was IDA in 66%(n = 27) and OB in the remaining 34%. All patients in this cohort had other significant co-morbidity in addition to CLD. Five patients were on non-steroidal anti-inflammatories whilst 2 patients were transfusion dependent. The DY (as defined by lesions responsible for OGB) identified on CE was 49%(n = 20).The commonest finding was SB ulcer and erosions 27%(n = 11) and SB angioectasia (AE) 24%(n = 10). Other findings included SB varices (2), blood without definite source (5), a tumour (metastatic renal tumour) and other miscellaneous lesions (4). In 13 patients (32%), lesions found were within the upper GI tract, which had been underestimated at the index gastroscopy. These included gastric antral vascular ectasia (3), varices (oesophageal and duodenal)(2), blood without definite source (5) and others lesions (erosions, ulcers, portal hypertension and polyps )(9). In 2 patients, colonic lesions were identified (erosions and AE). There was no significant difference in the DY between those with IDA and OB (p = 0.59) and between the sexes (p = 0.41). In our cohort, management was altered in 90%(n = 18) of those with a DY, in the form of further procedures (25%, n = 5) which included repeat OGD (2), colonoscopy (2), double balloon enteroscopy (1) and the patients with renal metastasis avoided surgery. 25%(n = 5) of patients within this cohort also received argon photocoagulation therapy. On logistic regression, factors that were associated with a subsequent change in management included previous transfusions (p = 0.04) and SB AE (p = 0.03). <h3>Conclusion</h3> CE is a useful tool for investigation of OGB in patients with chronic liver disease and persistent anaemia. Ulcers and AE were the commonest pathology seen in the SB in patients with CLD, in keeping with the published literature. CE is also useful to pick up pathology in the upper GI tract which may have been underestimated. <h3>Disclosure of Interest</h3> None Declared.
Stem Cells and Cardiovascular and Renal Disease
Authors: Volker Schächinger, Andreas M Zeiher
Journal: Journal of the American Society of Nephrology (2005)

The traditional view that organs have only limited regenerative capacity has been challenged in recent years as adult bone marrow stem cells as well circulating progenitor cells have been identified to retain the plasticity to participate in neovascularization, a process so far believed not to be possible after birth. An organ that is damaged by ischemia causes the release of cytokines; these act via the flowing blood and stimulate the bone marrow, which then mobilizes progenitor cells to the blood and directs them to adhere to and migrate into the damaged organ. Thus, these progenitor cells most likely constitute a natural repair mechanism that counteracts degenerative or aging processes. On the basis of encouraging experimental data, first clinical trials have been established to demonstrate the safety and the feasibility of progenitor cell therapy in case of peripheral artery disease or myocardial infarction. Trials investigating injection of bone marrow or circulating progenitor cells into the coronary artery after an acute myocardial infarction not only demonstrates safety of the procedure but also gave hints toward efficacy. Nevertheless, these findings have to be validated by subsequent larger, prospective, randomized, controlled trials. There are also potential topics in nephrology, where modification of progenitor cell activity might be of benefit, such as renal ischemic disease, glomerular disease, and renal transplant vasculopathy. Finding a way to integrate the principle of progenitor cell action into therapeutic efforts might provide a completely new therapeutic strategy that not only attempts to retard disease progression but furthermore targets to regenerate damaged organs.
Prophylactic Use of Implanted Cardiac Defibrillators in Patients at High Risk for Ventricular Arrhythmias after Coronary-Artery Bypass Graft Surgery
Authors: J. Thomas Bigger
Journal: New England Journal of Medicine (1997)

Patients with coronary heart disease, left ventricular dysfunction, and abnormalities on signal-averaged electrocardiograms have an increased risk of sudden death. We evaluated the effect on survival of the prophylactic implantation of cardioverter–defibrillators in such patients at the time of coronary-artery bypass surgery.
Case 44-1979
Authors: Richard C. Cabot, Robert E. Scully, James J. Galdabini, Betty U. McNeely, James R. Lehrich, George M. Kleinman, Robert B. Colvin
Journal: New England Journal of Medicine (1979)

Presentation of CaseA 59-year-old woman was admitted to the hospital because of fever and confusion.She was well until one month earlier, when an ear infection was treated with an antibiotic. One week before admission she had an upper-respiratory-tract infection with a "cold sore." Five days before entry a bitemporal headache and back pain developed. Two days later she became febrile. On the following day her daughter observed that she was confused and disoriented, speaking to persons who were not in the room and commenting on an odor of fish on her hands. One day before admission she was . . .
THE ROLE OF EPOXYEICOSATRIENOIC ACIDS IN REGULATING ENDOTHELIAL FUNCTION AND THE EFFECTS OF A NOVEL SOLUBLE EPOXIDE HYDROLASE INHIBITOR GSK2256294 IN HUMANS
Authors: Lucy Yang, Joseph Cheriyan, Aili Lazaar, Kaisa Maki-Petaja, Ian Wilkinson
Journal: Journal of the American College of Cardiology (2016)