tbuckley/cabot-search huggingface dataset:
Marrow Transplantation from Related Donors Other Than HLA-Identical Siblings
Authors: Patrick G. Beatty, Reginald A. Clift, Eric M. Mickelson, Brenda B. Nisperos, Nancy Flournoy, Paul J. Martin, Jean E. Sanders, Patricia Stewart, C. Dean Buckner, Rainer Storb, E. Donnall Thomas, John A. Hansen
Journal: New England Journal of Medicine (1985)

Marrow transplantation has generally been limited to patients with a sibling who is genotypically identical for HLA. In a study of the acceptable limits of HLA incompatibility, 105 consecutive patients with hematologic cancers who received marrow grafts from haploidentical donors (study group) were compared with 728 similar patients concurrently receiving grafts from HLA genotypically identical siblings (control group). The unshared haplotypes differed variably: 12 were phenotypically but not genotypically identical for HLA-A, HLA-B, and HLA-D; 63 differed at one locus (A, B, or D); 24 at two loci; and 6 at three. A higher proportion of study patients had delayed engraftment, granulocytopenia, or graft rejection. Acute graft versus host disease occurred earlier and with greater frequency in study patients. The risk of the disease did not correlate with disparity for Class I (A or B) versus Class II (D-region) loci. Thus, incompatibility for HLA has an important effect on the course after clinical marrow transplantation. In spite of these complications, there was no statistically significant difference in the survival of the study patients and control patients who received their transplants during remission. (N Engl J Med 1985; 313:765–71.)
AB0065 Adaptation of human monocytes and macrophages to hypoxia
Authors: M. Fangradt, T. Gaber, M. Hahne, C. Strehl, M. Jakstadt, P. Hoff, G.-R. Burmester, F. Buttgereit
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease of diarthrodial joints, characterized by infiltration of immune cells and local tissue hypoxia. Migrating monocytes and differentiated macrophages are forced to adapt their energy metabolism to hypoxia. Hypoxia-inducible factor (HIF)-1α is known to act as key regulator for the adaptation of migrating cells into hypoxic areas. <h3>Objectives</h3> The aim of this study was to investigate the mechanisms used by human monocytes and macrophages to adapt to hypoxia. <h3>Methods</h3> Isolated human CD14<sup>+</sup> monocytes were incubated for 5h under normoxic (18% O<sub>2</sub>) and hypoxic (&lt;1% O<sub>2</sub>) conditions with or without PMA stimulation, respectively. Using a Nuclear Extract Kit (Actife Motiv), nuclear and cytosolic fractions were prepared in order to detect HIF-1α and NFκB by immunoblot. For the experiments with macrophages, primary human monocytes were differentiated into monocyte derived macrophages (hMDM) using M-CSF. The effects of normoxia and hypoxia on gene expression were compared between monocytes and hMDMs using quantitative PCR. <h3>Results</h3> Monocytes stabilise HIF-1α under hypoxic conditions in a time dependent manner. Interestingly HIF-1α was detected exclusively in the cytoplasm, but not in the nucleus of unstimulated cells. PMA stimulation, however, resulted in the translocation of HIF-1α into the nucleus with PKC-a/b<sub>1</sub> being an essential regulator of this process. Also differentiation of monocytes into macrophages was found to be accompanied by the translocation of HIF-1α into the nucleus. In monocytes, hypoxia does induce the expression of glycolytic genes despite the absence of HIF-1α in the nucleus. NFκB1 turned out to be the transcription factor which mediates the regulatory effect under these conditions. <h3>Conclusions</h3> Monocytes migrate into inflamed and non-inflamed tissues where they differentiate into macrophages. During this differentiation processs, HIF-1α translocates from the cytoplasm (monocytes) into the nucleus (macrophages). Therefore, while in macrophages HIF-1α seems to serve as key regulator for the adaptation to hypoxia, this function is fulfilled by NFκB1 in monocytes. <h3>Disclosure of Interest</h3> None Declared
Abstract 4436: Biological evaluation of folate prodrugs with a highly toxic derivative of doxorubicin
Authors: Khalid Abu Ajaj, Naser El-Abadla, Pia Welker, Samar Azab, Reiner Zeisig, Iduna Fichtner, Felix Kratz
Journal: Cancer Research (2011)

Abstract Folic acid is itself not biologically active but it is essential for the proliferation of cells. Cellular uptake of folate in the body is primarily mediated by the folate receptor (FR), a membrane-bound protein for which three isomers have been identified. The isomer FR-α is highly over-expressed in many human tumors. Since FR-α has a high affinity for binding and transporting physiologic levels of folic acid into cells, coupling a drug through a cleavable linker to folic acid can yield a prodrug that can be delivered inside tumor cells. Many studies have focused on reducible or acid-sensitive based linkers that are cleaved in the endosomes and/or cytoplasm. For the development of new folate receptor-targeted prodrugs, the highly active doxorubicin derivative N-(5,5-diacetoxybut-1-yl)doxorubicin was chosen to avoid potential saturation of the folate receptor. This acyclic doxorubicin diacetate undergoes an ester-mediated hydrolysis producing 2-pyrrolinodoxorubicin that is 500-1000 times more active than doxorubicin. Two prodrugs were designed to contain an acid-sensitive hydrazone bond (1) or in addition a disulfide bond (2) in order to elucidate the importance of the pre-determined breaking point for their in vitro and in vivo activity. In a 24h MTT assay, 1 was 5-fold more active than 2 in folate-positive KB cells in the nanomolar range whereas no activity was observed in the folate-negative A549 lung cancer cells, an observation that correlated well with the uptake of 1 and 2 in fluorescence microscopy studies. In subsequent in vivo studies in the folate-positive KB model, 1 was as active as the free drug but significantly less toxic when dosed at twice the dose of the free drug whereas 2 showed no anticancer efficacy. As an explanation, we could show by HPLC that prodrug 2 that additionally contains a disulfide bond undergoes rapid disulfide exchange in murine and human plasma in the order of 40% after 5 h at 37°C in contrast to 1 which was essentially stable after a 5 h incubation. 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 4436. doi:10.1158/1538-7445.AM2011-4436
Why States Are So Miffed about Medicaid — Economics, Politics, and the “Woodwork Effect”
Authors: Benjamin D Sommers, Arnold M Epstein
Journal: New England Journal of Medicine (2011)

Although the Affordable Care Act requires the federal government to fund most of the cost of the 2014 Medicaid expansion, other features of the legislation render Medicaid a fiscal threat and administrative challenge for states whose budgets are already in dire straits.
Biomolecular Recognition: ssDNA-Functionalized Nanoceria: A Redox-Active Aptaswitch for Biomolecular Recognition (Adv. Healthcare Mater. 7/2016)
Authors: Gonca Bülbül, Akhtar Hayat, Silvana Andreescu
Journal: Advanced Healthcare Materials (2016)

The reversible assembly of single-stranded DNA aptamers on redox-active nanoceria particles, as presented by S. Andreescu and team on page 822, can be induced or resolved in response to a molecular target. Application of this mechanism for the design of a biomolecular aptaswitch for detection of ochratoxin A is demonstrated.
Diagnosis of Pulmonary Embolism with Magnetic Resonance Angiography
Authors: James F.M. Meaney, John G. Weg, Thomas L. Chenevert, David Stafford-Johnson, Brian H. Hamilton, Martin R. Prince
Journal: New England Journal of Medicine (1997)

Diagnosing pulmonary embolism may be difficult, because there is no reliable noninvasive imaging method. We compared a new noninvasive method, gadolinium-enhanced pulmonary magnetic resonance angiography, with standard pulmonary angiography for diagnosing pulmonary embolism.
Wearable Cardioverter-Defibrillator Therapy for the Prevention of Sudden Cardiac Death
Authors: Jonathan P. Piccini, Larry A. Allen, Peter J. Kudenchuk, Richard L. Page, Manesh R. Patel, Mintu P. Turakhia
Journal: Circulation (2016)

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional,
THU0125 A multi-center, double-dummy, double-blind study of subcutaneous (SC) abatacept (ABA) compared with intraveneous (IV) ABA in japanese rheumatoid arthritis patients with inadequate response to methotrexate
Authors: T. Matsubara, H. Inoue, M. Iwahashi, A. Yamazaki, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SC ABA formulation is under development as an additional treatment option for Japanese rheumatoid arthritis (RA) patients. <h3>Objectives</h3> To compare the efficacy and safety of SC and IV ABA in RA patients with inadequate response (IR) to methotrexate (MTX). <h3>Methods</h3> This was a 24 weeks, double-dummy. double-blind study in active RA with MTX-IR (≥10 swollen and ≥12 tender joints, CRP≥0.8mg/dL). Patients were randomized 1:1 to weekly SC (125mg) with additional IV loading (10mg/kg) on Day1, or IV (10mg/kg, Day 1, 15, 29, and every 4weeks thereafter) for 24 weeks, both with MTX (6-8mg/week). The primary endpoint was ACR20 response at 24 week. The key secondary efficacy endpoints were ACR50 and 70 response, HAQ-DI response (improvement from baseline of ≥0.3), and DAS28-CRP remission (of &lt;2.6) at 24 weeks. Efficacy and safety were assessed by intent to treat (ITT) population. <h3>Results</h3> A total of 118 patients (59 for each group) were randomized and treated. 57 (96.6%) of SC and 56 (94.9%) of IV completed 24 weeks double-blind period. Mean baseline characteristics were similar between groups. Mean age (±SD) was 55.6±12.9 years, disease duration was 6.4±8.3 years, swollen joints were 17.0±7.1, tender joints were 21.6±9.6, DAS28-CRP was 5.79±0.89, and MTX dose was 7.3±0.9 mg/week for entire population. At week 24, SC and IV ACR20 response were similar, 91.5% (54/59; 95% CI 81.3, 97.2) and 83.1% (49/59; 95% CI 71.0, 91.6), respectively. At week2, 12, 24, ACR20 of SC was 28.8%, 81.4%, 91.5% and IV was 22.0%, 79.7%, 83.1%. ACR50/70 responses over 24 weeks were also comparable between both groups (ACR50 of SC and IV were 66.1% and 62.7%, ACR70 were 37.3% and 30.5%). HAQ-DI response and DAS28-CRP remission of SC and IV were 69.5% and 50.8%, 50.9% and 40.4% respectively. Frequencies of AEs and serious AEs over 24 weeks were comparable between both groups (52.5% vs 59.3% and 6.8% vs 5.1%). Most common AEs were infections with mild or moderate in intensity (33.9% vs 49.2%). Local injection site reactions occurred in 3 patients (1 in SC and 2 in IV). All of them were mild or moderate. In total, anti-Ig and/or junction region antibody was detected in 1 of SC (1.7%) and anti-CTLA4 and possibly Ig antibody was detected in 1 of IV (1.7%). <h3>Conclusions</h3> In this study, SC shows comparable efficacy and safety to IV with low immunogenecitiy. SC will provide an additional treatment option for patients with RA. <h3>Disclosure of Interest</h3> None Declared
A7.12 Analysis of clinical and antidestructive effects of rituximab in rheumatoid arthritis: Preliminary data
Authors: AV Pivanova, GV Lukina, YaA Sigidin, AV Smirnov, KH Kuzikyants, AYu Kuznetsova, SI Gluκhova, EL Nasonov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objective</h3> To compare clinical and antidestructive effect of Rituximab (RTX) in patients with rheumatoid arthritis (RA). <h3>Material and methods</h3> Clinical and radiological study of 61 patients (pts) with RA (mean disease duration 10,1 ± 7.7 years, mean DAS28 6.3 ± 0.94, RF-positive 87%, ACCP-positive 93%) treated with RTX (1000 mg&nbsp;x&nbsp;2 or 500 mg&nbsp;x&nbsp;2). Clinical effect was assessed by EULAR criteria; radiological progression by SVH method. <h3>Results</h3> patients were treated by different doses of RTX (500 × 2 or 1000 × 2) had good response. Good clinical results were registered in 29.7% (remissions – 14.6%) after 48 week of receiving 2 courses of RTX; good and satisfactory results in 85.3%. Whole group achieved a significant slowing of radiological progression in joint damage. After 48 weeks of treatment progression of articular destruction was absent in all pts in clinical remission, in 83% of pts with low disease activity, and in 43% of pts with moderate activity. Narrowing of joint space was more pronounced than bone destruction – 32% and 25% respectively. Clinical and antidestructive effects often did not coincide. Noteworthy, RTX treatment slowed joint damage in 54% of pts without clinical improvement. There were no significant correlations between clinical outcomes and doses of RTX. The high-dose use of PTX (1000 vs 500 × 2 × 2) was associated with a significant slowing radiographic progression. <h3>Conclusion</h3> Clinical and antidestructive results did not always coincide which suggests different mechanisms of clinical and antidestructive effects of anti-B-cell therapy. The therapeutic effect of different doses of RTX was practically the same but the antidestructive effect of higher doses was significantly greater.
Abstract 2201: Involvement of somatic mutations in silencing cystatin E/M tumor suppressor gene in breast cancer
Authors: Natarajan Venkatesan, Shawnt P. Issakhanian, Charles G. Ginther, Dennis J. Slamon, Eri S. Srivatsan, Mysore S. Veena
Journal: Cancer Research (2011)

Abstract Cystatin E/M is a cysteine protease inhibitor that has a tumor suppressive function in various cancers. Although promoter methylation is implicated in breast cancer, we wanted to determine whether the gene is also inactivated by somatic mutations. Thus, we analyzed breast cancer tissues and cell lines for the expression of Cystatin E/M and its effect on cancer cell growth and proliferation. RNA expression was observed in 3 (BT20, MB231 and ZR75.1) of 10 breast cancer cell lines by microarray and RT/PCR; however, the protein was not detectable in any of these cell lines by Western blotting indicating RNA and/or protein stability as a possible mechanism. Ectopic expression of cystatin E/M in MB435 cells, a cell line that did not show the RNA or protein expression, resulted in the inhibition of cell proliferation as studied by MTT assay. Western blotting and immunofluorescence studies indicated a reduced expression of its substrate cathepsin L with the reexpression of cystatin E/M. Varying expression of cystatin E/M (absent to strong) was also seen in a cohort of 24 human breast tumors; 8 of these tumors showed increased cathepsin L levels compared to a normal breast specimen. A mutation of Q47 to a stop codon in exon1 was observed in 2 tumor samples. These studies indicate that cystatin E/M may be inactivated by somatic mutations and the protein mediates tumor suppression by regulating its substrate cathepsin L in breast cancer. 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 2201. doi:10.1158/1538-7445.AM2011-2201
Abstract 4153: Short term opioid receptor blockade inhibits cancer cell proliferation independent of immune function by upregulation of the OGF-OGFr axis: A tissue culture model of low dose naltrexone (LDN)
Authors: Renee N. Donahue, Patricia J. McLaughlin, Ian S. Zagon
Journal: Cancer Research (2010)

Abstract The opioid growth factor (OGF) is an autocrine produced and constitutively expressed peptide that interacts with the OGF receptor (OGFr) and subsequently targets the cyclin dependent kinase inhibitory (CKI) pathways to inhibit proliferation at the G1/S phase of the cell cycle. Naltrexone (NTX) is a nonselective opioid receptor antagonist that blocks this interaction. In vivo administration of a low dosage of NTX (LDN, 0.1 mg/kg) blocks opioid receptors for 4-6 h, resulting in a compensatory upregulation of OGF and OGFr. Following clearance of NTX, the elevated levels of OGF and OGFr interact to decrease cell proliferation. To investigate whether LDN inhibits cancer cell proliferation independent of immune function, a tissue culture model using short term NTX in human ovarian cancer cell lines (SKOV-3, OVCAR-3) was established. Cell replication and cell number were determined over 96 h in cultures treated with a single 6 h application of NTX (10−6 M). In SKOV-3 and OVCAR-3 cultures, cell number was decreased by 21-28% and 27-32%, respectively, between 48 and 96 h; DNA synthesis was inhibited ∼ 33% at 72 h. Peptide specificity studies using a variety of classical μ, δ, or κ opioid receptor agonists confirmed that only OGF inhibited cell number. Antibody neutralization of OGF in cultures revealed that endogenous OGF invoked the inhibitory growth effects of short term NTX. To evaluate which opioid receptor mediated the inhibitory action of short term NTX on growth, cultures were treated with siRNAs against the μ, δ, κ, and OGFr receptors; only OGFr was associated with short term NTX treatment. Immunocytochemical studies and semiquantitative analyses documented an upregulation of OGF and OGFr expression following short term NTX exposure in cancer cells; western blot analysis and receptor binding for OGFr revealed 2-fold increases of receptors 48 h after a brief exposure to NTX. NTX's inhibitory action was not related to apoptosis (TUNEL) or necrosis (trypan blue staining). To investigate whether short term NTX's action on cell proliferation was transduced by the p16 and/or p21 CKI pathways, siRNAs for p16 and p21 were utilized in combination with short term NTX. Silencing of p16 and/or p21 blocked the inhibitory action of short term NTX, indicating a mechanism directed toward the CKI pathways. Independent of immune function, short term opioid receptor antagonism has been demonstrated to inhibit cancer cell proliferation by upregulation of the OGF-OGFr axis. Upregulation of the OGF-OGFr axis by a brief opioid receptor blockade may provide a novel target for biotherapy of cancers. 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 4153.
AB0679 Analysis of disease activity, functional disability and articular damage in patients with juvenile idiopathic arthritis: a prospective outcome study.
Authors: D. Dop, C. E. Niculescu, D. Bulucea
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> JIA consists of a group of inflammatory processes characterised by chronic synovitis that occur before the age of 16 and are associated in variable proportions with various extra-joint manifestations. <h3>Objectives</h3> The <i>objective</i> of this study was to assess, for a period of 3 years, the evolution of the disease in relation to the characteristics of the onset of JIA, using the DAS28, CHAQ, JADI-A and JADI-E indices. <h3>Methods</h3> The study was prospective and it was carried out in the 2005-2010 period, on 3 groups of patients: 15 patients with systemic JIA, 15 patients with polyarticular JIA and 15 patients with oligoarticular JIA, for which we have assessed the clinical, laboratory and radiological factors at the onset of the disease. The patients were reevaluated after 3 years, following a special protocol that included the assessment of their general conditions, the degree of disease activity (DAS 28), articular impairment (according to the Dale score), radiological modifications, Steinbrocker classification, CHAQ, JADI-A, JADI–E. <h3>Results</h3> Disability was present in 53.33% of the patients (Steinbrocker stages II-IV); 20% presented a high level of disability – stages III-IV, with 2.22% of them being in stage IV. Radiological impairment was noticed in 19 patients (42.22%), the polyarticular form being the most affected – 10 cases (22.22%). 3 years after diagnosis, the CHAQ score has an average of 0.423, while DAS 28 has an average of 3.44; both values are better than the initial ones. The final DAS 28 values are higher in the female patients; this suggests that the female gender is an unfavorable prognostic factor. The articular damage pointed out by the JADI-A score was present in 15 patients (33.33%). Extra-articular damage was present in 24 patients (53.33%), the most affected form being the systemic one – 12 patients (80%). Remission was present in 13 patients (28.88%), 3 years after diagnosis. <h3>Conclusions</h3> Female gender, systemic form and the involvement of a large number of joints at the onset of the disease represent unfavorable prognosis factors. The DAS28 and CHAQ indices have shown improvements in comparison to the initial values, while the JADI-A and JADI-E damage indices, as well as the radiological score worsened. <h3>Disclosure of Interest</h3> None Declared
CARDIAC MR STRESS PERFUSION WITH REGADENOSON AND DOBUTAMINE IN CHILDREN: SINGLE CENTER EXPERIENCE IN REPAIRED AND UNREPAIRED CONGENITAL AND ACQUIRED HEART DISEASE
Authors: Cory Noel, Silvana Molossi, Ramkumar Krishnamurthy, Brady Moffett, Rajesh Krishnamurthy
Journal: Journal of the American College of Cardiology (2016)
Sociological Issues Influence European Cancer Programs
Authors: Kara Smigel
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Sociological Issues Influence European Cancer Programs Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 14, 17 July 1991, Pages 990–992, https://doi.org/10.1093/jnci/83.14.990 Published: 17 July 1991
NUANCES IN THE CLINICAL PRESENTATION OF ACUTE TYPE A AORTIC DISSECTION: AGE, GENDER, RACE, AND PRIOR CARDIAC SURGERY
Authors: Melanie Holtrop, Kevin Harris, Alan Braverman, Reed Pyeritz, Stuart Hutchison, Arturo Evangelista, Eduardo Bossone, Daniel Montgomery, Patrick O’Gara, Toru Suzuki, Kevin Greason, Linda Pape, Anil Bhan, Eric Isselbacher, Christoph Nienaber, Kim Eagle
Journal: Journal of the American College of Cardiology (2015)