tbuckley/cabot-search huggingface dataset:
Safe Administration of the Measles Vaccine to Children Allergic to Eggs
Authors: John M. James, A. Wesley Burks, Paula K. Roberson, Hugh A. Sampson
Journal: New England Journal of Medicine (1995)

The safety of administering the combined measles–mumps–rubella (MMR) vaccine to patients who are allergic to eggs has been debated for decades because of concern about potential anaphylaxis, since the live attenuated virus used in the vaccine is grown in cultured chick-embryo fibroblasts.
Underestimation of Regional Myocardial Perfusion With Tc-99m Sestamibi Single-Day Rest–Stress SPECT
Authors: C Cittanti, D Mele, P Colamussi, M Giganti, E Ricci, A Dafermou, L Uccelli, A Piffanelli
Journal: Clinical Nuclear Medicine (2000)

Myocardial perfusion scintigraphy with a Tc-99m sestamibi single-day SPECT protocol is a widely used technique to examine patients with possible or known coronary artery disease. A 76-year-old man with a clinical history suggestive of ischemic heart disease underwent Tc-99m sestamibi myocardial SPECT imaging with a same-day rest and stress protocol after temporary discontinuation of his current therapy, which included calcium channel and beta blockers and nitrates. The scintigraphic pattern was consistent with an asymptomatic infarction of the posterolateral myocardial wall and periinfarct ischemia. One week later, the patient had a Tc-99m sestamibi myocardial SPECT study at rest without discontinuing therapy, and scintigraphic images showed normalization of the posterolateral wall perfusion defect. The angiographic study showed a 90% stenosis of the circumflex artery. This case suggests that, during a 1-day cardiac SPECT protocol, washout of therapeutic pharmaceuticals may be responsible for underestimation of myocardial rest perfusion in territory supplied by a coronary artery with a critical stenosis.
AB0102 Differential Effects of CD4+T Cells and CD8+T Cells on the Induction of Osteoclasts from Human Monocytes
Authors: M. Kondo, Y. Murakawa, T. Matsumura, M. Moriyama, Y. Sumita, N. Harashima, M. Harada
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Activated T cells express RANKL and have been considered to pomote osteoclast (OC) differentiation. Alternatively, activated T cells were suggested to suppress OC differentiation via the production of IL-4 and IL-10. Additionally, in a mouse model, activated T cells were reported to drive monocytes to differentiate into dendritic cells (DCs) through GM-CSF production. 1) <h3>Objectives</h3> In this study, we investigated effects of CD4+ T cells or CD8+ T cells with or without IL-2 on the induction of OC from human monocytes. <h3>Methods</h3> Monocytes, CD4+ T cells, and CD8+ T cells were prepared from PBMC of healthy volunteers. After incubation of monocytes with RANKL (50 ng/ml) and M-CSF (20 ng/ml) for 14 days, OC differentiation was evaluated by the TRAP staining. Additionally, we added CD4+T cells or CD8+T cells with or without IL-2 (20U/ml) at the initiation of the culture. <h3>Results</h3> Apparent OCs were induced from human monocytes by the culture with RANKL and M-CSF. The addition of CD8+ T cells facilitated the OC differentiation. Conversely, the addition of CD4+ T cells with IL-2 remarkably inhibited the OC differentiation, with preferential induction of DCs. <h3>Conclusions</h3> CD8+ T cells seem to facilitate OC differentiation from monocytes. Alternatively, irrespective of the presence of RANKL and M-CSF, CD4+ T cells with IL-2 facilitate DC differentiation, thereby resulting in drastic inhibition of OC differentiation. <h3>References</h3> Miyamoto T, Ohneda O, Arai F, Iwamoto K, Okada S, Takagi K, et al. Bifurcation of osteoclasts and dendritic cells from common progenitors. Blood. 2001,15;98(8):2544-54. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1416
OT1-01-02: A Multicentre Study Assessing 12-Weekly Intravenous Bisphosphonate Therapy in Women with Low Risk Bone Metastases from Breast Cancer – The TRIUMPH Trial.
Authors: N Bouganim, J Hilton, L Vandermeer, S Hopkins, P Spencer, D Robbins, E Amir, S Dent, C Milano, D Ooi, G Dranitsaris, M Clemons
Journal: Cancer Research (2011)

Abstract Background: Metastatic bone disease is a major cause of morbidity and mortality for breast cancer patients. Bisphosphonates (BP) have been shown to significantly delay the onset and frequency of skeletal related events (SREs), improve pain control and overall quality of life. Most patients receive intravenous BP every 3–4 weeks regardless of their individual risk for a SRE. This “one size fits all” strategy could expose those patients at a relatively low risk of SREs to an increased chance of adverse drug effects, as well as to the financial and quality of life burden of multiple visits to the cancer centre for treatments. This study aimed to assess whether IV BP can be safely given at reduced frequency. Methods: The primary objective of this study is to demonstrate in women with biochemically defined low-risk bone metastases that the administration of IV BP every 12 weeks is sufficient to maintain biochemical stability for one year. Eligibility criteria include; bone metastases from breast cancer, have received at least three months of regular 3–4 weekly IV BP, satisfactory renal function, adequate dental health, no systemic treatment change or recent SRE within 4 weeks of study entry. Low risk disease will be defined as serum CTx levels &amp;lt;600 ng/L Biochemical failure is defined as CTx levels &amp;gt;600 ng/L measured at predefined time points (6, 12, 24, 36 and 48th). Secondary objectives are to evaluate the palliative benefit of 12-weekly IV BP therapy as reflected by occurrence of SREs, analgesic use, self-reported pain using the validated BP and FACT-BP questionnaires. Sample size was calculated at 68 patients. Given the small sample size, nonparametric Bootstrapping will be employed to calculate point estimates, standard deviations and 95% confidence intervals (CIs). An exploratory multivariable analysis will also be undertaken to determine baseline factors that were associated with patient's maintaining their telopeptide levels in the low risk range. Conclusion: TRIUMPH opened in October 2010 and as of June 2011, has quickly accrued 54/68 patients (79%). This trial has the potential to allow lower risk women to receive less frequent dosing of bisphosphonates, thus improving their quality of life with less cancer center visits and reducing their chance of drug induced adverse events. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-01-02.
Abstract 3142: Whole genome sequencing of oligodendrogliomas identifies genes mutated at a low frequency that contribute to tumor formation.
Authors: Lale Erdem-Eraslan, Maurice de Wit, Daphne Heijsman, Andreas Kremer, Peter J. van der Spek, Peter A.E. Sillevis Smitt, Pim J. French
Journal: Cancer Research (2013)

Abstract Background: Causal genetic changes in oligodendrogliomas (OD) with 1p/19q codeletion include mutations in IDH1, IDH2, CIC and FUBP1. Here, we have performed whole genome sequencing on three ODs to determine whether additional genetic changes contribute to tumor formation. Methods: We performed whole genome sequencing of DNA from 3 ODs grade III with 1p/19q codeletion and matched germline DNA. Targeted resequencing of identified genes was performed in an additional 32 ODs with 1p19q LOH (28/32) or partial loss of 1p (2/32), 19q (2/32). All mutations were validated by Sanger sequencing. Constructs of wildtype and mutated genes were subsequently generated (n=13), fused to GFP for visualization. Established cell lines were created to perform functional analysis. Results: Whole genome sequencing identified a total of 55 mutations in coding exons (range 8-32 mutations per tumor), including the known molecular abnormalities in IDH1 (2/3), IDH2 (1/3), CIC (2/3) and FUBP1 (1/3). Mutations in the ATRX gene were not identified. In addition to these known genes, we identified mutations in additional genes, most of which were previously not implicated in ODs. We first examined the mutation frequency of these genes in an additional 32 tumors. No additional mutations were identified. We then performed functional analysis on a subset of these mutations. For ZNF238, we observed a difference in the sub cellular localization between wildtype and mutant contructs; the wildtype protein localized to the nucleus while the mutant protein is present in the cytoplasm. In addition, stably transfected ZNF238 mutant cell line shows increased proliferation compared to wildtype. Conclusion: Our results confirm that mutations in IDH, CIC and FUBP1 are present at high frequency in oligodendrogliomas with 1p/19q loss. Functional analysis of infrequently mutated genes provide evidence that they contribute to oncogenesis. Citation Format: Lale Erdem-Eraslan, Maurice de Wit, Daphne Heijsman, Andreas Kremer, Peter J. van der Spek, Peter A.E. Sillevis Smitt, Pim J. French. Whole genome sequencing of oligodendrogliomas identifies genes mutated at a low frequency that contribute to tumor formation. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3142. doi:10.1158/1538-7445.AM2013-3142
Gene Transfer Study Under Way
Authors: F. Antoine
Journal: JNCI Journal of the National Cancer Institute (1989)

Gene Transfer Study Under Way Get access Florence Antoine Florence Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 12, 21 June 1989, Pages 896–897, https://doi.org/10.1093/jnci/81.12.896 Published: 21 June 1989
AB0765 Treat to Target Strategy in Active Early Psoriatic Arthritis (Preliminary Results Of An Ongoing Remarca Study): Table 1
Authors: T.V. Korotaeva, E. Loginova, A. Glazkov, D. Karateev, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Treat to target (T2T) strategy for spondyloarthritis, including psoriatic arthritis (PsA) has been recently proposed. The main goal of this strategy is to reach remission or low/minimal disease activity (MDA). <h3>Objectives</h3> to investigate T2T strategy with methotrexate (MTX) subcutaneous (s/c) and anti-TNF-therapy (adalimumab) in active early peripheral psoriatic arthritis (EPsA). <h3>Methods</h3> 23 (M/F – 8/15) treatment-naïve patients (pts) with active peripheral EPsA, according to the CASPAR criteria, mean age 39.1±10.6 yrs., PsA duration 7 [4; 24] mo., disease activity index (DAS) 3.97 [3.07; 4.67], DAS28 4.33 [3.68; 4.73], Psoriasis duration 36 [12; 84] mo., PASI 6 [3.1;9.7], BSA (%) 1 [0.5; 3.65], HAQ 0.75 [0.63; 1.25], C-reactive protein (C-RP, mg/l) 15 [8.6;25.1], ESR (mm/h) 15 [8.6;25.1] were included. At the baseline and every other 3 mo. of therapy all pts underwent standard clinical examination: Tender Joint count (TJC78/28), Swollen Joint Count (SJC76/28), patient pain VAS, patient/physician9s global disease activity VAS, PASI, BSA, HAQ, DAS, DAS28, C-RP (mg/l), ESR (mm/h). Response to the treatment was defined as percentage of pts who met remission (DAS&lt;1.6 or DAS28&lt;2.6), low disease activity (LDA) (1.6≤DAS&lt;2.4 or 2.6≤DAS28&lt;3.2), MDA, ACR20/50/70. The dose of MTX (s/c) was escalated by 5 mg eow from 10 mg/wk to 20 mg/wk. If pts do not achieve the MDA/LDA or remission after 3 mo. MTX mono-therapy (MoT) combination therapy (CoT) MT+Adalimumab (ADA) 40 mg s/c eow will start. Mean ± SD, Me [Q25; Q75], χ<sup>2</sup>-test, Friedman ANOVA were performed. All p&lt;0.05 were considered to indicate statistical significance. <h3>Results</h3> Significant changes in baseline data up to 6 mo. of therapy are now avalible. <i>After 3 mo.</i> of therapy MoT MTX remission by DAS/DAS28 was seen in 13%/22.7%, LDA by DAS/DAS28 in 21.7%/27.3% and MDA in 26.1% of pts. ACR 20/50/70 was achieved 65.2%/26.15/8.7% of pts accordingly. After 3 mo. 4 pts had high disease activity and were treated by CoT MT+ADA 40 mg s/c eow, 19 pts were continued MTX MoT. <i>After 6 mo.</i> remission by DAS/DAS28 was seen in 34.8%/39.1%, LDA by DAS/DAS28 in 26.1%/39.1% and MDA in 47.8% of pts. ACR 20/50/70 was achieved 73.9%/60.9%/47.8% of pts accordingly. After 6 mo. of MTX MoT (n=19) remission by DAS/DAS28 was seen in 36.8%/36.8%, LDA in 15.8%/36.8%, MDA in 47.4% of pts. ACR 20/50/70 was achieved 68.4%/52.6/42.1% of pts. MTX+ADA CoT (n=4) ACR 20/50/70 and MDA was achieved 100%/100%/75% and 50% of pts accordingly. <h3>Conclusions</h3> T2T strategy - active treatment of EpsA pts with predominantly MoT MTX s/c for 6 mo. show MDA in a half of pts (47.8%), remission by DAS in a third (34.8%) and ACR20/50/70 achieved 73.9%/60.9%/47.8% of pts accordingly. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3151
PM-20 * COMPARATIVE PROTEOME PROFILING OF IN VIVO AND IN VITRO MODELS OF DIPG
Authors: M. Stampar, S. Yadavilli, K. J. Brown, E. H. Raabe, K. E. Warren, M. Kambhampati, R. J. Packer, J. Nazarian
Journal: Neuro-Oncology (2014)

BACKGROUND: Diffuse intrinsic pontine glioma is one of the least understood pediatric tumors. We have recently identified two molecular subtypes of DIPGs (sonic hedgehog and N-Myc). Despite the existence of in vitro and in vivo models of the disease, molecular characterization of these models and their proximity to representing the disease has not been established. Here, we have done comparative protein profiling of a number of DIPG primary cells as well as protein profiles of a single specimen and specimens derived from its' in vivo and in vitro models. METHODS: Human primary DIPG (n = 4) and normal human cells derived from hindbrain (n = 2) were processed for protein profiling. Total protein was extracted and analyzed using SDS PAGE, and analyzed using Q Exactive mass spectrometer (ThermoFisher, CA, USA). Data and pathway analysis were done using the SequestHT and Ingeniuty Pathway Analysis software respectively. Protein was also extracted from a single human DIPG specimen, and its' in vitro and in vivo derived cells. Protein profiling of this specimens was performed as described above. RESULTS: In this study, we first investigated the protein profiles of four widely used DIPG primary lines, all H3.3K27M mutant. We show the overlap of the protein profile of these cells with established human DIPG subtypes. We further investigated the protein profile of a single DIPG tissue to its in vitro and in vivo models. We describe the fidelity of each model with respect to the molecular entity of the original tumor. The largest number of proteins were shared between primary tumor and murine model (846 proteins, 44%), where the primary tumor and cultured cells shared 30% (721) proteins. CONCLUSIONS: Established human DIPG cells represent tumor biology at the protein level. However, differences in molecular pathway of in vitro and in vivo models representing the disease exist.
OP0160 Evaluation of Non-Invasive Tests as an Early Diagnostic Screen for Pulmonary Arterial Hypertension in Patients with Systemic Sclerosis
Authors: H. Gladue, V. Steen, Y. Allanore, P. Maranian, D. Khanna
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Pulmonary arterial hypertension (PAH) affects 5-15% of all systemic sclerosis (SSc) patients and is associated with up to 30% mortality at 3 years. Early diagnosis improves the outcomes of PAH. We examined two cohorts: (1) The Pulmonary Hypertension Assessment and Recognition Outcomes in Scleroderma (PHAROS); a prospective cohort of SSc patients at risk for PAH or with incident PAH (1-2) and (2) An inception Paris Cochin Rheumatology cohort evaluating SSc patients suspected of having PAH (3). <h3>Objectives</h3> To evaluate various routinely collected clinical parameters and determine the number of cases missed by a single parameter versus a combination of parameters as non-invasive diagnostic screen for PAH (WHO Group I) in SSc patients. <h3>Methods</h3> Non-invasive tests including,- patient characteristics, systolic pulmonary arterial pressure (sPAP) on echocardiogram (TTE), FVC%/DLCO% ratio, and DLCO% predicted were evaluated alone and in combination for their ability to diagnose PAH in SSc patients as compared to right heart catheterization (RHC), the gold standard for diagnosis. <h3>Results</h3> In the PHAROS cohort (N=206), 59 had PAH. In the Cochin cohort (N=141), 10 had PAH. Various sPAP cut-off’s resulted in missed cases of RHC PAH. By also including DLCO or FVC/DLCO ratio, 50%&gt;78% of patients with RHC PAH missed by TTE were captured by PFT. (Table) In a multivariant logistic regression model (PAH vs No-PH) of the combined data, sPAP&gt;40mmHg (OR 8.1 [95%CI 2.9,25.1]) was the only significant determinant after adjusting for age, gender, disease duration, FVC/DLCO≥ 1.6, anti-centromere antibody and anti-SCL-70 antibody. <h3>Conclusions</h3> Using two large scleroderma cohorts, a combination of TTE with PFT complement each other for diagnosis of PAH. PFT with DLCO should be performed to screen for PAH in SSc. <h3>References</h3> Hinchcliff, M., A. Fischer, et al. (2011). “Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS): baseline characteristics and description of study population.” J Rheumatol 38(10): 2172-2179. Bae, S., R. Saggar, et al. (2012). “Baseline characteristics and follow-up in patients with normal haemodynamics versus borderline mean pulmonary arterial pressure in systemic sclerosis: results from the PHAROS registry.” Ann Rheum Dis 71(8): 1335-1342. Avouac, J., P. Airo, et al. (2010). “Prevalence of pulmonary hypertension in systemic sclerosis in European Caucasians and metaanalysis of 5 studies.” J Rheumatol 37(11): 2290-2298 <h3>Disclosure of Interest</h3> None Declared
GM<sub>3</sub>(Hematoside) Sphingolipodystrophy
Authors: Stephen R. Max, Noel K. Maclaren, Roscoe O. Brady, Roy M. Bradley, Margaret B. Rennels, Junicki Tanaka, Julio H. Garcia, Marvin Cornblath
Journal: New England Journal of Medicine (1974)

To characterize further disorders involving storage of glycosphingolipids, we studied an infant who had poor physical and motor development, coarse facies, macroglossia, gingival hypertrophy, squat hands and feet, flexor contractures of the fingers, thickened, loose, hirsute skin, bilateral large inguinal hernias, an enlarged liver and spleen, and normal fundi. Shortly after birth the patient became limp and unresponsive, dying at 3 1/2 months of age. The accumulation of ganglioside GM3 (hematoside) was established by quantitative lipid analysis of fresh-frozen post-mortem samples of brain and liver. Higher ganglioside homologues were completely absent. This unusual ganglioside pattern suggests that the defect in GM3 (hematoside) sphingolipodystrophy is in ganglioside biosynthesis, in contrast to previously described sphingolipidoses, which are due to deficiencies of catabolic enzymes. (N Engl J Med 291:929–931, 1974)
A Prospective Study of Growth and Biomarkers of Exposure to Aflatoxin and Fumonisin during Early Childhood in Tanzania
Authors: Candida P. Shirima, Martin E. Kimanya, Michael N. Routledge, Chou Srey, Joyce L. Kinabo, Hans-Ulrich Humpf, Christopher P. Wild, Yu-Kang Tu, Yun Yun Gong
Journal: Environmental Health Perspectives (2014)

Background: Aflatoxin and fumonisin are toxic food contaminants. Knowledge about effects of their exposure and coexposure on child growth is inadequate.Objective: We investigated the association between child growth and aflatoxin and fumonisin exposure in Tanzania.Methods: A total of 166 children were recruited at 6–14 months of age and studied at recruitment, and at the 6th and 12th month following recruitment. Blood and urine samples were collected and analyzed for plasma aflatoxin–albumin adducts (AF-alb) using ELISA, and urinary fumonisin B1 (UFB1) using liquid chromatography–mass spectrometry, respectively. Anthropometric measurements were taken, and growth index z-scores were computed.Results: AF-alb geometric mean concentrations (95% CIs) were 4.7 (3.9, 5.6), 12.9 (9.9, 16.7), and 23.5 (19.9, 27.7) pg/mg albumin at recruitment, 6 months, and 12 months from recruitment, respectively. At these respective sampling times, geometric mean UFB1 concentrations (95% CI) were 313.9 (257.4, 382.9), 167.3 (135.4, 206.7), and 569.5 (464.5, 698.2) pg/mL urine, and the prevalence of stunted children was 44%, 55%, and 56%, respectively. UFB1 concentrations at recruitment were negatively associated with length-for-age z-scores (LAZ) at 6 months (p = 0.016) and at 12 months from recruitment (p = 0.014). The mean UFB1 of the three sampling times (at recruitment and at 6 and 12 months from recruitment) in each child was negatively associated with LAZ (p < 0.001) and length velocity (p = 0.004) at 12 months from recruitment. The negative association between AF-alb and child growth did not reach statistical significance.Conclusions: Exposure to fumonisin alone or coexposure with aflatoxins may contribute to child growth impairment.Citation: Shirima CP, Kimanya ME, Routledge MN, Srey C, Kinabo JL, Humpf HU, Wild CP, Tu YK, Gong YY. 2015. A prospective study of growth and biomarkers of exposure to aflatoxin and fumonisin during early childhood in Tanzania. Environ Health Perspect 123:173–178; http://dx.doi.org/10.1289/ehp.1408097
Natural History and Treated Course of Usual and Desquamative Interstitial Pneumonia
Authors: Charles B. Carrington, Edward A. Gaensler, Ronald E. Coutu, Muiris X. FitzGerald, Raj G. Gupta
Journal: New England Journal of Medicine (1978)

Patients with confirmed interstitial pneumonia were initially classified histologically into "desquamative" (n = 40) and "usual" (n = 53) types, and followed for one to 22 years. Both the diagnosis and the extent of fibrosis affected the course and response to therapy. Mortality in desquamative interstitial pneumonia was 27.5 per cent, and mean survival 12.2 years, as compared with 66.0 per cent and 5.6 years in usual interstitial pneumonia (P less than 0.01). Without treatment, 21.9 per cent with the desquamative but none with the usual type improved. With corticosteroid therapy, 61.5 per cent with desquamative and only 11.5 per cent with usual interstitial pneumonia improved, whereas 27.0 per cent and 69.2 per cent worsened. We conclude that the histologic classification of chronic interstitial pneumonia used here permits forecasts of prognosis and response to treatment that cannot be deduced from other data.