tbuckley/cabot-search huggingface dataset:
AB0415 Impact of different clinical characteristics of rheumatoid arthritis (RA) on work activity of patients
Authors: O. Vakulenko, O.A. Krichevskaya, D.V. Goryachev, Sh.F. Erdes
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Work productivity loss and activity impairment is one of most important RA consequences and leads to considerable financial losses. <h3>Objectives</h3> To study the effect of RA clinical characteristics on work productivity of patients (pts). <h3>Methods</h3> 137 RA pts were enrolled: 116 women and 21 men. Average age was 52.03+13.17 yrs. Age at the onset of the disease was 42.12+14.43 yrs. 59 pts had paid employment. Joint damage was estimated according to Sharp Score in van der Heijde modification (total vdH-Sharp score) and RA activity – according to DAS28. Quantitative assessment of functional statute was done by using Health Assessment Questionnaire (HAQ). Study of work productivity and regular activities was done by questionnaire Work Productivity and Activity Impairment-Specific Health Problem Questionnaire (WPAI-SHP). Average value of DAS28 4.8+1.4, HAQ – 1.42+0.82, 60.6% were seropositive by RF, 79.6% - positive by ACCP. Median total vdH-Sharp score – 83.0[59.0-118.0]. 54.8% of pts at the moment of examination used methotrexate, 19.7% - biological agents, 8,8%&gt; leflunomide. <h3>Results</h3> Mean absenteeism was 28.2% (mediana 2.6%[0-44.4%]). In 28 out of 59 working pts the value were equal to 0. Mean presenteeism was 54.8%±34.4%. Regular activities determined in all pts was decreased by 53.6±25.7%. Association between clinical data and values of index WPAI was determined by using Spearman correlation factor. Absenteeism negatively correlated with RA duration (R=0.26). DAS28 index directly correlated to all WPAI indices: absenteeism – R=0.27; presenteeism – R=0.63; overall work impairment - R=0.46; activity impairment - R=0.52. Most strong correlation was found with pain intensity assessment by patient (by WAS), values of correlation were higher than 0.5. HAQ index was not connected with absenteeism while its association with presenteeism overall work impairment, activity impairment was high (R=0.64; R=0.40; R=0.61 correspondingly). Most expressed associations were determined between index of patient physical condition – PCS SF-36 as compared to mental. No correlation of WPAI with total vdH-Sharp score was found. <h3>Conclusions</h3> RA clinical characteristics strongly correlated to work productivity of pts determined by WPAI-SHP. RA severity determines dropping of absenteeism as well as presenteeism in RA pts. <h3>Disclosure of Interest</h3> None Declared
THE EFFECT OF CORONARY ARTERY DISEASE SEVERITY AND REVASCULARIZATION COMPLETENESS ON TWO YEARS CLINICAL OUTCOMES IN PATIENTS WITH SEVERE SYMPTOMATIC AORTIC STENOSIS UNDERGOING TRANSCATETHER AORTIC VALVE IMPLANTATION
Authors: Guy Vitberg, Emmanuel Harari, Ifat Lavi, Pablo Codner, Hana Vaknin-Assa, Abid Assali, Ran Kornowski
Journal: Journal of the American College of Cardiology (2015)
Combined blockade of the histamine H1 and H4 receptor suppresses peanut-induced intestinal anaphylaxis by regulating dendritic cell function
Authors: M. Wang, J. Han, J. Domenico, Y. S. Shin, Y. Jia, E. W. Gelfand
Journal: Allergy (2016)

Signaling through histamine receptors on dendritic cells (DCs) may be involved in the effector phase of peanut-induced intestinal anaphylaxis.The objective of this study was to determine the role of histamine H1 (H1R) and H4 receptors (H4R) in intestinal allergic responses in a model of peanut allergy.Balb/c mice were sensitized and challenged with peanut. During the challenge phase, mice were treated orally with the H1R antagonist, loratadine, and/or the H4R antagonist, JNJ7777120. Bone marrow-derived DCs (BMDCs) were adoptively transferred to nonsensitized WT mice. Symptoms, intestinal inflammation, and mesenteric lymph node and intestine mucosal DCs were assessed. Effects of the drugs on DC chemotaxis, calcium mobilization, and antigen-presenting cell function were measured.Treatment with loratadine or JNJ7777120 individually partially suppressed the development of diarrhea and intestinal inflammation and decreased the numbers of DCs in the mesenteric lymph nodes and lamina propria. Combined treatment with both drugs prevented the development of diarrhea and intestinal inflammation. In vitro, the combination suppressed DC antigen-presenting cell function to T helper cells and DC calcium mobilization and chemotaxis to histamine.Blockade of both H1R and H4R in the challenge phase had additive effects in preventing the intestinal consequences of peanut sensitization and challenge. These effects were mediated through the limitation of mesenteric lymph node and intestinal DC accumulation and function. Identification of this histamine H1R/H4R-DC-CD4+ T-cell axis provides new insights into the development of peanut-induced intestinal allergic responses and for prevention and treatment of peanut allergy.
PT-02 * LONG-TERM SURVIVAL (>20 YEARS) OF A CHILD WITH BRAINSTEM GLIOMA TREATED WITH ANTINEOPLASTONS A10 AND AS2-1: A CASE REPORT
Authors: G. Burzynski, T. Janicki, A. Marszalek, S. Burzynski
Journal: Neuro-Oncology (2014)

Tectal glioma is a subtype of midbrain brainstem glioma which occupies the tectum or quadrigeminal plates. The patient generally presents with symptoms related to increased intracranial pressure and requires treatment for hydrocephalus. No effective pharmacological treatments have yet been introduced. This report discusses a case of a 12-year-old male diagnosed with tectal glioma that had the onset of symptoms in November 1993. Initial treatment consisted of the placement of a ventriculoperitoneal shunt. After six years of stabilization of the disease, there had been an increase in the tumor size with signs of malignant transformation. In August 2001, he started treatment with Antineoplaston (ANP) A10 and AS2-1 infusions and continued for 20 months according to Phase II Protocol BT-09. The dosage of A10 was maintained between 12.5 and 14.7 g/kg/d and AS2-1 from 0.3 and 0.4 g/kg/d. He obtained a complete response and was switched to a maintenance study with A10 and AS2-1 capsules (0.26 g/kg/d of each), according to Protocol BT-34. All treatments were discontinued in December 2003. His condition continued to improve during the treatment with ANP and currently, 20 years from his diagnosis and over 12 years from treatment start, he is symptom free and leads a normal, productive life. This report indicates that it is possible to obtain long-term survival of a child with aggressive brainstem glioma with currently available investigational treatment.
Abstract 3326: BEZ235 enhances radiosensitization via blockade of PI3-kinase/mTOR pathway in cisplatin-selected non-small cell lung cancer stem cells
Authors: Kwang Woon Kim, Dae Kwang Jung, Bo Lu
Journal: Cancer Research (2010)

Abstract Purpose: Most drug resistance cancer cells have resisted to radiation therapy. In this study, we hypothesized that a dual inhibitor of PI3-kinase/ the downstream mammalian target of rapamycin (mTOR), BEZ235, could potentially enhance radiosensitization in cisplatin-selected non- small cell lung cancer stem cells. Methods: Clonogenic assay was used to determine radiosensitivity. Stem cell marker was detected with CD133 antibody. P-AKT, P-mTOR and P-S6R were detected by Western Blotting. Cell cycle was performed using flow cytometry. Autophagy was determined by punctuate localization of GFP-LC3 fusion protein, which observed under a confocal fluorescence microscope in vitro. Results: Basal CD133 which is a marker of stem cell, P-Akt, p-mTOR and P-S6R proteins were enhanced in cisplatin-selected non- small cell lung cancer stem cells (CSNSCLCSTC) when compared to parental non-small cell lung cancer (H460) cells. Cisplatin-selected non- small cell lung cancer stem cells mediate less radiation sensitivity when compared with parental cells in clonogenic assay(DER=0.82, p=0.02). However BEZ235 obviously enhanced sensitivity of cisplatin-selected non- small cell lung cancer stem cells to radiation (DER=1.2, p=0.01). Therefore, this enhanced radiosensitization was associated with a downregulation of PI3-kinase/mTOR signaling pathway and an increase in characteristic punctuate localization of GFP-LC3 as a marker for autophagy, suggesting that G2/M inhibition and autophagy were induced simultaneously. Conclusions: These findings may be utilized as a novel strategy to enhance radiation therapy in drug-selected non-small cell lung cancer stem cells showing radioresistance. 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 3326.
Abstract 31: Isoform level gene expression signature is a better discriminator of cancer from normal cells than gene level expression signature
Authors: ZhongFa Zhang, Ramana V. Davuluri
Journal: Cancer Research (2011)

Abstract The majority of mammalian genes generate multiple transcript variants and protein isoforms, which usually are differentially expressed in different cellular and disease conditions. We hypothesize that the isoform level gene expression profiles can better discriminate normal and cancer cells with different sub-types than gene-level expression profiles. We analyzed Affymetrix exon array data sets, collected from public domain (ENCODE and TCGA datasets from NCBI GEO database), comprising 160 cell lines of either normal or tumor tissues of origin. The unsupervised clustering of genome-wide gene expression estimates at isoform-level effectively grouped the normal and cancer cell lines with 97.5% homogeneity, regardless of the tissue origins of the cell lines, with only 4 exceptions out of 160 samples. However, at gene level, this homogeneity grouping rate was much lower, and was about 75% at best. The supervised method revealed genes and isoforms that are differentially expressed between pairs of tumor and normal samples, which can serve as signatures to effectively differentiate tumor and normal cell lines. Finally, the pathway analyses both at gene and isoforms-level indicate that there are subtle differences of derived pathways. The study reveals that there exists a common isoform-level signature that can be used not only for effective discrimination of oncogenic cell lines from non-oncogenic cell lines, but may also have important biological implications for a better understanding of common defining characteristics of tumors of varied types. Finally, we present the identified isoform-level gene signatures and associated pathways for melanoma, breast cancer and glioblastoma. 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 31. doi:10.1158/1538-7445.AM2011-31
FRI0037 Role of a transcription factor pu.1 in tgf-b signaling-mediated osteoclast differentiation
Authors: K. Ishiyama, N. Tamura, T. Yashiro, C. Nishiyama, K. Okumura, Y. Takasaki
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> TGF-βstimulation enhances the osteoclastgenesis, which is characteristiccally observed in inflamed joints of patients with rheumatoid arthritis. In some hematopoietic lineages including dendriticcells and T cells, TGF-βinduces PU.1 expression and subsequent its function. However, the relationship between PU.1 and TGF-βin osteoclastis largely unknown, even though PU.1 is known to be important for development of osteoclast. <h3>Objectives</h3> To examine the involvement of PU.1 in TGF-β-mediated osteoclastdifferentiation. <h3>Methods</h3> Osteoclasts were generated from whole mouse bone marrow cells by the cultivation with using macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor κB ligand (RANKL) for 3 days, and then adherent cells were further incubated with M-CSF and RANKL, in the presence or absence of TGF-β. To evaluate the effect of PU.1 in osteoclasts, PU.1 was knocked down using siRNAduring differentiation. Osteoclast formation was determined by TRAP staining, and the amount of mRNAs of the osteoclast marker genes was measured by quantitative real-time PCR. We analyzed the dynamics of PU.1 in TGF-β-mediated gene expression by using chromatin immunoprecipitation (ChIP) assay and Western blotting analysis. <h3>Results</h3> The number of TRAP-positive multinucleated cells and the mRNA expression levels of osteoclast-specific molecules including NFATc1 or cathepsin K (Ctsk) were significantly reduced in PU.1 siRNA-introduced cells. TGF-β stimulation increased the mRNA levels of the osteoclast markers and the number of TRAP-positive multinucleated cells. ChIP assay showed that PU.1 bound the promoter regions of osteoclast marker genes, such as Acp5 or Ctsk, and the amount of PU.1 on these promoters was higher in TGF-β-stimulated cells. When the effect of TGF-β on PU.1 protein level was analyzed by Western blotting, PU.1 protein levels in whole cell and cytosolic fraction were reduced by TGF-β stimulation, whereas PU.1 was not detected in nucleus. <h3>Conclusions</h3> TGF-βstimulation affects the expression and/or function of PU.1 in osteoclast-specific manner. <h3>References</h3> RongHuets: Mol. Cell. Biol, 2007, 27, 4018-4027. Leonhard X. Heinz ets: Blood, 2006, 107, 1445-1453. Goswami. R ets: J Immunol, 2012, 188, 968-975 <h3>Disclosure of Interest</h3> None Declared
SP0113 Primary SjöGren’s Syndrome: What is New in 2012 to 2013? (Win)
Authors: H. Bootsma
Journal: Annals of the Rheumatic Diseases (2013)

<h3></h3> The last year, significant progress has been made in the diagnostics, evaluation and treatment of primary Sjögren's syndrome (pSS). The progress in the various areas will be discussed in detail. With regard to diagnostics, preliminary American College of Rheumatology classification criteria (ACR) were introduced in 2012. These criteria fully rely on objective tests and do not make a difference between pSS and secondary SS (sSS). The preliminary ACR criteria will be discussed in relation to the widely used American European Consensus Group (AECG) criteria. With regard to replacing or adding AECG classification criteria, the diagnostic power of salivary gland ultrasonography (SGUS) is promising. Besides being a potential asset for the diagnostic work-up, SGUS might also play a role in monitoring the patient over time. How disease activity in pSS can be assessed has always been an issue, both for patient care and trials. The recently developed EULAR Sjögren's syndrome disease activity index (ESSDAI) and EULAR Sjögren's syndrome patient reported index (ESSPRI) will be discussed including their usefulness for evaluating the effect of biologicals in the treatment of pSS. Recently, the results of a number of biological immunosuppressive drugs have become available. The results of these studies will be discussed in detail taking the effects that can be achieved with traditional treatment into account. The steps to improve early detection, assessments for disease activity and monitoring are important for the development of well designed intervention studies with these promising new drugs. Finally, key advances reported during the last 12 months in understanding the pathogenesis of pSS will be discussed. <h3>Acknowledgements</h3> with thanks to Prof. A. Vissink, Prof. F.K.L. Spijkervet, Prof. F.G.M. Kroese and members of the EULAR working group on Sjögren's syndrome <h3>Disclosure of Interest</h3> H. Bootsma Consultant for: Hoffmann-La Roche, Bristol Myers Squibb, UCB Biosciences Inc.
FRI0201 Are Rheumatic Disease Patient Reported Outcomes Collected Passively and Directly through Smart Phones Feasible? Early Results from A Nation-Wide Pilot Study: Table 1
Authors: K. Michaud, R. Schumacher, K. Wahba, S. Moturu
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) and other rheumatic diseases (RD) are associated with depression, fatigue, and disturbed sleep, symptoms that often impact behavior. Recent advances in reality mining technology combined with the growing use of smartphones have shown measurable changes in phone behavior due to health issues like depression, stress, and influenza. It is unclear if this technology could provide results that could be adopted for improved management of RD patient care. <h3>Objectives</h3> To determine the feasibility of a smartphone app for longitudinal collection of RD patient reported outcomes (PROs). <h3>Methods</h3> In Sep 2013 we invited 700 randomly-selected participants from the Arthritis Internet Registry and the National Data Bank for Rheumatic Diseases, large US observational registries of RD patients who complete semiannual comprehensive questionnaires, who indicated owning a smartphone and being interested in this study. After providing consent, patients were asked to download our app and to complete daily two visual analog scale (VAS) questions on pain and global disease assessment and weekly 12 questions from the Patient Activity Scale-II (PAS-II). After two months, the daily questions ceased while the weekly PAS-II questions continued for 4 more months. We examined the impact of baseline socioeconomics, diagnosis, and clinical status on participation through multivariable logistic regressions. Passive data collected by the app included distance traveled, number of unique calls and text messages, call durations, call counts, and number of missed calls. <h3>Results</h3> Of the 9183 patients surveyed in 2013, only 3204 (35%) reported owning a smartphone. While lower than the national average (∼60%), this was significantly associated with age and income. Of the 700 patients invited, 189 (27%) successfully downloaded the app and submitted PRO data. See Table for socioeconomic and diagnosis breakdown by participation status. Only age was significantly associated with participation. From followup (N=117), 90% thought the daily survey was not burdensome and 62% thought sharing this data with their doctor would improve management of their RD. As of 2014, 7.7K daily and 2.2K weekly surveys were completed with a median (IQR) pain VAS of 3 (1.5, 4.5). Early results show high pain is associated with missed calls, shorter call length, and greater phone mobility. Final results will be available in spring 2014. <h3>Conclusions</h3> We showed that RD patients using a smartphone survey app differed primarily by age. While preliminary results associate smartphone behavior with disease activity, future clinical use may be limited by patient access. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4581
Mucosa of the Small Intestine in Pernicious Anemia
Authors: Parviz Foroozan, Jerry S. Trier
Journal: New England Journal of Medicine (1967)

THE macrocytosis and megaloblastosis consistently seen in the peripheral blood and the bone marrow of patients with severe vitamin B12 deficiency may involve epithelial cells as well. Both cytoplasmic enlargement and nuclear enlargement have been documented in squamous epithelial cells from the oral, esophageal and vaginal mucosa1 , 2 and in columnar epithelial cells from the gastric mucosa1 2 3 in patients with untreated pernicious anemia.However, it has not been established whether the morphology of the mucosa of the small intestine is abnormal in vitamin B12 deficiency not associated with primary disease of the small intestine. Patchy, nonspecific changes in the . . .
TREATMENT OF PARKINSONISM
Authors: ELIERE J. TOLAN, JOHN OLARIU
Journal: American Journal of Psychiatry (1957)

Parkinsonism presents a notoriously discouraging therapeutic problem, since no treatment heretofore employed has significantly altered the course of the disease. Recent work with antihistamines suggests that certain of these compounds may have value in the Parkinsonian syndromes. Promethazine chemically resembles chlorpromazine, which is known to be active upon the extrapyramidal system and related areas. It was decided to investigate the potential value of promethazine since it was believed that the compound might also affect the extrapyramidal structures but in a different way. Twelve patients with advanced Parkinsonism (associated with cerebral arteriosclerosis in 5, of the postencephalitic type in 2, and of the idiopathic type in 5) received promethazine in conservative dosage by mouth for periods totaling 2 to 16 weeks. Among the patients with Parkinsonism, 11 (91%) showed some evidence of improvement, which was not limited to motor activity alone but in most cases involved other physical and behavioral spheres in which there had been severe deterioration. One-third showed clinical change of an unusual degree. Further study of promethazine in Parkinsonian syndromes and the associated mental disorders is suggested, especially for aged and arteriosclerotic patients.
Development of Third-generation Cocal Envelope Producer Cell Lines for Robust Lentiviral Gene Transfer into Hematopoietic Stem Cells and T-cells
Authors: Olivier Humbert, Don W. Gisch, Martin E. Wohlfahrt, Amie B. Adams, Phil D. Greenberg, Tom M. Schmitt, Grant D. Trobridge, Hans-Peter Kiem
Journal: Molecular Therapy (2016)

Lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G) have demonstrated great promise in gene therapy trials employing hematopoietic stem cell and T-cells. The VSV-G envelope confers broad tropism and stability to the vector but is toxic when constitutively expressed, which has impeded efforts to generate stable producer cell lines. We previously showed that cocal pseudotyped LVs offer an excellent alternative to VSV-G vectors because of their broad tropism and resistance to human serum inactivation. In this study, we demonstrate that cocal LVs transduce CD34+ and CD4+ T-cells more efficiently than VSV-G LVs and share the same receptor(s) for cell entry. 293T-cells stably expressing the cocal envelope produced significantly higher LV titers than VSV-G expressing cells. We developed cocal pseudotyped, third-generation, self-inactivating LV producer cell lines for a GFP reporter and for a WT1 tumor-specific T-cell receptor, which achieved concentrated titers above 108 IU/ml and were successfully adapted for growth in suspension, serum-free culture. The resulting LVs were at least as effective as standard LVs in transducing CD34+ and CD4+ T-cells. Our stable cocal LV producer cell lines should facilitate the production of large-scale, high titer clinical grade vectors. Lentiviral vectors (LVs) pseudotyped with vesicular stomatitis virus envelope glycoprotein (VSV-G) have demonstrated great promise in gene therapy trials employing hematopoietic stem cell and T-cells. The VSV-G envelope confers broad tropism and stability to the vector but is toxic when constitutively expressed, which has impeded efforts to generate stable producer cell lines. We previously showed that cocal pseudotyped LVs offer an excellent alternative to VSV-G vectors because of their broad tropism and resistance to human serum inactivation. In this study, we demonstrate that cocal LVs transduce CD34+ and CD4+ T-cells more efficiently than VSV-G LVs and share the same receptor(s) for cell entry. 293T-cells stably expressing the cocal envelope produced significantly higher LV titers than VSV-G expressing cells. We developed cocal pseudotyped, third-generation, self-inactivating LV producer cell lines for a GFP reporter and for a WT1 tumor-specific T-cell receptor, which achieved concentrated titers above 108 IU/ml and were successfully adapted for growth in suspension, serum-free culture. The resulting LVs were at least as effective as standard LVs in transducing CD34+ and CD4+ T-cells. Our stable cocal LV producer cell lines should facilitate the production of large-scale, high titer clinical grade vectors.