tbuckley/cabot-search huggingface dataset:
AB0618 Comparison of Selected Serological and Clinical Parameters in Female and Male Patients with Systemic Sclerosis
Authors: E. Wielosz, M. Majdan, D. Suszek, M. Dryglewska
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The course of systemic sclerosis (SSc) can differ in female and male patients. It has been suggested earlier that in male patients, the incidence rates of diffuse cutaneous SSc, scleroderma renal crisis and digital ulceration are higher. <h3>Objectives</h3> The aim of the study was to compare the selected serological and clinical parameters in male and female patients with SSc. <h3>Methods</h3> The study encompassed 101 patients with SSc, including 23 men, hospitalised in the Department of Rheumatology and Connective Tissue Diseases in the years 2006-2012 (Table 1). The study groups of men and women were assessed according to the SSc subtype, presence of antinuclear antibodies considered SSc markers and incidence of internal organ involvement <h3>Results</h3> There were no statistically significant differences in the incidence of a-Scl-70 and anti-centromere antibodies observed in the groups of female and male patients. The incidence of scleroderma renal crisis was significantly higher in the male group (3/23 vs. 2/78 p=0.04). On the other hand, the incidence of calcifications was significantly lower in the male group compared to the female group (1/23 vs. 20/78 p=0.02). Diffuse cutaneous SSc was observed more commonly in men than in women (13/23 vs. 25/78 p=0.03). The time from development of Raynaud9s phenomenon to the diagnosis was significantly shorter in male patients compared to female patients (3.2±4.7 vs. 7.5±7.1). <h3>Conclusions</h3> The serological profiles of female and male patients with SSc are comparable. The incidence of diffuse cutaneous SSc is higher in men compared to women. The time from development of Raynaud9s phenomenon to the diagnosis is shorter in the male group than in the female group. The incidence of scleroderma renal crisis is higher, whereas of calcifications - is lower in SSc men compared to SSc women. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1286
A1.27 Identification of an antigen-specific regulatory B cell subset in humans
Authors: C Goutsmedt, L Le Pottier, JO Pers
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Several studies in mice have suggested that the B cell receptor (BCR) stimulation in addition to CD40 was required for regulatory B cell (Breg) development. Fault of model in humans, the effect of an antigen-specific stimulation on the regulatory function of B cells has never been studied. We took advantage of the influenza vaccination campaign to study the regulatory function of B cells in response to hemagglutinin (HA), the antigen contained in the vaccine. <h3>Material and methods</h3> B and T cells were isolated from blood of 19 healthy donors before (W0), 3 weeks (W3), 3 months and 6 months after vaccination. To evaluate the functional regulatory properties of peripheral blood B cells in the presence or absence of rHA (antigen-specific stimulation) or a (Fab')2 anti-IgM Ab used to stimulate BCR (polyclonal stimulation), a co-culture assay was performed to assess the ability of pre-activated B cells with multimeric forms of CD40L to inhibit polyclonal anti-CD3 and anti-CD28 Ab-induced proliferation of autologous T cells. Antigen specific B cells (B HA+) have been phenotyped by FACS. <h3>Results</h3> Influenza vaccination induces HA specific B cells (B HA<sup>+</sup>) (2.52 ± 0.1% at W3 vs. 0.95 ± 0.1% at W0, p &lt; 0.001). Before vaccination, when B cells were added to the co-culture assay, the proliferative response of T cells was inhibited by 19.2 ± 2.5%, confirming their regulatory function. The addition of rHA has no additive effect whilst BCR engagement enhanced the suppressive effect of B cells on T cell proliferation (21.1 ± 2.6% vs. 35.3 ± 3.8%, p &lt; 0.005). Interestingly, when the same experiment was performed 3 weeks after influenza vaccination, the presence of rHA in the co-culture assay increased the regulatory function of B cells (32.7 ± 3.5% of T cell proliferation inhibition with rHA versus 22.6 ± 2.6% without rHA, p &lt; 0.001) without achieving the inhibition of T cell proliferation observed after BCR engagement (37.3 ± 4.3%). The regulatory functions of B cells pass through the induction of regulatory T cells and the secretion of TGFβ in an IL-10-independent manner. We identified by FACS analysis after vaccination, a B cell subset specific for HA (CD19<sup>+</sup> HA<sup>+</sup> IgD<sup>+</sup>CD38<sup>+</sup> CD27<sup>-</sup> CD24<sup>-</sup>CD22<sup>+</sup>)that was positively correlated with the increase in the inhibition of T cell proliferation in response to HA. <h3>Conclusions</h3> After vaccination, an antigen-specific B cell subset prone to be induced in Bregs is generated in addition to antigen-specific effector B cells.
A Worldwide Study of the Huntington's Disease Mutation: The Sensitivity and Specificity of Measuring CAG Repeats
Authors: Berry Kremer, Paul Goldberg, Susan E. Andrew, Jane Theilmann, Hakan Telenius, Jutta Zeisler, Ferdinando Squitieri, Biaoyang Lin, Ann Bassett, Elizabeth Almqvist, Thomas D. Bird, Michael R. Hayden
Journal: New England Journal of Medicine (1994)

Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined.
Abstract 2841: A simplified approach to measuring thymidine kinase activity in cells, tumors, and blood as a biomarker of tumor proliferative potential
Authors: Wenlin Li, Xiaolin Kang, Kristian E. Kindt, Cathy Zhang, Mary Spilker, Pamela J. Berlinski, Michael Eisenbraun, Zhengming Yan, Mark Elliott, J. Alan Arbuckle, Morse Faria, H. Thomas Karnes, Peter J. O'Brien
Journal: Cancer Research (2012)

Abstract Understanding tumor size and growth is essential for preclinical oncology drug development, but costs and technical hurdles can prevent accurate, repeated measurements of cell proliferation and tumor growth. Many investigators instead measure the accumulation of nucleosides and analogs (e.g., [18F]-FLT; [3H]-Thy; BrdU) in cells and tissues, a manifestation of thymidine kinase 1 activity (TK1a). These methods can be costly and laborious, and can generate significant hazardous waste, promoting the use of even less-direct measures of cell division. Seeking further insights into the role of TK1 in cancer, we developed rapid, robust, non-isotopic methods that measure TK1a in tissue extracts and blood. In this approach, samples are exposed to FLT in vivo or in vitro, promoting its phosphorylation. Subsequently, nucleosides and their phosphorylated metabolites are isolated for analysis by a simple organic extraction. Using these methods, TK1a was measured in primary and transformed cells, and showed excellent comparability with established proliferation assays including 3H-thymidine incorporation, ATP generation, and fluorescent dye dilution flow cytometry. In drug screens, our method was as sensitive as commercial viability assays, and typically detected drug effects much sooner than those less-specific measures. We also demonstrated chemotherapy-induced alterations in TK1a in xenografted tumor tissue that were comparable to results obtained using radioisotopes. Finally, this approach was adapted to measure TK1a in blood samples. Consistent with published reports, circulating TK1a correlated well with tumor burden in solid tumor models and primary canine hematological cancer. These methods require only small sample volumes (&amp;lt;50μL serum or other biofluids, or a few thousand cells), allowing serial blood collection for monitoring tumor growth kinetics in rodents. These translational studies are underway, and should greatly inform our understanding of the role of TK1 in tumor responses to treatment in vitro and in vivo. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2841. doi:1538-7445.AM2012-2841
Abstract 4111: SDF1/CXCR4 regulates stiffness of bone marrow stromal cell through RhoA and Rac1 GTPases pathway to support myeloma cell proliferation in multiple myeloma.
Authors: Dan Wu, Jing Su, Qianqian Song, Xiaobo Zhou
Journal: Cancer Research (2013)

Abstract Abstract As the second most prevalent hematologic malignancy, multiple myeloma (MM) remains high incurable and relapse owing to intrinsic or acquired drug resistance. Therefore, new therapeutic strategies that are active in drug resistance and target molecular processes of MM progress are attractive. MM is characterized by bone marrow infiltration of malignant plasma cells. The bone marrow microenvironment is a complex structure of various extracellular components and many cell types including haematopoietic stem cells, bone marrow stromal cells (BMSCs), immune cells, bone marrow endothelial cells, as well as osteoclasts and osteoblasts. Recently study showed the physical interaction of multiple myeloma cells with BMSCs from patients of multiple myeloma in the bone marrow milieu, provokes a positive feedback loop and results in multiple myeloma pathogenesis. We observed the myeloma BMSCs are much stiffer and more contractile than normal BMSCs. Stiffer hydrogels support colony formation and adhension of MM better than softer hydrogels. These suggested that myeloma BMSCs provide myeloma cell-friendly microenvironments for myeloma cells via exerting biomechanical forces. In order to elucidate the molecular mechanisms leading to the change of myeloma BMSCs biochemical phenotype, we analyzed myeloma BMSCs and normal BMSCs gene expression profiles. Microarray data analysis demonstrated stromal cell derived factor-1(SDF1) was over expressed in MM BMSCs. In vitro, 100ng/ml SDF1 significantly induced actin polymerization and polarization in MM BMSCs, but not in normal BMSCs. In order to understand how SDF1 regulate BMSCs’ contractile, we conducted reverse phase protein array (RPPA) experiment. Based on RPPA data, we determined RhoA and Rac1 GTPases played important roles in SDF1 induced stiffer of BMSCs. Western blot results also approved SDF1 increased phosphate RhoA and phosphate Rac1 expression level. In conclusion, we characterized the pivotal role of RhoA and Rac1 GTPases in regulating BMSCs stiffness and BMSCs-MM interaction. Targeting biomechanics of BMSCs in myeloma patients, restoring to their normal state would be essential for the long term cure of myeloma, provoking RhoA and Rac1 pathway as novel MM therapy. Citation Format: Dan Wu, Jing Su, Qianqian Song, Xiaobo Zhou. SDF1/CXCR4 regulates stiffness of bone marrow stromal cell through RhoA and Rac1 GTPases pathway to support myeloma cell proliferation in multiple myeloma. [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 4111. doi:10.1158/1538-7445.AM2013-4111
Thrombotic Thrombocytopenic Purpura Associated with Clopidogrel
Authors: Charles L. Bennett, Jean M. Connors, John M. Carwile, Joel L. Moake, William R. Bell, Stefano R. Tarantolo, Leo J. McCarthy, Ravindra Sarode, Amy J. Hatfield, Marc D. Feldman, Charles J. Davidson, Han-Mou Tsai
Journal: New England Journal of Medicine (2000)

The antiplatelet drug clopidogrel is a new thienopyridine derivative whose mechanism of action and chemical structure are similar to those of ticlopidine. The estimated incidence of ticlopidine-associated thrombotic thrombocytopenic purpura is 1 per 1600 to 5000 patients treated, whereas no clopidogrel-associated cases were observed among 20,000 closely monitored patients treated in phase 3 clinical trials and cohort studies. Because of the association between ticlopidine use and thrombotic thrombocytopenic purpura and other adverse effects, clopidogrel has largely replaced ticlopidine in clinical practice. More than 3 million patients have received clopidogrel. We report the clinical and laboratory findings in 11 patients in whom thrombotic thrombocytopenic purpura developed during or soon after treatment with clopidogrel.The 11 patients were identified by active surveillance by the medical directors of blood banks (3 patients), hematologists (6), and the manufacturer of clopidogrel (2).Ten of the 11 patients received clopidogrel for 14 days or less before the onset of thrombotic thrombocytopenic purpura. Although 10 of the 11 patients had a response to plasma exchange, 2 required 20 or more exchanges before clinical improvement occurred, and 2 had relapses while not receiving clopidogrel. One patient died despite undergoing plasma exchange soon after diagnosis.Thrombotic thrombocytopenic purpura can occur after the initiation of clopidogrel therapy, often within the first two weeks of treatment. Physicians should be aware of the possibility of this syndrome when initiating clopidogrel treatment.
Abstract 509: Immunoglobulin reactivity analysis of chronic lymphocytic leukemia patients unveils Lymphocyte Cytosolic Protein 1 (LCP1) as a novel CLL exosome antigen
Authors: Jason A. Dubovsky, Leslie A. Andritsos, William Blum, Amy Johnson, Natarajan Muthusamy, John C. Byrd
Journal: Cancer Research (2012)

Abstract Chronic lymphocytic leukemia (CLL) is incurable accumulation of malignant clonal B lymphocytes in the blood, bone marrow, lymph nodes, and spleen. A hallmark of CLL is profound immunosupression mediated by a litany of costimulatory, cytokine, and exosome signals within the microenvironment. One of the most promising recent advances in this disease has been the development of membrane targeted immunotherapeutics such as the monoclonal antibodies rituximab and alemtuzumab. However, a shortfall of most current and experimental immunotherapeutics is the reliance upon cluster of differentiation (CD) antigens that are also common to a variety of healthy tissues. Moreover, the non-obligate nature of many CD markers renders them susceptible to shedding and down- modulation in resistant CLL cases. In recent studies, we and others have identified endogenous adaptive immune responses against known CLL specific antigens such as ROR1. Curiously, this effect appears biased to tumor relevant antigens with defined malignant signaling. Using retrospective antigen identifications as proof of principle, we sought to further investigate humoral reactivity against autologous CLL membrane associated antigens to identify novel targets for immunotherapy. Mass spectroscopic analysis of CLL membrane antigens targeted by patient derived serum IgG repeatedly identified LCP1 as a lymphocyte specific target. Confirmation by immunoblot and ELISA revealed that CLL patients maintain elevated LCP1 IgG response despite an inability to respond to common vaccine antigens such as tetanus toxin, suggesting continued antigenic stimulation. Flow cytometry, RT-PCR, immunoblot, and confocal microscopic analyses revealed few differences in LCP1 protein levels, glyocoslyation, transcripts, and localization between healthy and malignant B lymphocytes. Given the potential for CLL exosomes to provide a vehicle for continued antigenic stimulation as well as a target for future therapeutics we investigated their LCP1 content. We found that LCP1 is an integral component of CLL exosomes and that production of LCP1-laden exosomes is increased upon CLL stimulation. Ongoing studies aimed at addressing the potential role of exosomal LCP1 in CLL will be discussed. Supported in part by NIH and D. Warren Brown Foundation Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 509. doi:1538-7445.AM2012-509
Esophagitis and Alendronate
Authors: Uri A. Liberman, Laurence J. Hirsch
Journal: New England Journal of Medicine (1996)

To the Editor: Post-marketing reports of severe esophagitis associated with the use of alendronate sodium, reported in this issue of the Journal by de Groen et al.,1 prompted us to reexamine in detail adverse esophageal effects in our three-year osteoporosis studies (Nov. 30, 1995, issue).2 In these studies, 994 patients were randomly assigned to receive placebo, 5 or 10 mg of alendronate daily for three years, or 20 mg of alendronate for two years followed by 5 mg daily in year 3 (ratio of assignments to the four groups, 2:1:1:1, respectively). We used the same terms suggesting esophageal irritation that . . .
Autosomal Dominant Familial Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia
Authors: Rudolf W. Bilous, George Murty, David B. Parkinson, Rajesh V. Thakker, Malcolm G. Coulthard, John Burn, David Mathias, Pat Kendall-Taylor
Journal: New England Journal of Medicine (1992)

FAMILIAL hypoparathyroidism is an unusual condition that can present at any time from early infancy until well into adulthood.1 2 3 4 It can be inherited in an autosomal dominant,3 , 4 autosomal recessive,5 or X-linked recessive6 , 7 pattern. Its presence has been associated with other congenital abnormalities, such as absence of the thymus (DiGeorge's syndrome).8 We recently encountered a patient with long-standing sensorineural deafness who presented with symptoms of thirst and polyuria and was found to have diabetes mellitus. He also had hypocalcemia, subsequently proved to be due to hypoparathyroidism, and a high serum creatinine concentration; further studies revealed small kidneys with a large right-sided . . .
Abstract 1641: Color-coded imaging of interaction between RFP-expressing blood vessels and αv integrin-GFP expressing osteosarcoma cells.
Authors: Fuminori Uehara, Yasunori Tome, Hiroki Maehara, Fuminori Kanaya, Robert M. Hoffman
Journal: Cancer Research (2013)

Abstract We report here imaging the interaction between αv integrin tagged to GFP in human osteosarcoma cells and blood vessels growing on Gelfoam@ implanted subcutaneously in mice. 143B osteosarcoma cells expressing αv integrin-GFP were generated by transfection of an αv integrin-GFP vector. Gelfoam@ (5×5 mm) was treated with basic fibroblast growth factor (bFGF) and transplanted subcutaneously in RFP transgenic nude mice. Skin-flap imaging windows were made at days 7, 14, 21, 28 after transplantation of Gelfoam@. Angiogenesis was observed in the Gelfoam@ using fluorescence imaging via the skin flap windows. Frozen sections were made at day 28 after Gelfoam@ transplantation. RFP-expressing blood vessels were imaged growing into the Gelfoam@. Immunohistochemical (IHC) staining showed that CD31 and RFP fluorescence co-localized in the newly formed RFP-expressing blood vessels in the Gelfoam@. To observe the interaction of tumor cells and RFP blood vessels, 143B cells (5×105),expressing αv integrin-GFP, were injected into the Gelfoam@ 7 days after transplantation. Seven days after cancer-cell injection, the cancer cells were observed in the Gelfoam@ by confocal microscopy via skin-flap windows. 143B cells expressing αv integrin-GFP proliferated into the Gelfoam@ as observed by skin-flap-window imaging. Strong expression of αv integrin-GFP cells was observed near RFP vessels in the Gelfoam@ in the RFP mice 28 days after cancer cell injection. The results show that Gelfoam@ is a useful tool to observe angiogensis in vivo and the interactions of αv integrin-GFP with blood vessels which will allow further understanding of its role in angiogenesis and tumor progression. Citation Format: Fuminori Uehara, Yasunori Tome, Hiroki Maehara, Fuminori Kanaya, Robert M. Hoffman. Color-coded imaging of interaction between RFP-expressing blood vessels and αv integrin-GFP expressing osteosarcoma cells. [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 1641. doi:10.1158/1538-7445.AM2013-1641
1376 LIVER TOXICITY OF THE MOST RECENTLY APPROVED ANTIRETROVIRAL DRUGS IN HIV-INFECTED PATIENTS - OVERALL LOW RATE BUT INCREASED IN THE PRESENCE OF CHRONIC HEPATITIS C
Authors: E. Vispo, J.V. Fernandez-Montero, P. Labarga, P. Barreiro, V. Soriano
Journal: Journal of Hepatology (2012)
P65 * DEREGULATED MICRORNAS IN SERUM AS BIOMARKERS FOR GLIOMA
Authors: C. Tumilson, J. Alder, R. Lea, L. Shaw
Journal: Neuro-Oncology (2014)

INTRODUCTION: Gliomas, including glioblastoma, release both microvesicles containing microRNA (miRNA) and miRNA-protein complexes which can be isolated from biological fluids such as serum. Circulating miRNA can be used as biomarkers for earlier diagnosis, predicting response to treatment and for prognostic information. The aim of this study was to identify a panel of circulating miRNA biomarkers for glioma. METHOD: MiRNAs were isolated from the sera of GBM (n = 26) and control patients (n = 23), using phenol-chloroform extraction. The relative expression of 84 miRNAs was determined using qRT-PCR. 26 miRNAs were selected for further analysis and a final panel of three miRNAs were analysed in a larger patient set. Data were normalised using a synthetic spike-in and analysed using the delta Ct method. Statistical significance was determined using a Mann-Whitney t-test and one way ANOVA with a Bonferroni post-hoc test, a p-value <0.05 was considered significant. RESULTS: Three miRNAs were differentially expressed in the sera of GBM patients compared to controls. MiRNA-X was significantly up-regulated in the sera of a subset of GBM patients,these individuals exhibited an increased survival time compared to those with no up-regulation in miRNA-X shown by Kaplan-Meier survival analysis. MiRNA-Y was found to be significantly down-regulated in the sera of male GBM patients. MiRNA-Z was significantly up-regulated in the sera of GBM patients over the age of 60 compared to age matched controls. CONCLUSION: In summary, we have identified three miRNAs that could be used as a diagnostic panel for GBM. Further investigation will determine their role in glioblastoma and validate their use as biomarkers.