tbuckley/cabot-search huggingface dataset:
THU0440 Yersinia Enterocolitica Biotype 1A Infection can Trigger Reactive Arthritis
Authors: R. Tuompo, T. Hannu, A. Siitonen, M. Leirisalo-Repo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Yersinia enterocolitica (YE) is a well-known trigger of reactive arthritis (ReA) [1]. Studies of YE-related ReA have concentrated on the traditionally pathogenic serotypes O:3 and O:9 (biotypes 4 and 2, respectively) [2, 3]. Biotype 1A is generally considered non-pathogenic [4]. However, biotype 1A has been isolated from stools of diarrheic patients, and the potential pathogenicity of biotype 1A has been discussed in the literature [5, 6]. <h3>Objectives</h3> To study the capability of YE biotype 1A to induce ReA and other reactive musculoskeletal (MS) symptoms. <h3>Methods</h3> 406 questionnaires were sent to cases with positive stool culture of YE. Analysis of self-reported MS symptoms was supplemented with a clinical examination of subjects with recent MS symptoms. <h3>Results</h3> Of the 295 subjects, who returned the questionnaire, 120 reported MS symptoms, of which 114 were included to the final analysis. Among these 114 patients, 77 (68%) had YE biotype 1A, 16 (14%) had YE biotype 4, and one (0.9%) had biotype 2 infection; the remaining 20 (17%) patients had different YE-like strains or had a non-biotypable strain in the stool specimens. Of the subjects, 18% (21/114) fulfilled the criteria for ReA, and a further 12% (14/114) had other reactive MS symptoms (tendinitis or enthesitis). The incidence of ReA was 6% in cases with YE biotype 1 A and 5.4% in cases with biotypes 4 or 2. <h3>Conclusions</h3> YE biotype 1A can be a causative agent for ReA. Therefore, it should be included among pathogens searched at the diagnostic work up of the aetiology of ReA. <h3>References</h3> Leirisalo-Repo M. Reactive arthritis. Scand J Rheumatol 2005;34:251-9. Leirisalo M, Skylv G, Kousa M, et al. Followup study on patients with Reiter's disease and reactive arthritis, with special reference to HLA-B27. Arthritis Rheum 1982;25:249-9. Schiellerup P, Krogfelt KA, Locht H. A comparison of self-reported joint symptoms following infection with different enteric pathogens: effect of HLA-B27.J Rheumatol. 2008;35:480-7. Bottone EJ. Yersinia enterocolitica: the charisma continues. Clin Microbiol Rev 1997;10:257-76. Tennant SM, Grant TH, Robins-Browne RM. Pathogenicity of Yersinia enterocolitica biotype 1A. FEMS Immunol Med Microbiol 2003;38:127-37. Bhagat N, Virdi JS. The enigma of Yersinia enterocolitica biovar 1A. Crit Rev Microbiol 2010;37:1-15. <h3>Disclosure of Interest</h3> None Declared
P734Leukocyte Bim deficiency induces T cell and immunoglobulin accumulation in atherosclerotic lesions without affecting plaque size
Authors: L Temmerman, M Westra, I Bot, M Bot, K Habets, S De Jager, T Keulers, T Cotter, T Van Berkel, E Biessen
Journal: Cardiovascular Research (2014)

Introduction: Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. Atherosclerosis is a chronic inflammatory process with features of autoimmune disease. We therefore investigated impact of hematopoietic Bim deficiency on plaque formation. Hypothesis: Bim deficient leukocytes will be highly (auto)reactive in a hyperlipidemic setting, increasing plaque apoptosis and necrosis and thus contributing to plaque destabilization. Methods: Bim-/- or wild type bone marrow transplanted LDLr-/- mice were fed a Western type diet for 5 weeks (n=7) or 10 weeks (n=12), after which they were sacrificed, immunophenotyped and atherosclerotic lesions were analyzed. Results: Bim-/- transplanted mice displayed splenomegaly (+81%) and a doubling of circulating lymphocyte counts. Both CD4+ and CD8+ T cells were more activated (increased CD69 and CD71 expression). In Bim deficient mice, a 59% increase in Tbet+ Th1 cells was observed in blood (P<0.001), concomitant with a 43% rise in interferon gamma producing CD4+ Tcells (P<0.001). B cells were elevated by 147%, with a relative shift towards the pro-atherogenic IgG-producing B2 cell phenotype, also reflected by a more than two-fold increase in IgG1 anti-oxLDL antibodies in the serum. Strikingly, plaque size as well as lesion composition or stability (necrotic core, collagen and macrophage content) was unaffected in Bim-/- transplanted mice. Despite massive deposits of IgG complexes in plaques of Bim-/- transplanted mice and a higher presence of lesional T cells (+51%, P<0.05), apoptotic cell content of atherosclerotic lesions remained unchanged. The surprising lack in plaque phenotype despite the profound pro-atherogenic effects on T and B cells may be attributable to a 30-48% (p<0.05) reduction of serum cholesterol levels in Bim-/- transplanted mice. Conclusion: Bim deficient leukocytes are more activated in Western type diet fed LDLr-/- mice and induce high levels of anti-oxLDL autoantibodies. Nevertheless, those significant pro-atherogenic effects are most likely masked by an unexpected reduction in serum cholesterol.
Decreased Phosphorylation of RSK May Predict Response for Neoadjuvant Chemotherapy.
Authors: J. Yi, J. Yu, J. Yu, E. Ko, E. Ko, W. Han, W. Han, D. Noh, D. Noh
Journal: Cancer Research (2009)

Abstract Neo-adjuvant chemotherapy is an essential part of the management of locally advanced breast cancer. The resistance in breast cancer towards chemotherapeutic agents makes chemotherapy an incommodious problem. Current clinical factors cannot predict therapy response sufficiently in the treated patients. Doxorubicin is an effective breast cancer drug but is hampered by a severe, dose-dependent toxicity. The resistance mechanisms responsible for doxorubicin-resistance of breast cancer have been the subject of numerous investigations. Identification of proteins that are associated with doxorubicin resistance is a first step toward better response prediction and tailored treatment of patients.In this study, we compared the expression of core proteins and their phosphorylated forms of several canonical pathways (MAPK signaling, Apoptosis, PI3K/Akt Signaling, Cell Cycle/Checkpoint and TGF-β/Smad signaling) in breast cancer tissues which were divided into two classes based on the type of response to doxorubicin therapy by immunoblotting. As a result, we found that the phosphorylated form of ribosomal protein S6 kinase (RSK) was low in doxorubicin-resistant breast cancer tissues compared with doxorubicin-sensitive breast cancer tissues.We also investigated RSK's phosphorylation rate and doxorubicin sensitivity of various breast cancer cell lines including MCF-7, MCF-7s (sphere form), MDA-MB-231, MDA-MB-231s, MDA-MB-436, MDA-MB-453, MDA-MB-468, ZR75-1, BT474, Hs578T, T47D and MCF-10A to determine the phosphorylation rate of RSK in relation to the drug sensitivity of the breast cancer cell lines. Expectedly, the phosphorylation of RSK was low in doxorubicin resistant breast cancer cell line such as MDA-MB-453, ZR75-1 and Hs578T. Additionally, MCF-7s and MDA-MB-231s showed decreased phosphorylation rates compared with MCF-7 and MDA-MB-231.In conclusion, decreased phosphorylation of RSK may predict response and further clinical studies should evaluate for molecular function of phosphorylated RSK during doxorubicin therapy. Furthermore, immunohistochemistry for the detection of RSK's phosphorylation rate in breast cancer tissues is being developed for the analysis of increased and independent group of patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2146.
CONTRIBUTION TO THE SURVEY OF HANDWRITING
Authors: MAX A. BRUCK
Journal: American Journal of Psychiatry (1956)

1. By applying technical methods and mathematical principles to the survey of Gestalt in handwriting the shift from solely intuitional comprehension to scientific testing and practical evaluation is begun. 2. The tests are performed with the help of a map measure, a simple device which makes a quick integrative measuring possible. 3. On scripts of 27 apparently normal individuals the following hypothesis is tested and found to be justified: The total of the length of words, measured in the middle zone of letters, is related to the total length of lines according to the principle of the "golden section." 4. Among 25 institutionalized mental patients were 9 cases whose scripts revealed proportions not conforming with the principle of the "golden section." 5. The results of this investigation, evaluated by tests of significance, advocate this method as a sort of graphometrical screening test. The author intends to supplement it with other tests, according to the principles of integrative survey.
A Simple Method for Determining the Optimal Dosage of Progestin in Postmenopausal Women Receiving Estrogens
Authors: Malcolm L. Padwick, John Pryse-Davies, Malcolm I. Whitehead
Journal: New England Journal of Medicine (1986)

Progestin is often added to regimens of estrogen therapy in postmenopausal women to reduce the risk of endometrial hyperstimulation, but it may cause undesirable metabolic effects. Therefore, a low dosage is recommended. At present, the only way to determine whether the dosage of progestin is causing the desired secretory transformation of the endometrium is by endometrial sampling, which is invasive. We studied 102 postmenopausal women undergoing estrogen therapy who also took a progestin for 12 days each month, and we correlated the day of onset of bleeding with the endometrial histology over a three-month period. A bleeding pattern suitable for interpretation was observed in 96 women. Regardless of the preparation and dosage of the estrogen and progestin used, wholly or predominantly proliferative endometrium was always associated with bleeding on or before day 10 after the addition of progestin; wholly or predominantly secretory endometrium, or a lack of endometrial tissue, was associated with bleeding on day 11 or later. We conclude that the bleeding pattern reflected the histologic condition of the endometrium and that adjustment of the dosage of progestin so that regular bleeding is induced on or after day 11 may obviate the need for endometrial biopsy.
Culturally and Linguistically Appropriate Services — Advancing Health with CLAS
Authors: Howard K. Koh, J. Nadine Gracia, Mayra E. Alvarez
Journal: New England Journal of Medicine (2014)

To help organizations better serve the increasingly diverse U.S. population, the HHS Office of Minority Health has released enhanced National Standards for Culturally and Linguistically Appropriate Services (CLAS) in Health and Health Care.
P376Ophiobolins redistribute Kv4.x ion channels and connexin26 in cardiac muscle
Authors: V Szuts, M Horvath, M Bolstad, F Otvos, ZS Szegletes, E Welker, JG Kiss, L Rovo, CS Vagvolgyi, K Halasy
Journal: Cardiovascular Research (2014)

Background: Ophiobolins are sesterpene-type secondary metabolites, mostly synthesized by some plant pathogenic fungi (e.g. Bipolaris). Most of the microbial secondary metabolites have substantial effects on humans and animals but the background of their action is poorly known. The synapse-associated protein 97 (SAP97) anchors Kir and Kv ion channels regulating the subcellular translocation and localization of channels. The gap junction protein connexin26 facilitates direct intercellular communication but its role in the heart is indefinite. Aim: In this study we compared the expression and distribution of Kv4.x ion channels, their modulators and connexin26 in cardiomyopathic heart in the presence of ophiobolin as an external stress factor for myocytes. We used rat heart tissues and rat cardiomyocytes using molecular biology methods. Results: We revealed that the Kv4.3 pattern differs from that of Kv4.2 because only Kv4.3 marked the Z-line which is the localization place of the T-tubular system. Ophiobolin P1 (OP1) treatments down-regulated and redistributed the Kv4.2 and Kv4.3 ion channels in the plasma membrane as well as in the mitochondrial and nuclear membrane. Another effect was that the synapse-associated protein 97 did not colocalize with the Kv4.x ion channel α-subunits at the sarcolemma compared to the controls. Atomic force microscope study showed that the Young modulus and the mechanical parameters are altered on the cell surface after 1 day in the presence of OP1. The SAP97 and Kv4 channel subunits colocalize at the sarcolemma of healthy cardiomyocytes but the distribution of these complexes has changed under ophiobolin treatment. Discussion: These results suggest that the anchoring SAP97 and its modulator functions are crucial to maintain the normal ITO current in the heart tissues. In the tripartite complex of Kv4.3-SAP97-CAMKII structure are need to form the physiologically active Kv4 type channels and essential to regulate the subcellular localization of channels in the cardiomyocytes. This work was supported by grants TAMOP-4.2.2.A-11/1/KONV-2012-0035 and TAMOP-4.2.2.A-11/1/KNOV-2012-0052.
P01.07 * IMPACT OF EXTRACELLULAR VESICLES RELEASED BY GLIOBLASTOMA CELLS AFTER IRRADIATION ON TUMOR MICROENVIRONMENT
Authors: H. Ding, S. Pinel, V. Jouan-Hureaux, A. Chateau, C. Boura, B. Faivre
Journal: Neuro-Oncology (2014)

AIMS: Glioblastoma (GBM) is the most lethal of all human tumors. Ionizing radiation (IR), as a major therapeutic modality, induces multiple types of DNA lesions in cells, therefore causes cell death. However, IR could also affect neighboring unirradiated cells, inducing Bystander Effects as chromosomal aberrations, increased proliferation, etc. Intercellular communication through the release of different components is involved in the mechanism. GBM cells release different soluble factors as well as tumor microvesicles (TMVs) to modify the phenotype of neighboring cells, thus participating in the tumor progression. The present study was designed to investigate in vitro the impact of IR on the communication between tumor cells and endothelial cells in the tumor microenvironment via soluble factors and TMVs. MATERIALS AND METHODS: Two GBM cell lines (T98G, U87) were grown and sham-irradiated (0Gy) or irradiated (2 or 10Gy) using a Clinac iX linear accelerator. Cell culture media (CM) were collected. Filtrate (containing only soluble factors) and TMVs were separated with successive centrifugations and Pierce concentrator. Cell viability was assessed by cell counting using trypan blue. TMVs quantifications were performed by flow cytometry. The effect of CM/Filtrate/TMVs on the global behavior (proliferation, adhesion) of bystander tumor cells or HUVEC was investigated using the xCELLigence system (ACEA). RESULTS: As expected, irradiation caused a loss of cell number in U87 and T98G: 20% at 2Gy and 60% at 10Gy 48h post-IR as compared to untreated cells. Both CM and Filtrate collected from sham-irradiated tumor cells induced a 50% reduction of bystander tumor cells proliferation, while CM and Filtrate recovered from 10Gy-irradiated cells had different influence on the proliferation: herein, the inhibitory properties of CM were less marked than those of Filtrate. The discordant effects between CM and Filtrate led us to investigate the role of TMVs. When quantified using flow cytometry, two-fold more TMVs were found in 10Gy-irradiated T98G as compared to untreated cells 48h post-IR, while in U87 this stimulation of release was observed at 2h. TMVs were shown to induce a 2-fold increase of HUVEC cell index. Interestingly after 10Gy-irradiation, TMVs from both cell lines slightly also favored both bystander tumor cells and HUVEC proliferation. CONCLUSION: IR inhibits GBM cells proliferation. IR stimulates TMVs release by GBM cells in a time- and line-dependent manner. IR facilitates tumor progression by stimulating the proliferation of bystander tumor cells as well as favoring tumor angiogenesis via TMVs.
1383 p.Leu75Pro Apo A-I AMYLOIDOSIS CAUSES MACROSCOPICALLY EVIDENT HEPATIC AMYLOIDOSIS IN A PATIENT WITHOUT ANY CLINICAL OR LABORATORY SIGNS OF HEPATIC DYSFUNCTION
Authors: Y. Avsar, T. Spieker, I. Kabar, C. Roecken, H. Wolters, H.H.-J. Schmidt
Journal: Journal of Hepatology (2013)
On asymmetries exhibiting a near-equiprobable distribution of directions
Authors: Robert L. Collins
Journal: Behavioral and Brain Sciences (1981)

In his target article as well as in other writings, Denenberg presents a view of lateralization with which I fundamentally disagree: namely, that an affirmation of lateralization in a population is to be based primarily, if not exclusively, on observing a nonequiprobable distribution of asymmetric forms in that population.
Behaviour and metastatic potential of her2/neu positive and her2/neu negative circulating epithelial tumor cells (CETC) during adjuvant systemic therapy in breast cancer.
Authors: O Camara, U Hammer, M Gajda, T Kroll, S Krauspe, A Gellner, C Joerke, IB Runnebaum, K Hoeffken, K Pachmann
Journal: Cancer Research (2009)

Abstract Abstract #5030 Background: Most tumor patients do not die from the primary tumor but from metastases in vital organs. Here we report on the influence of adjuvant chemotherapy and trastuzumab on the remnant CETC patients with her2/ positive tumors after surgery and the impact on metastasis formation.&amp;#x2028; Material and Methods: Tumor cells were quantified with an automated microscope (Laser Scanning Cytometer®, Icis or ScanR) from anticoagulated blood drawn before each new therapy cycle from patients treated with systemic chemotherapy after surgery and subsequent maintenance therapy with trastuzumab. After red blood cell lysis leucocytes were stained with PE-anti-CD45 and tumor cells with FITC-anti-EpCAM. FISH analysis was performed for determination of the proportion of her2/neu positive cells and changes registered as % increase or decrease. The response to therapy was correlated to outcome.&amp;#x2028; Results: Almost all her2/neu positive breast cancer patients scheduled for systemic treatment had CETC before therapy. A decrease in cell numbers highly correlated with relapse free survival. Her2/neu positive patients responding to therapy with an increase in CETC were at increased risk to develop further increasing cell numbers also during subsequent trastuzumab treatment. Her2/neu positive patients who did never receive trastuzumab all had increasing CETC numbers during the postoperative observation time and all have suffered relapse. Patients who received trastuzumab only after adjuvant treatment all had decreasing CETC numbers and all are in sustained complete remission after up to 4 years. Of the patients who received trastuzumab together with adjuvant treatment those who showed no change or an increase in CETC in spite of trastuzumab had increasing proportions of FISH high amplified cells and a higher risk of relapse than patients with decreasing CETC during trastuzumab.&amp;#x2028; Discussion: Monitoring CETC will not only provide the earliest and most reliable indicator of successful adjuvant treatment and spare patients unnecessary treatment but also patients with the highly aggressive her2/neu positive tumors can be discerned into such with high and low risk of relapse even during trastuzumab therapy. This warrants further therapy studies to control what patients may benefit from addition of e.g. small molecules already during therapy before development of metastases. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5030.
Abstract 4975: Next generation sequencing reveals a connection between KRAS mutation and the NFkB pathway in lung adenocarcinoma samples
Authors: Krishna R. Kalari, David Rossell, Yan Asmann, Asha Nair, Tiffany Baker, Jennifer Carr, High-Seng Chai, Asif Hossain, Zhifu Sun, Ying Li, Sumit Middha, Brian Bot, Jeanette Eckel Passow, Jean-Pierre Kocher, Edith Perez, Alan Fields, Aubrey Thompson
Journal: Cancer Research (2011)

Abstract Motivation: KRAS is commonly mutated in a variety of cancers including lung cancer. The KRAS gene is frequently mutated at codons 12 and 13 in lung adenocarcinomas in patients with a history of smoking. Tumors harboring an activating KRAS mutation are aggressive and are often resistant to available therapies. In the present study, we set out to identify pathways that are specifically altered in lung cancer patients whose tumors harbor a KRAS mutation using next generation sequencing technology. Methods: We performed 50nt paired-end RNA-sequencing in 15 lung adenocarcinoma samples (8 and 7 samples with and without KRAS mutation). Reads were aligned to genome and exon junctions using Illumina's alignment tool ELAND_RNA. CASAVA and Genome Studio data analysis software were used to obtain read counts for genes, exons and exon junctions. We applied a variety of computational methods (Casper R package, Bowtie, TopHat) and softwares (Partek, R statistical software, JMP, Ingenuity Pathway Anlaysis, DAVID) to carry out our analyses. Results: Differential gene expression and splicing analysis were performed between the two groups. We identified 115 genes that were differentially expressed and 112 genes that consist of splicing variants with at least 2 fold changes and p-value &amp;lt; 0.01. We randomly selected 6/15 samples and performed real-time qRT-PCR for 6 differentially expressed genes. Significant correlations were observed ranging from 0.44 to 0.83, when qRT-PCR results were compared with RNA-sequencing expression data. Pathway analysis with 115 differentially expressed genes and 112 splicing variants revealed that the most significant pathway is composed entirely of NFκB focus genes, suggesting that there is a direct connection between oncogenic KRAS and activation of the NFκB signaling pathway. Conclusions: NFκB has been implicated in KRas-mediated formation of early stage lung adenomas in the LSL-Kas mouse model. Our data indicate that this connection also occurs in human lung cancer and establish NFκB activation as a key manifestation of KRAS mutation in human lung cancer. Hence drugs targeting NFκB and NFκB related genes may potentially be helpful for the treatment of patients with oncogenic KRAS mutations. (Supported in part by grants from the 26.2 with Donna Foundation and the Florida Department of Health Bankhead/Coley program.) 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 4975. doi:10.1158/1538-7445.AM2011-4975