tbuckley/cabot-search huggingface dataset:
Coronary Heart Disease and Genetic Variants with Low Phospholipase A<sub>2</sub> Activity
Authors: Linda M Polfus, Richard A Gibbs, Eric Boerwinkle
Journal: New England Journal of Medicine (2015)

To the Editor: Genetic studies, particularly studies of rare loss-of-function variants, have been good predictors of the success of targeted drugs that lower levels of risk factors and the risk of disease. 1,2Lipoprotein-associated phospholipase A 2 , which is encoded by the PLA2G7 gene, hydrolyzes oxidized phosphatidylcholine to release oxidized nonesterified fatty acids and lysophosphatidylcholine, which up-regulate monocyte adhesion molecules and the chemotactic mediator, MCP-1. 3Elevated lipoprotein-associated phospholipase A 2 activity is positively associated with coronary heart disease. 4 Following the lead of researchers who have conducted studies of proprotein convertase subtilisin/kexin type 9 (PCSK9) loss-of-function mutations, 1 we sequenced the exomes of 6325 participants in the Atherosclerosis Risk in Communities study in search of genetic variants that lower lipoprotein-associated phospholipase A 2 activity.We
The Kinetics of Allergen-induced Eotaxin Level in Nasal Lavage Fluid
Authors: NOBUHISA TERADA, NANAKO HAMANO, WOO JEONG KIM, KOICHI HIRAI, TOSHIHARU NAKAJIMA, HIROKAZU YAMADA, HIROSHI KAWASAKI, TETSUJI YAMASHITA, HIROHISA KISHI, TOMOHIRO NOMURA, TSUTOMU NUMATA, OSAMU YOSHIE, AKIYOSHI KONNO
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Eotaxin (CCL11) is a potent eosinophil chemoattractant belonging to the C-C chemokine. To evaluate the role of eotaxin in eosinophilic inflammation in nasal mucosa, we investigated the levels of eosinophil chemoattractants in nasal lavage fluids obtained after antigen challenge, compared with eosinophil counts and eosinophil protein X (EPX) levels. In subjects with allergic rhinitis, allergen challenge led to parallel increases in eosinophil counts, levels of EPX, and eotaxin concentrations in nasal lavage fluid. The levels of eotaxin in lavage samples showed strong correlation with lavage levels of eosinophil counts and EPX. Normal subjects had few, if any, eosinophils and EPX as well as the measured parameters in their nasal lavage fluids before and after antigen challenge. In our experiments of eosinophil endothelial transmigration (TEM) assay using the nasal microvascular endothelial cells, eotaxin showed the most potent effect among various eosinophil chemoattractants. In addition, treatment of eosinophils with anti-CCR-3 mAb significantly blocked eosinophil TEM induced by homogenate of nasal mucosa. These results indicate that eotaxin has an important role in eosinophil-dependent inflammation in nasal mucosa and suggest that blocking eotaxin or CCR-3 might be useful for new therapeutic tools of allergic rhinitis.
AB0555 Correlations between RF and ACPA dynamics and achievement of response in active rheumatoid arthritis patients treated with rituximab
Authors: M. Florea, A. Rosu, P. Ciurea, F.A. Vreju, A. Musetescu, O. Gofita Cojocaru, C. Hoanca
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory joint disease with a prevalence ranging from 0,5-1% in the general population, associated with premature mortality, disability and compromised quality of life. The classification criteria for RA (American College of Rheumatology/European League Against Rheumatism classification criteria for rheumatoid arthritis – the 2010 ACR/EULAR classification criteria for RA) was introduced in 2010 as a tool with high sensitivity and specificity for diagnosing RA, including anti-cyclic citrullinated peptide antibodies (ACPA) and rheumatoid factor (RF). Rituximab (RTX) has been shown to be an effective RA treatment for use in anti tumor necrosis alpha (TNF-alpha) refractory disease. <h3>Objectives</h3> The aim of the study is to establish the dynamic correlation of ACPA and RF patterns with Disease Activity Score 28 – C reactive protein (DAS28-CRP), after the third completed cure. <h3>Methods</h3> The study included 45 active RA (DAS28 &gt;5,1) subjects with a mean age of 48 years, 88,8% were women with mean disease duration of 7,1 years; all subjects had failed to at least one anti-TNF-alpha regimen and were RTX naive. All the patients were RF-positive, 91,1% were ACPA positive at the inclusion testing and DAS28 was determined each time one day prior the RTX cure. A moderate response was considered as a decrease of DAS28 of at least 1.2 from the prior value. <h3>Results</h3> Moderate response to RTX was observed in 41 cases (91,1%). 33 subjects from responders (80,5%) showed also a significant decrease (more than 50% from initial testing levels) of both RF and ACPA. The number of previous anti-TNF agents (<i>p</i>=0.003), RF positivity (<i>p</i>&lt;0.0001) and ACPA positivity (<i>p</i>=0.003) were associated with EULAR moderate response after the third RTX cure by univariate analysis. Multivariate analysis confirmed that a lower number of anti-TNF agents failed before RTX and both RF and ACPA positivity - were the selected variables associated with a moderate response. Significant decrease of both RF and ACPA was correlated with EULAR moderate response both in the univariate and in the multivariate analysis. <h3>Conclusions</h3> RF and ACPA positive RA patients with a lower number of previously failed TNF blockers may be the best candidates to RTX. Decrease of RF and ACPA levels is significantly correlated with the achievement of a moderate response to RTX. <h3>Disclosure of Interest</h3> None Declared
S85 Neutrophil Cell Membrane Expression of Proteinase 3 and Its Relationship to Alpha-1-Antitrypsin Deficiency (A1ATD)
Authors: NJ Sinden, E Sapey, GM Walton, RA Stockley
Journal: Thorax (2012)

<h3>Introduction</h3> Serine proteinases such as proteinase 3 (PR3) and neutrophil elastase (NE) on the surface of activated neutrophils retain their activity, which may be central to the tissue damage in emphysema. However, little is known about this expression in A1ATD when it may be more critical. <h3>Aims</h3> To compare neutrophil surface expression of PR3 and NE in patients with A1ATD, usual COPD and healthy controls. To determine the influence of the local concentration of A1AT on neutrophil surface expression of PR3 and NE. <h3>Methods</h3> Clinically stable patients with A1ATD (n=9), COPD (n=6) and healthy controls (n=9) were recruited. Neutrophils were isolated from blood. Half were stimulated with fMLP and half were unstimulated. Membrane expression of NE and PR3 was measured by flow cytometry. Neutrophils isolated from six further healthy controls were stimulated in the presence of either normal (PiMM) or A1ATD plasma (PiZZ). Membrane expression of NE and PR3 was measured. <h3>Results</h3> PR3 expression on the surface of unstimulated neutrophils was greater in A1ATD patients (2365±305MFI) compared to healthy controls (1517±253MFI; p=0.048) and COPD patients (1360±315MFI; p=0.046). NE expression was similar between groups. PR3 expression on stimulated neutrophils was greater in A1ATD patients (5112±547MFI) compared to healthy controls (3411±541MFI; p=0.042), but not different to COPD patients (4723±1509MFI; p=0.78). NE expression was similar between groups. When neutrophils from healthy controls were stimulated in the presence of plasma, the surface expression of PR3 (but not NE) was greater (p=0.031) in the presence of PiZZ plasma (1921MFI) compared to PiMM plasma (1352MFI), but less than that observed without plasma. <h3>Conclusions</h3> Baseline neutrophil surface expression of PR3 is greater in A1ATD patients compared to healthy controls. Neutrophils express more PR3 when stimulated in an environment with low concentrations of A1AT, suggesting that membrane binding is dependent on the ability of A1AT to bind released PR3 but not NE. This may have clinical significance for A1ATD emphysema since active membrane-bound PR3 is resistant to inhibitors and can replicate the pathological features associated classically with NE. These findings may explain the association of Wegener’s granulomatosis (where PR3 is an autoantigen) with A1ATD.
P77 Children's exposure to airborne fine particulate matter at home and asthma outcomes
Authors: K. Woods, A. Apsley, S. Semple, S. W. Turner
Journal: Thorax (2010)

<h3>Objectives</h3> The relationship between indoor air exposure to fine particulate (PM<sub>2.5</sub>) and asthma symptoms in children is uncertain. The aim of the present study was to relate PM<sub>2.5</sub> exposure to indices of asthma severity and control. <h3>Methods</h3> Children with asthma were recruited. Disease severity was determined by questionnaire and spirometry. Asthma control was assessed by 5-day peak flow variability and children9s asthma control test (CACT) on the first and fifth day of peak flow testing. Concentrations of PM<sub>2.5</sub> were measured over a 24-h period in the living room and the child9s bedroom. <h3>Results</h3> 22 children were recruited, mean age 11.0 years. Across the 22 homes the median time weighted average (TWA) PM<sub>2.5</sub> concentration (range) in the living room was 7.4 mg/m3 (2.0–150.0) and for the bedroom was 5.6 (3.1, 11.1) mg/m<sup>3</sup> (p=0.04 for comparison with living room). As expected, there was a significantly higher mean TWA PM<sub>2.5</sub> in the living rooms and bedrooms of the seven homes where smoking was reported; 22.0 mg/m<sup>3</sup> for living rooms in smoking homes and 4.7 mg/m<sup>3</sup> for non-smoking homes, p=0.001. There was a positive association between TWA PM<sub>2.5</sub> in the living room and peak flow variability (r=0.51, p=0.027, see Abstract P77 Figure 1) and a negative association between TWA PM<sub>2.5</sub> in the living room and CACT on day 5 (r=−0.48, p=0.037). TWA PM<sub>2.5</sub> exposure was not related to indices of asthma severity including FEV<sub>1</sub> and treatment. Peak PM<sub>2.5</sub> concentration was not associated with any outcome. <h3>Conclusions</h3> This small study suggests that even at relatively low concentrations, there is an exposure-response relationship between increasing indoor air PM<sub>2.5</sub> concentrations, increased airway variability and poorer asthma control in children.
P995 SORAFENIB VERSUS Y-RADIOEMBOLIZATION FOR ADVANCED MONO-LOBAR HEPATOCELLULAR CARCINOMA IN CIRRHOTIC PATIENTS: A PRELIMINARY STUDY ON TOLERABILITY AND SURVIVAL
Authors: S. Gaia, A. Cantamessa, M. Tabone, D. Campion, P. Carucci, M. Grosso, P.R. Brunocilla, A. Risso, A. Calvo, E. Rolle, M. Vesan, F. Brunello, M. Rizzetto
Journal: Journal of Hepatology (2014)
Esophageal duplication cyst causing megaesophagus in a young woman presenting with dysphagia
Authors: Augusto Carbonari, Marcelo Frota, Rogerio Colaiacovo, Lucio Rossini, Romeu Nakamura
Journal: Endoscopy (2014)

A 35-year-old woman had dysphagia to solids for 6 months. Barium esophagram suggested megaesophagus ([Fig. 1]), and endoscopy ([Fig. 2]) showed bulging of the distal esophagus, suggesting extrinsic compression. The patient had no epidemiologic background for Chagas disease. Computed tomography (CT) showed a hypodense lesion in the posterior mediastinum, adjacent to the left atrium and lower esophagus ([Fig. 3]).
Abstract 1811: Cancer/testis antigens: Comprehensive expression analysis and correlation with survival in glioblastoma.
Authors: Marcelo Freitas, Thaís P. Biassi, Suzana M.F Malheiros, João N. Stávale, Fernando T. Zamunér, Maria D.F.S Begnami, Fernando A. Soares, André L. Vettore
Journal: Cancer Research (2013)

Abstract Glioblastoma (GBM) is a highly invasive and aggressive tumor which confers a dismal prognosis despite advances of current therapy. Cancer vaccines have been utilized as treatment of other tumors and might be an option for brain tumors. Cancer/testis (CTA) genes represent promising targets for immunotherapeutic approaches. They are expressed in tumors and expression in normal tissues is exclusively or preferentially restricted to testis. The expression of 31 CTA genes was investigated in 48 glioblastomas and 5 normal brain samples using RT-PCR. A tissue microarray was made and expression of a CTA was detected by immunohistochemical staining. Among the genes with no expression in normal brain CTA1 (57%), CTA2 (54%), CTA3 (44%) and CTA4 (15%) were the most expressed in glioblastomas. At least one of these four selected CTA genes was found expressed in 86% of the GBM cases. Coexpression of two, three and four CTA genes occurred in 25%, 17% and 5% of the examined GBM cases, respectively. CTA4 protein expression was identified in 13% (12/92) of GBM and was negative in all anaplastic astrocytomas (0/15), diffuse astrocytomas (0/48), pilocytic astrocytomas (0/38) and normal brain samples (0/40) evaluated. We found that CTA2-positive GBMs and tumors expressing 3-4 CTA genes presented a significantly better outcome (P = 0.032; hazards ratio = 0.53; 95% CI; 0.28 to 1.0 and P = 0.017, hazards ratio = 0.36; 95% CI, 0.17 to 0.74; respectively). Furthermore, multivariate survival analysis revealed that coexpression of 3-4 CTA genes (P = 0.044, hazards ratio = 0.3, 95%CI = 0.093-0.963), radiotherapy (P = 0.010, hazards ratio = 0.16, 95%CI = 0.04-0.65) and chemotherapy (P = 0.001, hazards ratio = 0.10, 95% CI = 0.03-0.41) remained as independent predictors of overall survival. In conclusion, CTAs are potential targets for immunotherapy in patients with GBM, 86% of the cases examined expressed at least one of four selected CTA genes. The presence of 3-4 CTA genes was associated with better survival, suggesting that these genes might elicit an immune response against GBM. Supported by FAPESP(Grant 2010/20218-2 and 2011/15118-1). Citation Format: Marcelo Freitas, Thaís P. Biassi, Suzana M.F Malheiros, João N. Stávale, Fernando T. Zamunér, Maria D.F.S Begnami, Fernando A. Soares, André L. Vettore. Cancer/testis antigens: Comprehensive expression analysis and correlation with survival in glioblastoma. [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 1811. doi:10.1158/1538-7445.AM2013-1811
Abstract P1-15-06: Incidence of HER2 Positive Quantified by FISH in Ductal Breast Carcinoma In Situ
Authors: I Calvo-Plaza, A Suarez-Gauthier, L Ugidos, F Lopez-Rios, F Perez-Rodriguez, E Garcia-Garcia, E Conde, B Angulo, M Hidalgo, L. Estevez
Journal: Cancer Research (2010)

Abstract Purpose: The Her2/neu gene is amplified and/or its protein is overexpressed in 15-25% of invasive breast cancer, but in Ductal Carcinoma In Situ (DCIS) this expression is highly increased (60-80%). We review our rate of DCIS with Her2 amplified in a prospective series of women with new diagnosis of DCIS. Methods: Patients with new diagnosis of DCIS by biopsy were studied. The status of Her2 was evaluated by fluorescence in situ hybridization (Vysis path vision HER-2 DNA probe kit) and was considered amplified if the ratio HER2/CEP17 was &amp;gt;2.0. The status of estrogen and progesterone receptors were analyzed by inmunohistochemistry (IHQ). Data evaluating architectural pattern and histological grade were also collected. Results: Data from 53 patients with DCIS were included (two patients with combined invasive ductal carcinoma detected at time of surgery and 51 cases of pure DCIS). HER2 was amplified in 20 patients (37%), with HER2/CEP17 ratios between 2.16 to 14.00. A total of 29 patients had grade III DCIS, and of those 18 (62%) had Her2 amplified. 17 patients (32%) were estrogen and progesterone receptors negative (10 with Her2 amplified). We have not observed any correlation about architectural pattern (comedo, cribriform, micropapillary, solid/necrotic) and amplification of Her2. Conclusion: In our series of DCIS patients the Her2 amplification was less commonly found compared to prior studies (37% vs &amp;gt;60%). Most of DCIS were grade 3 (90%) and no relation was found among the architectural pattern and amplification of Her2. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-15-06.
Pre-B-Cell Leukemia
Authors: Larry B. Vogler, William M. Crist, Dale E. Bockman, Elliott R. Pearl, Alexander R. Lawton, Max D. Cooper
Journal: New England Journal of Medicine (1978)

Large lymphoid cells containing small amounts of cytoplasmic IgM (clgM) but undetectable surface immunoglobulin (slg) have recently been recognized as precursors of B lymphocytes. They are a small, rapidly dividing pool of normal marrow lymphoblasts. Since lymphoblasts in most childhood acute lymphoblastic leukemias lack slg and other conventional B-lymphocyte and T-lymphocyte markers, we examined the possibility that some leukemias represent "pre-B"-cell neoplasms. In four of 22 consecutive patients, leukemic cells had the clgM+.slg- phenotype of pre-B cells. These patients' cells shared "common acute-lymphoblastic-leukemia" antigens and "B-cell" alloantigens, but differed in expression of several developmental features characteristic of the B-cell line. Pre-B-cell leukemias were readily responsive to chemotherapy. We conclude that a distinct subpopulation of previously unclassified leukemias reflects oncogenic transformation at the earliest recognizable stage in differentiation along the B-cell axis.
The Effect of Chemotherapy on the Duration of the Carrier State Following Scarlet Fever
Authors: A. Daniel Rubenstein, George E. Foley
Journal: New England Journal of Medicine (1945)

THE utilization of chemoprophylaxis in the control of infections spread by the respiratory tract is a recent development that is gaining ever wider application. In 1939 it was shown that sulfanilamide was effective in preventing streptococcal upper respiratory infections and relapses in rheumatic fever.1 2 3 Kuhns et al.4 found that sulfadiazine, when given prophylactically, diminished meningococcal carrier rates as well as the incidence of meningococcal meningitis. During the course of a scarlet-fever epidemic in a United States naval station, the routine administration of prophylactic doses of sulfadiazine to healthy contacts appeared to be effective in checking its spread.5 Conflicting reports have . . .
AB0258 Patient with rheumatoid arthritis and strategy of treating rheumatoid arthritis to target
Authors: N. Shamsutdinova, S. Yakupova, A. Galimova
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The strategy of treating rheumatoid arthritis (RA) to target involves the interaction between doctor and patient. The successful achievement of the goal is possible only if the patient informed about the treatment target and the strategy planned to reach this target under the supervision of the rheumatologist <h3>Objectives</h3> To evaluate the patient's attitude to the possibility of treating RA to target, to identify possible difficulties in understanding the strategy T2T. <h3>Methods</h3> The study interviewed 30 patients with a diagnosis of RA who visited rheumatologist in Republican Clinical Hospital (Kazan, Russian Federation). We used our developed a questionnaire, which includes 51 questions. <h3>Results</h3> Were investigated 30 patients: 27 women (91%) and 3 men (9%). The average age was 46,6 ± 3,6 years. DMARDs received 90% of patients: 6.7% (2 people) - are taking sulfasalazine, 76.7% (23 people) - methotrexate, 3.3% (1 person) - leflunomide, 3.3% (1 person) - azathioprine. Of these, 46% of patients receiving DMARDs expect prevention of structural damage, normalisation of function, 19% expect a full recovery, 20% expect a more effective pain relief, and 19% just follow doctor's orders. 10% of patients believe that perhaps the cure of RA, 80% - no, while 10% did not know. Moreover, all patients know that they can expect in the absence of treatment (immobility, disability). All patients said that the doctor explained the tactics of treatment of their disease, but 15% of it was incomprehensible. Perhaps this can be explained by the small amount of time the doctor gave an interview with the patient - in an average of 5 to 10 minutes. All of the patients indicated that they could ask questions of your doctor and get all the answers, however, 30% identified that this information is not clear. 100% of patients reported that the explanations in the illustrations would be comfortable. Some of the patients (42.4%) scares need to monitor the disease, mainly due to the strict requirements of lifelong medication (36.3%) and damage to other organs - the liver (18%). None of the patients interviewed had never attended school for RA patients, and 80% said the need for such activities and expressed their desire to participate in educational programs for patients with RA. 77% of patients with RA were talking with the other patients, 85% of them point to a positive experience. <h3>Conclusions</h3> Despite the fact that the majority of patients (90%) were taking DMARDs, some of them are not sufficiently informed about the aims and objectives of the treatment of RA, does not understand the explanation the doctor. To improve the quality of «doctor-patient» interaction is expedient further information programs for patients with illustrative material <h3>Disclosure of Interest</h3> None Declared
Glucocorticoid-Regulated Expression of Exogenous Human Growth Hormone Gene in Rats
Authors: Takeshi Inazawa, Tsuyoshi Tanabe, Harumi Yamada, Takashi Nakaoka, Yoshihide Hashimoto, Tomoko Yamasaki, Hajime Kotaki, Kenzaburo Tani, Shigetaka Asano, Naohide Yamashita
Journal: Molecular Therapy (2001)

The aim of this study was to control in vitro and in vivo expression of the growth hormone (GH) gene using a glucocorticoid-sensitive promoter, the mouse mammary tumor virus long terminal repeat (MMTV LTR). We inserted the cDNA encoding the 20-kDa form of human GH (20K-GH) downstream of the MMTV LTR of plasmid pMSG, and used lipofection to transfer it to 3Y1 cells together with plasmid pMX, which contains a puromycin-resistant element. The secretion of GH from the selected transformants was dose-dependently augmented by the application of hydrocortisone, corticosterone, or dexamethasone, among which dexamethasone was the most potent. Analysis of the time course showed that 20K-GH secretion began to increase within 2 hours after the addition of glucocorticoid and reached a maximal level of about threefold over the unstimulated control at 3 hours; secretion then gradually declined and returned to near basal levels at 19 hours. Repeated glucocorticoid application led to repeated increases in GH secretion. When GH-producing cells were microcapsulated and transplanted into the abdominal cavities of rats, 20K-GH was detected in the plasma under control conditions and increased about 3.3-fold after administration of dexamethasone. We suggest that GH expression driven by the MMTV LTR promoter may be under the control of an endogenous glucocorticoid in vivo.