tbuckley/cabot-search huggingface dataset:
Development and validation of a questionnaire to measure asthma control
Authors: E.F. Juniper, P.M. O′byrne, G.h Guyatt, P.j Ferrie, D.r King
Journal: European Respiratory Journal (1999)

International guidelines on asthma management indicate that the primary goal of treatment should be optimum asthma control. The aim of this study was to develop and validate the Asthma Control Questionnaire (ACQ). The authors generated a list of all symptoms used to assess control and sent it to 100 asthma clinicians who were members of guidelines committees (18 countries). They scored each symptom for its importance in evaluating asthma control. From the 91 responses, the five highest scoring symptoms were selected for the ACQ. In addition, there is one question on beta2-agonist use and another on airway calibre (total questions=7). The ACQ was tested in a 9-week observational study of 50 adults with symptomatic asthma. The ACQ and other measures of asthma health status were assessed at baseline, 1, 5 and 9 weeks. In patients whose asthma was stable between clinic visits, reliability of the ACQ was high (intraclass correlation coefficient (ICC)=0.90). The questionnaire was very responsive to change in asthma control (p&lt;0.0001). Cross-sectional and longitudinal validity were supported by correlations between the ACQ and other measures of asthma health status being close to a priori predictions. In conclusion, the Asthma Control Questionnaire has strong evaluative and discriminative properties and can be used with confidence to measure asthma control.
B cell depletion reduces the development of atherosclerosis in mice
Authors: Hafid Ait-Oufella, Olivier Herbin, Jean-David Bouaziz, Christoph J. Binder, Catherine Uyttenhove, Ludivine Laurans, Soraya Taleb, Emily Van Vré, Bruno Esposito, José Vilar, Jérôme Sirvent, Jacques Van Snick, Alain Tedgui, Thomas F. Tedder, Ziad Mallat
Journal: The Journal of Experimental Medicine (2010)

B cell depletion significantly reduces the burden of several immune-mediated diseases. However, B cell activation has been until now associated with a protection against atherosclerosis, suggesting that B cell–depleting therapies would enhance cardiovascular risk. We unexpectedly show that mature B cell depletion using a CD20-specific monoclonal antibody induces a significant reduction of atherosclerosis in various mouse models of the disease. This treatment preserves the production of natural and potentially protective anti–oxidized low-density lipoprotein (oxLDL) IgM autoantibodies over IgG type anti-oxLDL antibodies, and markedly reduces pathogenic T cell activation. B cell depletion diminished T cell–derived IFN-γ secretion and enhanced production of IL-17; neutralization of the latter abrogated CD20 antibody–mediated atheroprotection. These results challenge the current paradigm that B cell activation plays an overall protective role in atherogenesis and identify new antiatherogenic strategies based on B cell modulation.
Correlation between radiographically diagnosed osteophytes and magnetic resonance detected cartilage defects in the patellofemoral joint
Authors: T Boegard, O Rudling, I F Petersson, K Jonsson
Journal: Annals of the Rheumatic Diseases (1998)

<h3>OBJECTIVE</h3> To assess the correlation between radiographically diagnosed osteophytes in the axial and lateral view of the patellofemoral joint (PFJ) and (1) magnetic resonance (MR) detected cartilage defects in the same joint and (2) knee pain. <h3>METHODS</h3> Fifty seven pepole with chronic knee pain, (aged 41–58 years, mean 50 years) were examined with axial and lateral radiograms when standing of the right and the left PFJ. The presence and grade of osteophytes was assessed. On the same day, a MR examination was performed of the signal knee with proton density and T2 weighted turbo spin-echo sequences in the sagittal and axial view on a 1.0 T imager. Cartilage defects in the PFJ were noted. The subjects were questioned for current knee pain for each knee. <h3>RESULTS</h3> Osteophytes at the PFJ had a specificity varying between 59 and 100% and a positive predictive value between 74 and 100% for MR detected cartilage defects. The corresponding values for osteophytes at the lateral aspect of the femoral trochlea were both 100%. In PFJ with narrowing (&lt;5 mm) osteophytes had a sensitivity and a positive predictive value of 90 and 95% respectively for MR detected cartilage defects, while in PFJ with non-narrowing (⩾5 mm) the corresponding values were 75 and 65% and the specificity was 50%. A correlation (p&lt;0.05) between osteophytes at the inferior pole of the patella and knee pain was found. <h3>CONCLUSIONS</h3> Osteophytes at the PFJ are associated with MR detected cartilage defects in the same joint. The relation was strong for osteophytes at the lateral femoral trochlea and in the PFJ with narrowing (&lt;5 mm), but weak in the PFJ with non-narrowing (⩾5 mm).
A comparative study of the major glycoprotein isolated from normal and neoplastic gastric mucosa
Authors: J. Schrager, M. D. G. Oates
Journal: Gut (1973)

The isolation and composition of glycoproteins from mucosae of normal stomachs, of stomachs with gastric ulcer, and of stomachs with carcinoma is described. The glycoproteins from the mucosae of normal stomachs and with gastric ulcer showed virtually the same carbohydrate and amino acid content as the principal gastric glycoprotein isolated from gastric aspirates. They all revealed a common basic carbohydrate composition: galactose, fucose, glucosamine, and galactosamine were present in approximate molar ratios of 4:3:3:1. The results suggest that the glycoproteins isolated from gastric aspirates from normal and neoplastic gastric mucosae share a number of structural features: (1) a protein core with a characteristic amino acid composition; (2) the range of sugars forming the carbohydrate side chains; (3) galactosamine approximately equimolar with the sum of threonine and serine; (4) galactose approximately equimolar with the sum of glucosamine and galactosamine; (5) absence of mannose; (6) a high carbohydrate content (80-85%); and (7) blood group activity. The neoplastic glycoproteins differed from the normal glycoproteins in that the quantitative relationships of the carbohydrate components of the neoplastic glycoproteins showed variations dividing the extracts investigated into groups, each group with a distinctive and constant carbohydrate composition. The blood group specificity of 15 out of 24 cases investigated differed from that of the hosts9 red cells.
Multimerin-1 (<i>MMRN1</i>) as Novel Adverse Marker in Pediatric Acute Myeloid Leukemia: A Report from the Children's Oncology Group
Authors: George S. Laszlo, Todd A. Alonzo, Chelsea J. Gudgeon, Kimberly H. Harrington, Robert B. Gerbing, Yi-Cheng Wang, Rhonda E. Ries, Susana C. Raimondi, Betsy A. Hirsch, Alan S. Gamis, Soheil Meshinchi, Roland B. Walter
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Exploratory gene expression array analyses suggested multimerin-1 (MMRN1) to be a predictive biomarker in acute myelogenous leukemia (AML). Following up on these studies, we evaluated the role of MMRN1 expression as outcome predictor in two recent Children's Oncology Group trials. Experimental Design: We retrospectively quantified MMRN1 expression in 183 participants of AAML03P1 and 750 participants of AAML0531 by reverse-transcriptase PCR and correlated expression levels with disease characteristics and clinical outcome. Results: In AAML03P1, the highest quartile of MMRN1 expression (expression ≥0.5 relative to β-glucuronidase; n = 45) was associated with inferior event-free survival (EFS; P &amp;lt; 0.002) and higher relapse risk (P &amp;lt; 0.004). In AAML0531, in which we quantified MMRN1 mRNA for validation, patients with relative MMRN1 expression ≥0.5 (n = 160) less likely achieved remission (67% vs. 77%, P = 0.006), and more frequently had minimal residual disease (43% vs. 24%, P = 0.001) after one induction course. They had inferior overall survival (OS; 44% ± 9% vs. 69% ± 4% at 5 years; P &amp;lt; 0.001) and EFS (32% ± 8% vs. 54% ± 4% at 5 years; P &amp;lt; 0.001) and higher relapse risk (57% ± 10% vs. 35% ± 5% at 5 years; P &amp;lt; 0.001). These differences were partly attributable to the fact that patients with high MMRN1 expression less likely had cytogenetic/molecular low-risk disease (P &amp;lt; 0.001) than those with low MMRN1 expression. Nevertheless, after multivariable adjustment, high MMRN1 expression remained statistically significantly associated with shorter OS (HR, 1.57; 95% confidence interval, 1.17–2.12; P = 0.003) and EFS (HR, 1.34; 1.04–1.73; P = 0.025), and higher relapse risk (HR, 1.40; 1.01–1.94; P = 0.044). Conclusions: Together, our studies identify MMRN1 expression as a novel biomarker that may refine AML risk stratification. Clin Cancer Res; 21(14); 3187–95. ©2015 AACR.
Health Care–Associated Invasive MRSA Infections, 2005-2008
Authors: Alexander J. Kallen
Journal: JAMA (2010)

Methicillin-resistant Staphylococcus aureus (MRSA) is a pathogen of public health importance; MRSA prevention programs that may affect MRSA transmission and infection are increasingly common in health care settings. Whether there have been changes in MRSA infection incidence as these programs become established is unknown; however, recent data have shown that rates of MRSA bloodstream infections (BSIs) in intensive care units are decreasing.To describe changes in rates of invasive health care-associated MRSA infections from 2005 through 2008 among residents of 9 US metropolitan areas.Active, population-based surveillance for invasive MRSA in 9 metropolitan areas covering a population of approximately 15 million persons. All reports of laboratory-identified episodes of invasive (from a normally sterile body site) MRSA infections from 2005 through 2008 were evaluated and classified based on the setting of the positive culture and the presence or absence of health care exposures. Health care-associated infections (ie, hospital-onset and health care-associated community-onset), which made up 82% of the total infections, were included in this analysis.Change in incidence of invasive health care-associated MRSA infections and health care-associated MRSA BSIs using population of the catchment area as the denominator.From 2005 through 2008, there were 21,503 episodes of invasive MRSA infection; 17,508 were health care associated. Of these, 15,458 were MRSA BSIs. The incidence rate of hospital-onset invasive MRSA infections was 1.02 per 10,000 population in 2005 and decreased 9.4% per year (95% confidence interval [CI], 14.7% to 3.8%; P = .005), and the incidence of health care-associated community-onset infections was 2.20 per 10,000 population in 2005 and decreased 5.7% per year (95% CI, 9.7% to 1.6%; P = .01). The decrease was most prominent for the subset of infections with BSIs (hospital-onset: -11.2%; 95% CI -15.9% to -6.3%; health care-associated community-onset: -6.6%; 95% CI -9.5% to -3.7%).Over the 4-year period from 2005 through 2008 in 9 diverse metropolitan areas, rates of invasive health care-associated MRSA infections decreased among patients with health care-associated infections that began in the community and also decreased among those with hospital-onset invasive disease.
Global Fund overwhelmed by requests
Authors: F. Fleck
Journal: BMJ (2002)

The Global Fund, hailed as a major step in the fight against AIDS, tuberculosis, and malaria when it was launched last year, has been overwhelmed with applications from developing countries.

A key project of United Nations' secretary general Kofi Annan, the fund has received pledges from developed countries and private donors to the value of $1.92bn (£1.35bn; €2.20bn), of which $700-800m will be disbursed this year and the rest in 2003.

But developing countries are asking for $1.15bn—much …
Possible differences in hematological status between junior and elite female volleyball players
Authors: R Milić, M Dopsaj
Journal: British Journal of Sports Medicine (2011)

Background Iron deficiency anaemia and iron deficiency without anemia have debilitating effects on athletic performance due to decreased work capacity and impaired cognition. Objective The main goal of this research was to identify possible differences in haematological status between junior and elite female volleyball players. Subjects 38 female volleyball players belonging to Junior (J) and Elite (E) Serbian and Slovenian national volleyball teams were recruited for the study. The average age of 18 E athletes was 23.8±2.9 years, body height 177.9±9.5 cm, body weight 68.9±7.9 kg and their body mass index (BMI) was 21.7±0.9 kg/m 2 . Training experience was 12.0±3.2 years and training load in the last micro cycle was 18.4±1.2 h per week. The age of 20 J athletes was 16.9±1.2 years, body height 177.4±5.4 cm, body weight 65.2±3.5 kg and the mean BMI was 20.8±1.4 kg/m 2 . Training experience was 6.4±1.4 years and training load in the last micro cycle was 15.7±1.6 h per week. Methods Blood collection was performed between 7 and 8 am at the beginning of the pre-competitive training period after a 12-h overnight fast. Venous blood was collected into evacuated tubes (Vacutainer, Becton Dickinson, USA) from the antecubital vein with minimal stasis. Blood analyses were performed on the instrument Advia 120 (Siemens, Tarrytown, USA), appropriately calibrated and controlled. 14 parameters were taken into account: RBC, Hb, Hct, Ret_abs and Ret (%), erythrocyte index (MCV, MCH, MCHC), RDW, TIBC, iron, ferritin, transferin saturation, soluble transferring receptor (s-TfR). Descriptive statistics and multivariate analysis of variance were employed to investigate differences between the two groups. The result was considered significant when p&lt;0.05. SPSS 17.0 statistical package were used. Results Statistical analysis showed significant differences (p&lt;0.05) between (J) and (E) female volleyball players in five parameters from performed blood analyses (RBC, Hct, MCHC, TIBC, ferritin) with lower absolute values in the elite group. Conclusions The current study is the first to demonstrate differences in the haematological status between junior and elite female volleyball players, the underlying reasons for which may include differences in training experience and training load.
Long-term follow-up of lenalidomide in relapsed/refractory mantle cell lymphoma: subset analysis of the NHL-003 study
Authors: P.L. Zinzani, J.M. Vose, M.S. Czuczman, C.B. Reeder, C. Haioun, J. Polikoff, H. Tilly, L. Zhang, K. Prandi, J. Li, T.E. Witzig
Journal: Annals of Oncology (2013)

Mantle cell lymphoma (MCL) is an uncommon type of non-Hodgkin lymphoma with poor overall prognosis, requiring the development of new therapies. Lenalidomide is an immunomodulatory agent demonstrating antitumor and antiproliferative effects in MCL. We report results from a long-term subset analysis of 57 patients with relapsed/refractory MCL from the NHL-003 phase II multicenter study of single-agent lenalidomide in patients with aggressive lymphoma
NI-48 * COMPARISON OF DTI AND 11C-METHIONINE PET FOCUSING ON THEIR PREDICTIVE VALUES OF TUMOR CELL DENSITY IN GLIOMAS
Authors: M. Kinoshita, H. Arita, N. Kagawa, Y. Watanabe, J. Hatazawa, N. Hashimoto, T. Yoshimine
Journal: Neuro-Oncology (2014)

Although precise identification of the extension within the brain and tumor core characterization of glioma is crucial for successful treatment, imaging and predicting tumor cell density or tumor cell invasion is challenging. Positron emission tomography (PET) based and magnetic resonance imaging (MRI) have been explored extensively to meet this purpose. In this research, the authors have compared diffusion tensor imaging (DTI) and 11C-methionine PET in terms of tumor cell density prediction by use of 98 stereotactically sampled glioma tissues from 37 patients (low grade 5 and high grade 32). Relative values of ADC (rADC) and FA (rFA) compared to normal appearing white matter (NAWM) and tumor to normal ratio of 11C-methionine PET (MET-TNR) were measured at locations where the tissues were sampled and subsequently those values were compared to tumor cell densities within the tissues. Tumor cell density showed a statistically significant positive correlation with MET-TNR (p < 0.0001, R2 = 0.43) and negative correlation with rADC (p = 0.0096, R2 = 0.09), while rFA did not correlate with tumor cell density. When multiple regression analysis was applied for MET-TNR and rADC in order to predict tumor cell density, MET-TNR was the solo statistically significant factor for tumor cell density prediction (MET-TNR: p < 0.0001, rADC: p = 0.06). These results confirm that 11C-methionine PET is a much more reliable imaging modality for glioma imaging in terms of tumor cell density prediction compared to DTI. Although extensive research is ongoing for glioma characterization using diffusion MR based imaging, it should be reminded that PET using amino acid tracers could be much better imaging modalities for this purpose. It could also be suggested that PET by amino acid tracers should be incorporated as one of the “standard imaging modalities” for glioma assessment.
Anti-TNF therapies and pregnancy: outcome of 130 pregnancies in the British Society for Rheumatology Biologics Register
Authors: S. M. M. Verstappen, Y. King, K. D. Watson, D. P. M. Symmons, K. L. Hyrich
Journal: Annals of the Rheumatic Diseases (2011)

The British Society for Rheumatology Biologics Register (BSRBR) has collected data on adverse events including pregnancies in patients with rheumatoid arthritis treated with anti-tumour necrosis factor (anti-TNF) therapy. The purpose of this report is to summarise the pregnancy outcomes in women treated with anti-TNF in the BSRBR.Patients were categorised according to anti-TNF exposure as follows: (1) exposure to anti-TNF and to methotrexate (MTX) and/or leflunomide (LEF) at conception (n=21 pregnancies); (2) exposure to anti-TNF at conception (n=50); (3) exposure to anti-TNF prior to conception (n=59); (4) no exposure to anti-TNF (control group; n=10).Eighty-eight live births in a total of 130 pregnancies were reported in patients who received anti-TNF before or during pregnancy. The rate of spontaneous abortion was highest among patients exposed to anti-TNF at the time of conception (with MTX/LEF 33% and without MTX/LEF 24%). This compared with 17% spontaneous abortions in those with prior exposure to anti-TNF and 10% spontaneous abortions in the control group. Ten terminations were performed.Although the results to date have been promising, no firm conclusions can be drawn about the safety of anti-TNF during pregnancy and, without further evidence, guidelines which suggest these drugs should be avoided at the time of conception cannot yet be changed.
Endothelial dysfunction of conduit arteries in insulin-dependent diabetes mellitus without microalbuminuria
Authors: J Lekakis
Journal: Cardiovascular Research (1997)

Objective: Previous studies have shown that endothelial dysfunction, an early sign of atherosclerosis, occurs in animal models of diabetes mellitus and in resistance vessels of patients with insulin-dependent diabetes. In the present study we examined whether young patients with insulin-dependent diabetes without microalbuminuria present abnormal endothelial function of large peripheral arteries. Methods: Twenty-six patients with insulin-dependent diabetes without microalbuminuria were compared with 26 normal controls and 5 patients with insulin-dependent diabetes with microalbuminuria. Brachial artery diameter was measured at rest, during reactive hyperaemic flow (endothelium-dependent dilatation) and after sublingual isosorbide dinitrate (endothelium-independent dilatation). Results: Baseline artery diameter and flow as well as the degree of reactive hyperaemia were similar in all groups compared to controls. Flow-mediated dilatation was lower in patients with diabetes without microalbuminuria (5.8±7 vs 11±7%, P=0.01) as well as in patients with diabetes without microalbuminuria (0.75±2.5 vs 11±7%, P=0.003); nitrate-induced dilatation was normal in patients without microalbuminuria and attenuated in patients with microalbuminuria. In the group of diabetes patients without microalbuminuria, those with disease duration >10 years and HbA1c >6% had the worse endothelial function. Conclusions: Our results demonstrate that endothelial dysfunction of conduit arteries can be detected in patients with insulin-dependent diabetes mellitus without microalbuminuria, probably contributing to the high prevalence of atherosclerosis in these patients.
The Sequential Role of Lymphotoxin and B Cells in the Development of Splenic Follicles
Authors: Mercedes Gonzalez, Fabienne Mackay, Jeffrey L. Browning, Marie H. Kosco-Vilbois, Randolph J. Noelle
Journal: The Journal of Experimental Medicine (1998)

The transfer of lymphocytes into severe combined immunodeficiency (SCID) mice induces a series of histological changes in the spleen, including the appearance of mature follicular dendritic cells (FDCs). Studies were undertaken to clarify the role of lymphotoxin (LT) in this process. The results show that SCID mice have a small and partially differentiated white pulp containing marginal zone and interdigitating dendritic cells, but lacking FDCs. Transferred spleen cells can segregate into T and B cell areas shortly after their injection to SCID mice. This ability is dependent on signaling through LT-β receptor (LT-βR), since blocking ligand–receptor interaction in recipient SCID mice ablates the capacity of the transferred cells to segregate. A week after lymphocyte transfer, host-derived FDCs appeared in the reconstituted SCID mice. This induction of FDCs is dependent on LT-βR signaling by B cells since LT-α−/− B cells are incapable of inducing development of FDCs in SCID mice, even after cotransfer of LT-α+/+ T cells. Therefore, LT plays at least two discrete roles in splenic organization. First, it appears that LT induces the differentiation of the white pulp to create sites for lymphocyte segregation. Second, LT expression by B cells drives the maturation of FDCs and the organization of B cell follicles.
Long-Term Treatment With a Specific Rho-Kinase Inhibitor Suppresses Cardiac Allograft Vasculopathy in Mice
Authors: Tsuyoshi Hattori, Hiroaki Shimokawa, Midoriko Higashi, Junko Hiroki, Yasushi Mukai, Kozo Kaibuchi, Akira Takeshita
Journal: Circulation Research (2003)

Cardiac allograft vasculopathy (CAV) continues to be a major cause of late graft failure after cardiac transplantation. We have demonstrated that Rho-kinase, an effector of the small GTPase Rho, plays an important role in the pathogenesis of arteriosclerosis. In this study, we examined whether the Rho-kinase–mediated pathway is also involved in the pathogenesis of CAV using a specific Rho-kinase inhibitor and a dominant-negative Rho-kinase. Hearts from AKR mice were heterotopically transplanted to C3H/He (allograft) or AKR mice (isograft), and the effects of long-term oral treatment with fasudil, which is metabolized to a specific Rho-kinase inhibitor hydroxyfasudil, on CAV were examined at 2 and 4 weeks after the transplantation. Coronary remodeling in the allografts characterized by intimal thickening and perivascular fibrosis was dose-dependently suppressed in the fasudil group compared with the control group ( P &lt;0.01, n=9 to 10). The inhibitory effects of hydroxyfasudil were mimicked by in vivo gene transfer of dominant-negative Rho-kinase ( P &lt;0.05, n=4). Among the proinflammatory cytokines examined, those of macrophage migration inhibitory factor, interferon-γ, and transforming growth factor-β1 were upregulated in the control group and were dose-dependently inhibited in the fasudil group ( P &lt;0.01, n=5). Vascular inflammation in the allografts, as evidenced by accumulation of inflammatory cells (macrophages and T cells), was also significantly inhibited in the fasudil group ( P &lt;0.05, n=5 to 10). These results indicate that long-term treatment with fasudil suppresses CAV in mice, suggesting that Rho-kinase is an important therapeutic target for the prevention of CAV.