tbuckley/cabot-search huggingface dataset:
Highly Sensitive Detection of Melanoma at an Early Stage Based on the Increased Serum Secreted Protein Acidic and Rich in Cysteine and Glypican-3 Levels
Authors: Yoshiaki Ikuta, Tetsuya Nakatsura, Toshiro Kageshita, Satoshi Fukushima, Shosuke Ito, Kazumasa Wakamatsu, Hideo Baba, Yasuharu Nishimura
Journal: Clinical Cancer Research (2005)

Abstract Purpose: There are no available tumor markers detecting primary melanoma at an early stage. The identification of such serum markers would be of significant benefit for an early diagnosis of melanoma. We recently identified glypican-3 (GPC3) as a novel tumor marker but could diagnose only 40% of melanomas. Thereby, we focused out attention on secreted protein acidic and rich in cysteine (SPARC) overexpressed in melanoma as another candidate for tumor marker. Experimental Design: Secreted SPARC protein was quantified using ELISA in the sera from 109 melanoma patients, five patients with large congenital melanocytic nevus, 61 age-matched healthy donors, and 13 disease-free patients after undergoing a surgical removal. We also quantified GPC3 and 5-S-cysteinyldopa in the same serum samples and compared these markers for their diagnostic value. Results: The serum SPARC concentrations in melanoma patients were greater than those in healthy donors (P = 0.001). When we fixed a cutoff value at the mean concentration plus 2 SD of the healthy donors, the serum SPARC was found to have increased in the sera of 36 of the 109 (33%) melanoma patients, whereas there were three (4.9%) false-positive cases of 61 healthy donors. Surprisingly, 19 of 36 patients showing increased SPARC levels were in stages 0 to II. The serum SPARC level decreased under the cutoff level in 10 of 13 patients after surgical removal. Using SPARC and GPC3 in combination thus enabled us to diagnose 47 of 75 (66.2%) melanoma patients at an early stage (0-II). Conclusions: SPARC or its combination with GPC3 is thus considered a potentially useful tumor marker, especially for melanoma at an early stage.
Metformin for the Treatment of the Polycystic Ovary Syndrome
Authors: John E. Nestler
Journal: New England Journal of Medicine (2008)

A 23-year-old woman with the polycystic ovary syndrome presents for evaluation and possible treatment. She has a family history of diabetes, is obese, and has impaired glucose tolerance. Metformin therapy is recommended. Metformin increases insulin sensitivity and may reduce the risk of diabetes. In the polycystic ovary syndrome, long-term metformin treatment may increase ovulation, improve menstrual cyclicity, and reduce serum androgen levels.
Cytogenetic and molecular predictors of response in patients with myeloid malignancies without del[5q] treated with lenalidomide
Authors: Yuka Sugimoto, Mikkael A Sekeres, Hideki Makishima, Fabiola Traina, Valeria Visconte, Anna Jankowska, Andres Jerez, Hadrian Szpurka, Christine L O'Keefe, Kathryn Guinta, Manuel Afable, Ramon Tiu, Kathy L McGraw, Alan F List, Jaroslaw Maciejewski
Journal: Journal of Hematology & Oncology (2012)

Abstract Background While lenalidomide (LEN) shows high efficacy in myelodysplastic syndromes (MDS) with del[5q], responses can be also seen in patients presenting without del[5q]. We hypothesized that improved detection of chromosomal abnormalities with new karyotyping tools may better predict response to LEN. Design and methods We have studied clinical, molecular and cytogenetic features of 42 patients with MDS, myeloproliferative neoplasms (MPN), MDS/MPN overlap syndromes and secondary acute myeloid leukemia (sAML) without del[5q] by metaphase cytogenetics (MC) who underwent therapy with LEN. Results Fluorescence in situ hybridization (FISH) or single nucleotide polymorphism array (SNP-A)-based karyotyping marginally increased the diagnostic yield over MC, detecting 2/42 (4.8%) additional cases with del[5q], one of whom were responded to LEN. Responses were more often observed in patients with a normal karyotype by MC (60% vs abnormal MC; 17%, p = .08) and those with gain of chromosome 8 material by either of all 3 karyotyping methods (83% vs all other chromosomal abnormalities; 44% p = .11). However, 5 out of those 6 patients received combined LEN/AZA therapy and it may also suggest those with gain of chromosome 8 material respond well to AZA. The addition of FISH or SNP-A did not improve the predictive value of normal cytogenetics by MC. Mutational analysis of TET2, UTX, CBL, EZH2, ASXL1, TP53, RAS, IDH1/2 , and DNMT-3A was performed on 21 of 41 patients, and revealed 13 mutations in 11 patients, but did not show any molecular markers of responsiveness to LEN. Conclusions Normal karyotype and gain of chromosome 8 material was predictive of response to LEN in non-del[5q] patients with myeloid malignancies.
Prevalence and determinants of one month hand pain and hand related disability in the elderly (Rotterdam study)
Authors: S Dahaghin
Journal: Annals of the Rheumatic Diseases (2004)

To study the prevalence of hand pain and hand disability in an open population, and the contribution of their potential determinants.Baseline data were used from 7983 participants in the Rotterdam study (a population based study in people aged > or =55 years). A home interview was used to determine the presence of hand pain during the previous month, rheumatoid arthritis, osteoarthritis in any joint, diabetes, stroke, thyroid disease, neck/shoulder pain, gout, history of fracture in the past five years, and Parkinson's disease, as well as age, sex, and occupation. Hand disability was defined as the mean score of eight questions related to hand function. Body mass index was measured and hand x rays were taken.The one month period prevalence of hand pain was 16.9%. The prevalence of hand disability was 13.6%. In univariate analysis for hand pain, rheumatoid arthritis had the highest explained variance (R(2)) and odds ratio. For hand disability, aging showed the highest explained variance and Parkinson's disease had the highest odds ratio. All determinants together showed an explained variance of 19.8% for hand pain and 25.2% for hand disability. In multivariate analysis, positive radiographic hand osteoarthritis was a poor explanation for hand pain (R(2) = 0.5%) or hand disability (R(2) = 0).The contribution of available potential determinants in this study was about 20% for hand pain and 25% for hand disability in an unselected population of elderly people. Thus a greater part of hand pain/hand disability remains unexplained.
Defining erosive disease typical of RA in the light of the ACR/EULAR 2010 criteria for rheumatoid arthritis; results of the data driven phase
Authors: Rachel Knevel, Cédric Lukas, Désirée van der Heijde, Nathalie Rincheval, Bernard Combe, Annette H M van der Helm-van Mil
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> According to the 2010 criteria, rheumatoid arthritis (RA) can be classified in the presence of ≥6 points on the criteria or 'typical' erosive disease. RA-specific erosiveness however has not been defined yet. This study reports the results of the data driven phase of a European League Against Rheumatism (EULAR) taskforce aiming to define RA-specific erosiveness. <h3>Methods</h3> Baseline radiographs of hands and feet of 980 Dutch and 811 French early arthritis patients were studied on the number and site of erosive joints. Test characteristics were determined, with the outcome measures being initiation of methotrexate (MTX) therapy or any disease modifying antirheumatic drug (DMARD) therapy within the first year of disease and arthritis persistency over 5 years. Analyses were repeated in the patients with &lt;6 points on the American College of Rheumatology/EULAR 2010 criteria. <h3>Results</h3> In both cohorts comparable test characteristics were observed for the outcomes MTX therapy, any DMARD therapy and arthritis persistency. Test characteristics were not influenced by the site of erosiveness. The specificity observed was &gt;50% for ≥1 erosive joint, &gt;80% for ≥3 erosive joints and &gt;90% for ≥5 erosive joints. When analysing the patients not fulfilling the 2010 criteria (n=308 and 149), specificity was &gt;60% for ≥1 erosive joint, &gt;90% for ≥3 erosive joints and &gt;95% for ≥5 erosive joints. Few of these patients fulfilled the radiological criterion; 27–36 patients had ≥3 erosive joints and 13–14 patients had ≥5 erosive joints. <h3>Conclusions</h3> RA-specific erosiveness can be defined with high specificity at several cut-offs for the number of erosive joints in two independent cohorts with multiple different outcomes. The final radiological criterion will be established in the next phase.
Behcet's disease and pregnancy.
Authors: M Hamza, M Elleuch, A Zribi
Journal: Annals of the Rheumatic Diseases (1988)

Behqet's disease and pregnancy SIR, At the 3rd International Conference on Behcet's Disease it was proposed that hormonal factors may influence the pathogenesis of this disease.'A variable influence of pregnancy has been reported.Madkour and Kudwah reported exacerbation of mucocutaneous and arthritic manifestations in four women,2 and Plouvier and Devulder,3 Ferraro et al,4 and Suchenwirths have reported remission during pregnancies.Behqet's disease did not influence any pregnancy, there being no abortions, prematurity, or perinatal deaths.
Comparative Genomic Hybridization Profiles in Human BRCA1 and BRCA2 Breast Tumors Highlight Differential Sets of Genomic Aberrations
Authors: Erik H. van Beers, Tibor van Welsem, Lodewyk F.A. Wessels, Yunlei Li, Rogier A. Oldenburg, Peter Devilee, Cees J. Cornelisse, Senno Verhoef, Frans B.L. Hogervorst, Laura J. van't Veer, Petra M. Nederlof
Journal: Cancer Research (2005)

BRCA1 or BRCA2 germline mutations cause approximately 30% of breast cancers within high-risk families. This represents 5% of total breast cancer incidence. Although BRCA1 and BRCA2 are both implicated in DNA repair and genome stability, it is unknown whether BRCA1 and BRCA2 are associated with similar or distinct diseases. In a previous study we reported that BRCA1-related breast carcinomas show a distinct genomic profile as determined by comparative genomic hybridization (CGH). We now hypothesize that, if functionally equivalent, mutations in BRCA1 and BRCA2 would result in similar genomic profiles in tumors. Here we report the chromosomal gains and losses as measured by CGH in 25 BRCA2-associated breast tumors and compared them with our existing 36 BRCA1 and 30 control profiles. We compared all chromosomal regions and determined the regions of differential gain or loss between tumor classes and controls. BRCA2 and control tumors have very similar genomic profiles. As a consequence, and in contrast to BRCA1-associated tumors, CGH profiles from BRCA2-associated tumors could not be distinguished from control tumors using the classification methodology as we have developed before. The largest number of significant differences existed between BRCA1 and controls, followed by BRCA1 compared with BRCA2, suggesting different tumor development pathways for BRCA1 and BRCA2.
High-Resolution Analysis of Chromosomal Breakpoints and Genomic Instability Identifies <i>PTPRD</i> as a Candidate Tumor Suppressor Gene in Neuroblastoma
Authors: Raymond L. Stallings, Prakash Nair, John M. Maris, Daniel Catchpoole, Michael McDermott, Anne O'Meara, Fin Breatnach
Journal: Cancer Research (2006)

Abstract Although neuroblastoma is characterized by numerous recurrent, large-scale chromosomal imbalances, the genes targeted by such imbalances have remained elusive. We have applied whole-genome oligonucleotide array comparative genomic hybridization (median probe spacing 6 kb) to 56 neuroblastoma tumors and cell lines to identify genes involved with disease pathogenesis. This set of tumors was selected for having either 11q loss or MYCN amplification, abnormalities that define the two most common genetic subtypes of metastatic neuroblastoma. Our analyses have permitted us to map large-scale chromosomal imbalances and high-level amplifications at exon-level resolution and to identify novel microdeletions and duplications. Chromosomal breakpoints (n = 467) generating imbalances &amp;gt;2 Mb were mapped to intervals ranging between 6 and 50 kb in size, providing substantial information on each abnormality. For example, breakpoints leading to large-scale hemizygous loss of chromosome 11q were highly clustered and preferentially associated with segmental duplications. High-level amplifications of MYCN were extremely complex, often resulting in a series of discontinuous regions of amplification. Imbalances (n = 540) &amp;lt;2 Mb long were also detected. Although the majority (78%) of these imbalances mapped to segmentally duplicated regions and primarily reflect constitutional copy number polymorphisms, many subtle imbalances were detected that are likely somatically acquired alterations and include genes involved with tumorigenesis, apoptosis, or neural cell differentiation. The most frequent microdeletion involved the PTPRD locus, indicating a possible tumor suppressor function for this gene. (Cancer Res 2006; 66(7): 3673-80)
PPARγ Agonists Ameliorate Endothelial Cell Activation via Inhibition of Diacylglycerol–Protein Kinase C Signaling Pathway
Authors: Emily Verrier, Lijun Wang, Carol Wadham, Nathaniel Albanese, Chris Hahn, Jennifer R. Gamble, V. Krishna K. Chatterjee, Mathew A. Vadas, Pu Xia
Journal: Circulation Research (2004)

Subject- Peroxisome proliferator-activated receptor (PPAR)-gamma agonists are emerging as potential protectors against inflammatory cardiovascular diseases including atherosclerosis and diabetic complications. However, their molecular mechanism of action within vasculature remains unclear. We report here that PPARgamma agonists, thiazolidinedione class drugs (TZDs), or 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2) were capable of activating diacylglycerol (DAG) kinase (DGK), resulting in attenuation of DAG levels and inhibition of protein kinase C (PKC) activation. The PPARgamma agonist-induced DGK was completely blocked by a dominant-negative mutant of PPARgamma, indicating an essential receptor-dependent action. Importantly, the suppression of DAG-PKC signaling pathway was functional linkage to the anti-inflammatory properties of PPARgamma agonists in endothelial cells (EC), characterized by the inhibition of proinflammatory adhesion molecule expression and adherence of monocytes to the activated EC induced by high glucose. These findings thus demonstrate a novel molecular action of PPARgamma agonists to suppress the DAG-PKC signaling pathway via upregulation of an endogenous attenuator, DGK.
Effect of α<sub>4</sub>-Integrin Blockade on CD4<sup>+</sup>Cell-driven Late Airway Responses in the Rat
Authors: DAVID RAMOS-BARBÓN, MASARU SUZUKI, RAME TAHA, SOPHIE MOLET, THOMAS B. ISSEKUTZ, QUTAYBA HAMID, JAMES G. MARTIN
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

The blockade of α4 integrins with a monoclonal antibody (TA-2) decreases late airway responses (LR) in ovalbumin (OVA)-sensitized and challenged rats. In this study, we used a model of CD4+ cell-driven LR to test the hypothesis that α4-integrin blockade involves interference with T-cell activation in the inhibition of LR. Purified CD4+ cells from OVA-sensitized rats were transferred to unsensitized recipients, which received either TA-2 or a control antibody (cAb), and were OVA-challenged. A sham-challenged group was also studied. LR, calculated from pulmonary resistance after challenge, were reduced in the TA-2 group compared with the cAb group (p = 0.015). Total cell counts, macrophages, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL), and CD3+ cells in airway sections, were unaffected. The cAb group had higher numbers of cells expressing interleukin-5 (IL-5) mRNA (55.2 ± 3.39 cells/1,000, mean ± SEM) and major basic protein (MBP) (6.2 ± 0.4/100 cells) in bronchoalveolar lavage (BAL), than the TA-2 group (25.37 ± 2.41 IL-5+ and 2.7 ± 0.2 MBP+) and the sham group (12.37 ± 0.96 IL-5+, 1.7 ± 0.1 MBP+). Interferon gamma (IFN- γ ) mRNA+ cells were downregulated in both OVA-challenged groups, compared with the sham group. Our results suggest that the attenuation of LR and eosinophilia by α4-integrin blockade may involve interference with CD4+ cell activation and IL-5 expression.
Association between markers of emphysema and more severe chronic obstructive pulmonary disease
Authors: P Boschetto, S Quintavalle, E Zeni, S Leprotti, A Potena, L Ballerin, A Papi, G Palladini, M Luisetti, L Annovazzi, P Iadarola, E De Rosa, L M Fabbri, C E Mapp
Journal: Thorax (2006)

<b>Background:</b> The predominant emphysema phenotype is associated with more severe airflow limitation in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate whether COPD patients, with or without emphysema quantitatively confirmed by high resolution computed tomography (HRCT), have different COPD severity as assessed by the BODE index (body mass index, airflow obstruction, dyspnoea, exercise performance) and inspiratory capacity to total lung capacity ratio (IC/TLC), and by different biological markers of lung parenchymal destruction. <b>Methods:</b> Twenty six outpatients with COPD and eight healthy non-smokers were examined. Each subject underwent HRCT scanning, pulmonary function tests, cell counts, and measurements of neutrophil elastase, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinase (TIMP)-1 in induced sputum, as well as measurement of desmosine, a marker of elastin degradation in urine, plasma and sputum. <b>Results:</b> Patients with HRCT confirmed emphysema had a higher BODE index and lower IC/TLC ratio than subjects without HRCT confirmed emphysema and controls. Forced expiratory volume in 1 second (FEV<sub>1</sub>), FEV<sub>1</sub>/forced vital capacity ratio, and carbon monoxide transfer coefficient were lower, whereas the number of eosinophils, MMP-9, and the MMP-9/TIMP-1 ratio in sputum were higher in patients with emphysema. In COPD patients the number of sputum eosinophils was the biological variable that correlated positively with the HRCT score of emphysema (p = 0.04). <b>Conclusions:</b> These results suggest that COPD associated with HRCT confirmed emphysema is characterised by more severe lung function impairment, more intense airway inflammation and, possibly, more serious systemic dysfunction than COPD not associated with HRCT confirmed emphysema.
Acute variceal bleeding in a man with coeliac disease
Authors: Crispin Okwiri Musumba, Fiona Campbell, Sreedhar Subramanian, Paul Richardson, Howard L Smart
Journal: Gut (2012)

Although the main regulators of leukocyte trafficking are chemokines, another family of chemotactic agents is cyclophilins. Intracellular cyclophilins function as peptidyl-prolyl <i>cis-trans</i> isomerases and are targets of the immunosuppressive drug cyclosporine A (CsA). Cyclophilins can also be secreted in response to stress factors, with elevated levels of extracellular cyclophilins detected in several inflammatory diseases. Extracellular cyclophilins are known to have potent chemotactic properties, suggesting that they might contribute to inflammatory responses by recruiting leukocytes into tissues. The objective of the present study was to determine the impact of blocking cyclophilin activity using a cell-impermeable derivative of CsA to specifically target extracellular pools of cyclophilins. In this study, we show that treatment with this compound in a mouse model of allergic lung inflammation demonstrates up to 80% reduction in inflammation, directly inhibits the recruitment of Ag-specific CD4<sup>+</sup> T cells, and works equally well when delivered at 100-fold lower doses directly to the airways. Our findings suggest that cell-impermeable analogs of CsA can effectively reduce inflammatory responses by targeting leukocyte recruitment mediated by extracellular cyclophilins. Specifically blocking the extracellular functions of cyclophilins may provide an approach for inhibiting the recruitment of one of the principal immune regulators of allergic lung inflammation, Ag-specific CD4<sup>+</sup> T cells, into inflamed airways and lungs.
153Samarium-EDTMP administration followed by hematopoietic stem cell support for bone metastases in osteosarcoma patients
Authors: M. Berger, G. Grignani, A. Giostra, S. Ferrari, V. Ferraresi, A. Tamburini, G. Cefalo, F. Carnevale-Schianca, E. Vassallo, P. Picci, M. Pagano, M. Aglietta, R.E. Pellerito, F. Fagioli
Journal: Annals of Oncology (2011)
Prevalence of Gestational Diabetes Mellitus Detected by the National Diabetes Data Group or the Carpenter and Coustan Plasma Glucose Thresholds
Authors: Assiamira Ferrara, Monique M. Hedderson, Charles P. Quesenberry, Joseph V. Selby
Journal: Diabetes Care (2002)

OBJECTIVE—In 2000, the American Diabetes Association proposed the adoption of the Carpenter and Coustan criteria for diagnosis of gestational diabetes mellitus (GDM). The Carpenter and Coustan cutoffs are lower than the previously recommended National Diabetes Data Group (NDDG) values and would result in higher prevalence of GDM. Our aim is to estimate the magnitude of change in prevalence of GDM using the Carpenter and Coustan thresholds as compared with the NDDG thresholds by age and ethnicity. RESEARCH DESIGN AND METHODS—Cross-sectional study of 28,330 women aged 14–49 years who gave birth in 1996 and were members of the Northern California Kaiser Permanente Medical Care Program. Age, ethnicity, screening, and diagnostic test results were assessed from computerized hospitalization and laboratory systems. RESULTS—A total of 26,481 (94%) women were screened using a 50-g, 1-h oral glucose tolerance test, and 4,190 women underwent a diagnostic 100-g, 3-h oral glucose tolerance test after an abnormal screening. Overall, the GDM prevalence among screened women was 3.2% (95% CI 3.0–3.4) by NDDG and 4.8% (95% CI 4.5–5.1) by Carpenter and Coustan criteria, and based on either threshold, it increased with age (P &amp;lt; 0.001). The age-adjusted GDM prevalence by NDDG and Carpenter and Coustan criteria, respectively, was 5.0 and 7.4% in Asians, 3.9 and 5.6% in Hispanics, 3.0 and 4.0% in African-Americans, and 2.4 and 3.8% in whites. Proportional increments were larger in women aged &amp;lt;25 years (70%) and in whites (58%). CONCLUSIONS—The prevalence of GDM increased, on average, by 50% with use of the Carpenter and Coustan thresholds. Relative increments were greater in low-risk age and ethnic groups. This information would be useful for clinical settings in predicting cost of GDM based on demographic characteristics of the population.
Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: randomised trial—the Losartan Heart Failure Survival Study ELITE II
Authors: Bertram Pitt, Philip A Poole-Wilson, Robert Segal, Felipe A Martinez, Kenneth Dickstein, A John Camm, Marvin A Konstam, Günter Riegger, George H Klinger, James Neaton, Divakar Sharma, Balasamy Thiyagarajan
Journal: The Lancet (2000)