tbuckley/cabot-search huggingface dataset:
Raised concentrations of platelet activating factor in colonic mucosa of Crohn's disease patients.
Authors: I Sobhani, S Hochlaf, Y Denizot, C Vissuzaine, E Rene, J Benveniste, M M Lewin, M Mignon
Journal: Gut (1992)

Platelet activating factor (PAF-ACETHER or PAF) and precursors of platelet activating factor were investigated in 26 patients with acute Crohn's disease and in 10 healthy controls. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine, were determined in colonic mucosal biopsies in patients with acute Crohn's disease, during prednisolone therapy, and in remission. Biopsy specimens were submitted to histopathology examination and to phospholipid extraction. Platelet activating factor, lyso platelet activating factor, and alkyl acyl glycerophosphocholine were found in patients with acute Crohn's disease and in remission as well as in controls. Whatever the site of the biopsy, the level of platelet activating factor in colonic mucosa was higher (p < 0.01) in Crohn's disease than in controls. There was no correlation between the level of colonic PAF-ACETHER and age, sex, Crohn's disease activity index, and biological parameters in sera. Although concentrations of colonic platelet activating factor content were higher (p < 0.01) when colonic mucosa displayed cell infiltration, they were neither related to the severity nor the type of inflammatory cells. Platelet activating factor decreases with prednisolone therapy and might return to normal concentrations in quiescent patients. Lyso platelet activating factor and alkyl acyl glycerophosphocholine were not significantly higher in Crohn's disease than in controls. These data suggest that platelet activating factor may be involved in the pathogenesis of Crohn's disease and that it could be used as a marker of the mucosal activity of the disease.
Germline <i>BRCA</i> Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer
Authors: Elena Castro, Chee Goh, David Olmos, Ed Saunders, Daniel Leongamornlert, Malgorzata Tymrakiewicz, Nadiya Mahmud, Tokhir Dadaev, Koveela Govindasami, Michelle Guy, Emma Sawyer, Rosemary Wilkinson, Audrey Ardern-Jones, Steve Ellis, Debra Frost, Susan Peock, D. Gareth Evans, Marc Tischkowitz, Trevor Cole, Rosemarie Davidson, Diana Eccles, Carole Brewer, Fiona Douglas, Mary E. Porteous, Alan Donaldson, Huw Dorkins, Louise Izatt, Jackie Cook, Shirley Hodgson, M. John Kennedy, Lucy E. Side, Jacqueline Eason, Alex Murray, Antonis C. Antoniou, Douglas F. Easton, Zsofia Kote-Jarai, Rosalind Eeles
Journal: Journal of Clinical Oncology (2013)

To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes.
Comparison of hypertonic saline solutions and dextran in dialysis-induced hypotension.
Authors: R Gong, J Lindberg, J Abrams, W R Whitaker, C E Wade, S Gouge
Journal: Journal of the American Society of Nephrology (1993)

The efficacy of three hypertonic saline solutions for treating dialysis-induced hypotension in a randomized, blinded, crossover clinical trial of 10 patients (a minimum of three cycles per solution) was compared. Dialysis-induced hypotension, defined as a decrease in systolic blood pressure of at least 10 mm Hg or systolic blood pressure less than 100 mm Hg, was treated with an iv bolus of either 10 mL of 23% saturated hypertonic saline, 30 mL of 7.5% hypertonic saline, or 30 mL of 7.5% saline with 6% dextran 70, each containing similar osmolar loads of 80, 80, and 100 mosM, respectively. All three solutions raised systolic blood pressure within 5 min (mean pretreatment systolic blood pressure, 87 mm Hg; mean posttreatment systolic blood pressure, 101 mm Hg; P < 0.05). The magnitude of the increase was greater with saturated hypertonic saline (15 mm Hg) and dextran 70 (17 mm Hg) compared with that with hypertonic saline (9 mm Hg; P < 0.05). At 10 min, dialysis-induced hypotension was less frequent with saturated hypertonic saline (incidence, 9%) compared with hypertonic saline (45%). Beyond 10 min, however, there was a trend toward a lower incidence of further dialysis-induced hypotension with dextran 70. There were no side effects. Given equal osmole loads, the more concentrated solution produced a greater increase in systolic blood pressure. The addition of an oncotic agent such as dextran may prolong the blood pressure response beyond 10 min. It was concluded that hypertonic saline solutions safely and effectively treat dialysis-induced hypotension.
Tuberculosis in the Inuit Community of Quebec, Canada
Authors: Dao Nguyen, Jean-François Proulx, Jennifer Westley, Louise Thibert, Serge Dery, Marcel A. Behr
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

In low-incidence countries targeting tuberculosis (TB) elimination, TB remains a problem of a few high-risk groups. In Canada, Aboriginals, and particularly the Arctic Inuit communities, have witnessed dramatic decreases in TB during the 1960s to 1970s, but rates remain at least 10 to 20 times higher than the national average. We are describing the results of an integrated traditional and molecular epidemiology study of all culture-positive Mycobacterium tuberculosis cases in the Arctic Inuit communities of Quebec from 1990 until 2000. The demographic characteristics of the 46 TB cases included in the study were most notable for a bimodal age distribution (48% under 25 years). Genotyping analysis using multiple modalities (IS6110 restriction fragment length polymorphism, spoligotype, mycobacterial interspersed repetitive units-variable number tandem repeats) showed that 76% (35/46) of TB cases were clustered (six clusters, median size four cases) and estimated that at least 62.5% of TB cases were due to ongoing transmission. By integrating the epidemiologic and genotyping data, we observed that the genotyping clustering results were concordant with recognized epidemiologic links but most notably identified previously unrecognized intervillage transmission. This study demonstrates significant ongoing transmission in a geographically isolated, low-density population. In a resource-rich country such as Canada, these communities illustrate some of the persistent challenges of TB control and elimination.
Metabolomics by Proton Nuclear Magnetic Resonance Spectroscopy of the Response to Chloroethylnitrosourea Reveals Drug Efficacy and Tumor Adaptive Metabolic Pathways
Authors: Daniel Morvan, Aicha Demidem
Journal: Cancer Research (2007)

Abstract Metabolomics of tumors may allow discovery of tumor biomarkers and metabolic therapeutic targets. Metabolomics by two-dimensional proton high-resolution magic angle spinning nuclear magnetic resonance spectroscopy was applied to investigate metabolite disorders following treatment by chloroethylnitrosourea of murine B16 melanoma (n = 33) and 3LL pulmonary carcinoma (n = 31) in vivo. Treated tumors of both types resumed growth after a delay. Nitrosoureas provoke DNA damage but the metabolic consequences of genotoxic stress are little known yet. Although some differences were observed in the metabolite profile of untreated tumor types, the prominent metabolic features of the response to nitrosourea were common to both. During the growth inhibition phase, there was an accumulation of glucose (more than ×10; P &amp;lt; 0.05), glutamine (×3 to 4; P &amp;lt; 0.01), and aspartate (×2 to 5; P &amp;lt; 0.01). This response testified to nucleoside de novo synthesis down-regulation and drug efficacy. However, this phase also involved the increase in alanine (P &amp;lt; 0.001 in B16 melanoma), the decrease in succinate (P &amp;lt; 0.001), and the accumulation of serine-derived metabolites (glycine, phosphoethanolamine, and formate; P &amp;lt; 0.01). This response witnessed the activation of pathways implicated in energy production and resumption of nucleotide de novo synthesis, thus metabolic pathways of DNA repair and adaptation to treatment. During the growth recovery phase, it remained polyunsaturated fatty acid accumulation (×1.5 to 2; P &amp;lt; 0.05) and reduced utilization of glucose compared with glutamine (P &amp;lt; 0.05), a metabolic fingerprint of adaptation. Thus, this study provides the proof of principle that metabolomics of tumor response to an anticancer agent may help discover metabolic pathways of drug efficacy and adaptation to treatment. [Cancer Res 2007;67(5):2150–9]
A phase II trial evaluating two schedules of sagopilone (ZK-EPO), a novel epothilone, in patients with platinum-resistant ovarian cancer
Authors: G. Rustin, N. Reed, G.C. Jayson, J.A. Ledermann, M. Adams, T. Perren, C. Poole, M. Lind, M. Persic, S. Essapen, M. Gore, H. Calvert, C. Stredder, A. Wagner, M. Giurescu, S. Kaye
Journal: Annals of Oncology (2011)
Comparative Analysis of Genetically Modified Dendritic Cells and Tumor Cells as Therapeutic Cancer Vaccines
Authors: Christoph Klein, Hansruedi Bueler, Richard C. Mulligan
Journal: The Journal of Experimental Medicine (2000)

We have directly compared the efficacy of two immunotherapeutic strategies for the treatment of cancer: “vaccination” of tumor-bearing mice with genetically modified dendritic cells (DCs), and vaccination with genetically modified tumor cells. Using several different preexisting tumor models that make use of B16F10 melanoma cells expressing a target tumor antigen (human melanoma-associated gene [MAGE]-1), we found that vaccination with bone marrow–derived DCs engineered to express MAGE-1 via adenoviral-mediated gene transfer led to a dramatic decrease in the number of metastases in a lung metastasis model, and led to prolonged survival and some long-term cures in a subcutaneous preexisting tumor model. In contrast, vaccination with granulocyte/macrophage colony-stimulating factor (GM-CSF)–transduced tumor cells, previously shown to induce potent antitumor immunity in standard tumor challenge assays, led to a decreased therapeutic effect in the metastasis model and no effect in the subcutaneous tumor model. Further engineering of DCs to express either GM-CSF, tumor necrosis factor α, or CD40 ligand via retroviral-mediated gene transfer, led to a significantly increased therapeutic effect in the subcutaneous tumor model. The immunological mechanism, as shown for GM-CSF–transduced DCs, involves MAGE-1–specific CD4+ and CD8+ T cells. Expression of GM-CSF by DCs led to enhanced cytotoxic T lymphocyte activity, potentially mediated by increased numbers of DCs in draining lymph nodes. Our results suggest that clinical studies involving the vaccination with genetically modified DCs may be warranted.
Mesenteric lymph nodes at the center of immune anatomy
Authors: Andrew J. Macpherson, Karen Smith
Journal: The Journal of Experimental Medicine (2006)

The surface of the intestinal mucosa is constantly assaulted by food antigens and enormous numbers of commensal microbes and their products, which are sampled by dendritic cells (DCs). Recent work shows that the mesenteric lymph nodes (MLNs) are the key site for tolerance induction to food proteins and that they also act as a firewall to prevent live commensal intestinal bacteria from penetrating the systemic immune system.
Protein Kinase Cε Interacts With and Inhibits the Permeability Transition Pore in Cardiac Mitochondria
Authors: Christopher P. Baines, Chang-Xu Song, Yu-Ting Zheng, Guang-Wu Wang, Jun Zhang, Ou-Li Wang, Yiru Guo, Roberto Bolli, Ernest M. Cardwell, Peipei Ping
Journal: Circulation Research (2003)

Although functional coupling between protein kinase Cε (PKCε) and mitochondria has been implicated in the genesis of cardioprotection, the signal transduction mechanisms that enable this link and the identities of the mitochondrial proteins modulated by PKCε remain unknown. Based on recent evidence that the mitochondrial permeability transition pore may be involved in ischemia/reperfusion injury, we hypothesized that protein-protein interactions between PKCε and mitochondrial pore components may serve as a signaling mechanism to modulate pore function and thus engender cardioprotection. Coimmunoprecipitation and GST-based affinity pull-down from mouse cardiac mitochondria revealed interaction of PKCε with components of the pore, namely voltage-dependent anion channel (VDAC), adenine nucleotide translocase (ANT), and hexokinase II (HKII). VDAC1, ANT1, and HKII were present in the PKCε complex at ≈2%, ≈0.2%, and ≈1% of their total expression, respectively. Moreover, in vitro studies demonstrated that PKCε can directly bind and phosphorylate VDAC1. Incubation of isolated cardiac mitochondria with recombinant PKCε resulted in a significant inhibition of Ca 2+ -induced mitochondrial swelling, an index of pore opening. Furthermore, cardiac-specific expression of active PKCε in mice, which is cardioprotective, greatly increased interaction of PKCε with the pore components and inhibited Ca 2+ -induced pore opening. In contrast, cardiac expression of kinase-inactive PKCε did not affect pore opening. Finally, administration of the pore opener atractyloside significantly attenuated the infarct-sparing effect of PKCε transgenesis. Collectively, these data demonstrate that PKCε forms physical interactions with components of the cardiac mitochondrial pore. This in turn inhibits the pathological function of the pore and contributes to PKCε-induced cardioprotection.
The Oslo definitions for coeliac disease and related terms
Authors: Jonas F Ludvigsson, Daniel A Leffler, Julio C Bai, Federico Biagi, Alessio Fasano, Peter H R Green, Marios Hadjivassiliou, Katri Kaukinen, Ciaran P Kelly, Jonathan N Leonard, Knut Erik Aslaksen Lundin, Joseph A Murray, David S Sanders, Marjorie M Walker, Fabiana Zingone, Carolina Ciacci
Journal: Gut (2012)

<h3>Objective</h3> The literature suggests a lack of consensus on the use of terms related to coeliac disease (CD) and gluten. <h3>Design</h3> A multidisciplinary task force of 16 physicians from seven countries used the electronic database PubMed to review the literature for CD-related terms up to January 2011. Teams of physicians then suggested a definition for each term, followed by feedback of these definitions through a web survey on definitions, discussions during a meeting in Oslo and phone conferences. In addition to ‘CD’, the following descriptors of CD were evaluated (in alphabetical order): asymptomatic, atypical, classical, latent, non-classical, overt, paediatric classical, potential, refractory, silent, subclinical, symptomatic, typical, CD serology, CD autoimmunity, genetically at risk of CD, dermatitis herpetiformis, gluten, gluten ataxia, gluten intolerance, gluten sensitivity and gliadin-specific antibodies. <h3>Results</h3> CD was defined as ‘a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals’. Classical CD was defined as ‘CD presenting with signs and symptoms of malabsorption. Diarrhoea, steatorrhoea, weight loss or growth failure is required.’ ‘Gluten-related disorders’ is the suggested umbrella term for all diseases triggered by gluten and the term gluten intolerance should not to be used. Other definitions are presented in the paper. <h3>Conclusion</h3> This paper presents the Oslo definitions for CD-related terms.
Immunotherapy of Malignancy in Humans
Authors: E. Carmack Holmes
Journal: JAMA (1975)

Many observations support the premise of a close relationship between immunologic competency and the growth of human cancer. Immunotherapy against cancer in animals has been established. Its function appears to be adjunctive to other treatment modalities that first lower tumor burden. These findings are demonstrated in both clinical and laboratory studies of cancer in humans. At the present time, intralesional injections of BCG vaccine in immunocompetent patients with intradermal metastases are most effective. Immunotherapy with topical administration of 2,4 dinitrochlorobenzene is the treatment of choice in selected patients with squamous or basal cell carcinoma.
Prognostic factors for remission in early rheumatoid arthritis: a multiparameter prospective study
Authors: L Gossec
Journal: Annals of the Rheumatic Diseases (2004)

<b>Objective:</b> To determine prognostic factors for remission in early rheumatoid arthritis. <b>Methods:</b> 191 patients with rheumatoid arthritis whose disease duration was less than one year were followed up prospectively for five years. Remission, defined by a disease activity score (DAS) of &lt;1.6, was used as the outcome measure. Baseline clinical, laboratory, genetic, and radiographic data (with radiographic scores determined by Sharp's method, modified by van der Heijde) were obtained. <b>Results:</b> 48 patients (25.1%) fulfilled the remission criteria at the three year follow up visit, and 30 (15.7%) at three and five years. On univariate analysis by Fisher's exact test, remission at three years and persistent remission at five years were closely correlated with baseline DAS values, C reactive protein level, Ritchie score, health assessment questionnaire score, duration of morning stiffness, and to a lesser extent baseline total radiological scores and rheumatoid factor negativity. No significant correlation was found with sex, age, extra-articular manifestations, erythrocyte sedimentation rate, anti-cyclic citrullinated protein antibodies, anti-keratin antibodies, anti-HSP 90, anticalpastatin antibodies, antinuclear antibodies, or HLA-DRB1* genotypes. Logistic regression analysis showed that the baseline independent variables predictive of remission were low DAS, Ritchie score, morning stiffness duration, and total radiographic score. <b>Conclusions:</b> Baseline prognostic factors for remission in early rheumatoid arthritis were mainly clinical markers of disease activity and radiological scores.
Safety and Efficacy of a Totally Subcutaneous Implantable-Cardioverter Defibrillator
Authors: Raul Weiss, Bradley P. Knight, Michael R. Gold, Angel R. Leon, John M. Herre, Margaret Hood, Mayer Rashtian, Mark Kremers, Ian Crozier, Kerry L. Lee, Warren Smith, Martin C. Burke
Journal: Circulation (2013)

Background— The most frequent complications associated with implantable cardioverter-defibrillators (ICDs) involve the transvenous leads. A subcutaneous implantable cardioverter-defibrillator (S-ICD) has been developed as an alternative system. This study evaluated the safety and effectiveness of the S-ICD System (Cameron Health/Boston Scientific) for the treatment of life-threatening ventricular arrhythmias (ventricular tachycardia/ventricular fibrillation). Methods and Results— This prospective, nonrandomized, multicenter trial included adult patients with a standard indication for an ICD, who neither required pacing nor had documented pace-terminable ventricular tachycardia. The primary safety end point was the 180-day S-ICD System complication-free rate compared with a prespecified performance goal of 79%. The primary effectiveness end point was the induced ventricular fibrillation conversion rate compared with a prespecified performance goal of 88%, with success defined as 2 consecutive ventricular fibrillation conversions of 4 attempts. Detection and conversion of spontaneous episodes were also evaluated. Device implantation was attempted in 321 of 330 enrolled patients, and 314 patients underwent successful implantation. The cohort was followed for a mean duration of 11 months. The study population was 74% male with a mean age of 52±16 years and mean left ventricular ejection fraction of 36±16%. A previous transvenous ICD had been implanted in 13%. Both primary end points were met: The 180-day system complication-free rate was 99%, and sensitivity analysis of the acute ventricular fibrillation conversion rate was &gt;90% in the entire cohort. There were 38 discrete spontaneous episodes of ventricular tachycardia/ventricular fibrillation recorded in 21 patients (6.7%), all of which successfully converted. Forty-one patients (13.1%) received an inappropriate shock. Conclusions— The findings support the efficacy and safety of the S-ICD System for the treatment of life-threatening ventricular arrhythmias. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT01064076.
Chemical and immunological features of pleural effusions: comparison between rheumatoid arthritis and other diseases.
Authors: T Pettersson, M Klockars, P E Hellstrom
Journal: Thorax (1982)

The value of determination of pleural fluid glucose, pH, lactic dehydrogenase, IgG, IgA, IgM, C3, C4, anti-IgG antibody, and hydroxyproline in distinguishing between pleural effusions caused by rheumatoid arthritis (RA) and those resulting from other diseases was studied. The series comprised seven patients with RA and 115 patients with other diseases including systemic lupus erythematosus, tuberculosis, malignant disease, empyema, pneumonia, congestive heart failure, and nonspecific pleural effusion. The low glucose concentration, the low pH and the low C4 level in rheumatoid pleural effusion were the most valuable diagnostic findings. The presence of anti-IgG antibody in pleural fluid was not specific for RA. The concentration of hydroxyproline in pleural fluid and the pleural fluid-to-plasma hydroxyproline ratio were significantly higher in RA than in tuberculosis and malignant disease. The results support the view that local metabolic and immunological phenomena as well as a high turnover of collagen occur in the pleural cavity in RA.
Type 1 and Type 2 Diabetes and Incident Hip Fractures in Postmenopausal Women
Authors: Kristin K. Nicodemus, Aaron R. Folsom
Journal: Diabetes Care (2001)

OBJECTIVE—To examine whether postmenopausal women with diabetes experienced a higher incidence of hip fracture than women without diabetes. RESEARCH DESIGN AND METHODS—A prospective cohort of 32,089 postmenopausal women residing in Iowa were surveyed by mail in 1986 and followed for 11 years. Diabetes status and other potential risk factors were assessed by questionnaires at baseline; incidence of hip fracture was ascertained by follow-up questionnaires. RESULTS—A total of 490 hip fractures were reported over 306,900 person-years of follow-up. After adjustment for age, smoking status, estrogen use, BMI, and waist-to-hip ratio, women with type 1 diabetes (n = 47) were 12.25 times (95% CI 5.05–29.73) more likely to report an incident hip fracture than women without diabetes. Women with type 2 diabetes had a 1.70-fold higher risk (1.21–2.38) of incident hip fracture than women without diabetes. Longer duration of type 2 diabetes was associated with higher incidence, as was use of insulin or oral diabetes medications in women with type 2 diabetes. Furthermore, women who were initially free of diabetes but in whom diabetes developed had a relative risk of hip fracture of 1.60 (1.14–2.25) compared with women who never had diabetes. CONCLUSIONS—Postmenopausal women who have diabetes or in whom diabetes develops are at higher risk for hip fracture than nondiabetic postmenopausal women. Strategies to prevent osteoporosis and/or falling may be especially warranted in women with diabetes.