tbuckley/cabot-search huggingface dataset:
The wound-healing effect of a glycoprotein fraction isolated from aloe vera
Authors: S-W. Choi, B-W. Son, Y-S. Son, Y-I. Park, S-K. Lee, M-H. Chung
Journal: British Journal of Dermatology (2001)

Background Aloe vera has been used as a family medicine for promoting wound healing, but it is not known which component of the plant is effective for this purpose. Objectives To isolate and characterize the component effective in wound healing. Methods Chromatography, electrophoresis and spectroscopic methods were used. The cell‐proliferation activity of each component isolated was measured by a [3H]thymidine uptake assay. The cell‐proliferation activity of the effective component was tested on a three‐dimensional raft culture (cell culture technique by which artificial epidermis is made from keratinocytes). The effect of the active component on cell migration and wound healing was observed on a monolayer of human keratinocytes and in hairless mice. Results A glycoprotein fraction was isolated and named G1G1M1DI2. It showed a single band on sodium dodecyl sulphate–polyacrylamide gel electrophoresis, with an apparent molecular weight of about 5·5 kDa. It exhibited significant [3H]thymidine uptake in squamous cell carcinoma cells. The effect of G1G1M1DI2 on cell migration was confirmed by accelerated wound healing on a monolayer of human keratinocytes. When this fraction was tested on a raft culture, it stimulated the formation of epidermal tissue. Furthermore, proliferation markers (epidermal growth factor receptor, fibronectin receptor, fibronectin, keratin 5/14 and keratin 1/10) were markedly expressed at the immunohistochemical level. The glycoprotein fraction enhanced wound healing in hairless mice by day 8 after injury, with significant cell proliferation. Conclusions It is considered that this glycoprotein fraction is involved in the wound‐healing effect of aloe vera via cell proliferation and migration.
Complete Remission With Tyrosine Kinase Inhibitors in Renal Cell Carcinoma
Authors: Laurence Albiges, Stéphane Oudard, Sylvie Negrier, Armelle Caty, Gwenaëlle Gravis, Florence Joly, Brigitte Duclos, Lionel Geoffrois, Frédéric Rolland, Aline Guillot, Brigitte Laguerre, Eric Legouffe, Frédéric Kohser, Pierre-Yves Dietrich, Christine A. Theodore, Bernard Escudier
Journal: Journal of Clinical Oncology (2012)

Purpose Complete remission (CR) is uncommon during treatment for metastatic renal cell carcinoma (mRCC) with tyrosine kinase inhibitors (TKIs), but it may occur in some patients. It remains a matter of debate whether therapy should be continued after CR. Methods A multicenter, retrospective analysis of a series of patients with mRCC who obtained CR during treatment with TKIs (sunitinib or sorafenib), either alone or with local treatment (surgery, radiotherapy, or radiofrequency ablation), was performed. Results CR was identified in 64 patients; 36 patients had received TKI treatment alone and 28 had also received local treatment. Most patients had clear cell histology (60 of 64 patients), and all had undergone previous nephrectomy. The majority of patients were favorable or intermediate risk; however, three patients were poor risk. Most patients developed CR during sunitinib treatment (59 of 64 patients). Among the 36 patients who achieved CR with TKI alone, eight continued TKI treatment after CR, whereas 28 stopped treatment. Seventeen patients who stopped treatment (61%) are still in CR, with a median follow-up of 255 days. Among the 28 patients in CR after TKI plus local treatment, 25 patients stopped treatment, and 12 of these patients (48%) are still in CR, with a median follow-up of 322 days. Conclusion CR can occur after TKI treatment alone or when combined with local treatment. CR was observed at every metastatic site and in every prognostic group.
High Telomerase Activity in Primary Lung Cancers: Association With Increased Cell Proliferation Rates and Advanced Pathologic Stage
Authors: J. Albanell, M. Engelhardt, W. Han, M. A. S. Moore, F. Lonardo, V. Rusch, J. Langenfeld, D. Klimstra, E. Venkatraman, E. Dmitrovsky
Journal: JNCI Journal of the National Cancer Institute (1997)

Background: Telomerase enzyme activity is not detected in most normal cells, a phenomenon believed to be associated with limitations on cellular proliferation. Since this activity is detected in nearly all human tumors, including non-small-cell lung cancers, it has been suggested that telomerase activation may be coupled to acquisition of the malignant phenotype. In this study, we determined whether telomerase activity was associated with tumor pathologic stage, tumor cell proliferation rates, and clinical outcome in a cohort of patients with resected non-small-cell lung cancer for whom long-term follow-up was available. Methods: Primary tumor specimens from 99 patients treated with surgery alone and six patients treated with surgery after chemotherapy were analyzed. Telomerase activity was measured by means of a modified Telomeric Repeat Amplification Protocol (TRAP) assay. Southern blot analysis of terminal restriction fragments was used to evaluate telomere length. Immunohistochemical analysis of Ki-67, a proliferation-associated nuclear antigen, was used to assess tumor cell proliferation. Results: Telomerase activity was detected in 84 of the 99 tumors treated with surgery alone; this activity was not detected in specimens of adjacent, benign lung tissue. Telomerase was detected in only three of six tumors resected after chemotherapy. For the surgery-alone group, statistically significant positive associations were found between the level of telomerase activity and tumor stage, lymph node metastasis, pathologic TNM (tumor-node-metastasis) stage, and Ki-67 immunostaining; a statistically significant inverse association was found between telomerase activity and patient age. No statistically significant differences in telomere length were found in relation to telomerase activity or pathologic stage. Telomerase activity was not found to be associated with clinical outcome in a multivariate Cox proportional hazards analysis adjusted for tumor stage and lymph node status. Conclusions: High telomerase activity is detected frequently in primary non-small-cell lung cancers that exhibit high tumor cell proliferation rates and advanced pathologic stage.
Consensus statement on blocking the effects of interleukin-6 and in particular by interleukin-6 receptor inhibition in rheumatoid arthritis and other inflammatory conditions
Authors: Josef S Smolen, Monika M Schoels, Norihiro Nishimoto, Ferdinand C Breedveld, Gerd R Burmester, Maxime Dougados, Paul Emery, Gianfranco Ferraccioli, Cem Gabay, Allan Gibofsky, Juan Jesus Gomez-Reino, Graeme Jones, Tore K Kvien, Miho Murakami, Neil Betteridge, Clifton O Bingham, Vivian Bykerk, Ernest H Choy, Bernard Combe, Maurizio Cutolo, Winfried Graninger, Angel Lanas, Emilio Martin-Mola, Carlomaurizio Montecucco, Mikkel Ostergaard, Karel Pavelka, Andrea Rubbert-Roth, Naveed Sattar, Marieke Scholte-Voshaar, Yoshiya Tanaka, Michael Trauner, Gabriele Valentini, Kevin L Winthrop, Maarten de Wit, Désirée van der Heijde
Journal: Annals of the Rheumatic Diseases (2012)

Since approval of tocilizumab (TCZ) for treatment of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA), interleukin 6 (IL-6) pathway inhibition was evaluated in trials of TCZ and other agents targeting the IL-6 receptor and ligand in various RA populations and other inflammatory diseases. This consensus document informs on interference with the IL-6 pathway based on evidence and expert opinion.Preparation of this document involved international experts in RA treatment and RA patients. A systematic literature search was performed that focused on TCZ and other IL6-pathway inhibitors in RA and other diseases. Subsequently, incorporating available published evidence and expert opinion, the steering committee and a broader expert committee (both including RA patients) formulated the current consensus statement.The consensus statement covers use of TCZ as combination- or monotherapy in various RA populations and includes clinical, functional and structural aspects. The statement also addresses the second approved indication in Europe JIA and non-approved indications. Also early phase trials involving additional agents that target the IL-6 receptor or IL-6 were evaluated. Safety concerns, including haematological, hepatic and metabolic issues as well as infections, are addressed likewise.The consensus statement identifies points to consider when using TCZ, regarding indications, contraindications, screening, dose, comedication, response evaluation and safety. The document is aimed at supporting clinicians and informing patients, administrators and payers on opportunities and limitations of IL-6 pathway inhibition.
Preferring Rules to Similarity: Coherence, goals, and commitment
Authors: Emmanuel M. Pothos
Journal: Behavioral and Brain Sciences (2005)

This response to the open peer commentary discusses what should be the appropriate explanatory scope of a rules versus similarity proposal and accordingly evaluates the Rules versus Similarity one. Additionally, coherence, goals, and commitment are presented as inferential notions, fully consistent with the Rules versus Similarity distinction, that allow us to predict when Rules would be preferred to Similarity.
HMGB1-mediated autophagy promotes docetaxel resistance in human lung adenocarcinoma
Authors: Banzhou Pan, Dongqin Chen, Jiayuan Huang, Rui Wang, Bing Feng, Haizhu Song, Longbang Chen
Journal: Molecular Cancer (2014)

Docetaxel resistance remains a major obstacle in the treatment of non-small cell lung cancer (NSCLC). High-mobility group box 1 (HMGB1) has been shown to promote autophagy protection in response to antitumor therapy, but the exact molecular mechanism underlying HMGB1-mediated autophagy has not been clearly defined. Lung adenocarcinoma (LAD) cells were transfected with pcDNA3.1-HMGB1 or HMGB1 shRNA, followed by docetaxel treatment. Cell viability and proliferation were tested by MTT assay and colony formation assay, respectively. Annexin V flow cytometric analysis and western blot analysis of activated caspase3 and cleaved PARP were used to evaluate apoptosis, while immunofluorescence microscopy and transmission electron microscopy were applied to assess autophagy activity. The formation of the Beclin-1-PI3K-III complex was examined by immunoprecipitation analysis. NOD/SCID mice were inoculated with docetaxel-resistant SPC-A1/DTX cells transfected with control or HMGB1 shRNA. HMGB1 translocated from the nucleus to the cytoplasm in LAD cells exposed to docetaxel and acted as a positive regulator of autophagy, which inhibited apoptosis and increased drug resistance. Suppression of HMGB1 restored the sensitivity of LAD cells to docetaxel both in vivo and in vitro. Mechanistic investigation revealed that HMGB1 promoted the formation of the Beclin-1-PI3K-III complex through activating the mitogen-activated protein kinase (MEK)-extracellular signal-regulated kinase (ERK) signaling pathway, thereby regulating autophagosome formation. Our results demonstrated that HMGB1-regulated autophagy is a significant contributor to docetaxel resistance in LAD cells. Suppression of HMGB1 or limiting HMGB1 cytosolic translocation diminished autophagic protection in response to docetaxel in LAD cells.
Comorbidity and Disease Status–Based Risk Stratification of Outcomes Among Patients With Acute Myeloid Leukemia or Myelodysplasia Receiving Allogeneic Hematopoietic Cell Transplantation
Authors: Mohamed L. Sorror, Brenda M. Sandmaier, Barry E. Storer, Michael B. Maris, Frédéric Baron, David G. Maloney, Bart L. Scott, H. Joachim Deeg, Frederick R. Appelbaum, Rainer Storb
Journal: Journal of Clinical Oncology (2007)

Purpose Retrospective studies have shown similar survival among patients with acute myeloid leukemia (AML) and myelodysplasia (MDS) after nonmyeloablative compared with myeloablative conditioning. Refined risk stratification is required to design prospective trials. Patients and Methods We stratified outcomes among patients with AML (n = 391) or MDS (n = 186) who received either nonmyeloablative (n = 125) or myeloablative (n = 452) allogeneic hematopoietic cell transplantation (HCT) based on comorbidities, as assessed by a HCT-specific comorbidity index (HCT-CI), as well as disease status. Patients receiving nonmyeloablative conditioning were older, more frequently pretreated, more often received unrelated grafts, and more often had HCT-CI scores of ≥ 3 compared with patients who received myeloablative conditioning. Results Patients with HCT-CI scores of 0 to 2 and either low or high disease risks had probabilities of overall survival at 2 years of 70% and 57% after nonmyeloablative conditioning compared with 78% and 50% after myeloablative conditioning, respectively. Patients with HCT-CI scores of ≥ 3 and either low or high disease risks had probabilities of overall survival of 41% and 29% with nonmyeloablative conditioning compared with 45% and 24% with myeloablative regimens, respectively. After adjusting for pretransplantation differences, stratified outcomes were not significantly different among patients receiving nonmyeloablative compared with myeloablative conditioning, with the exception of lessened nonrelapse mortality (hazard ratio, 0.50; P = .05) in the highest risk group. Conclusion Patients with low comorbidity scores could be candidates for prospective randomized trials comparing nonmyeloablative and myeloablative conditioning regardless of disease status. Additional data are required for patients with low-risk diseases and high comorbidity scores. Novel antitumor agents combined with nonmyeloablative HCT should be explored among patients with high comorbidity scores and advanced disease.
Association between fish consumption, long chain omega 3 fatty acids, and risk of cerebrovascular disease: systematic review and meta-analysis
Authors: R. Chowdhury, S. Stevens, D. Gorman, A. Pan, S. Warnakula, S. Chowdhury, H. Ward, L. Johnson, F. Crowe, F. B. Hu, O. H. Franco
Journal: BMJ (2012)

<b>Objective</b> To clarify associations of fish consumption and long chain omega 3 fatty acids with risk of cerebrovascular disease for primary and secondary prevention. <b>Design</b> Systematic review and meta-analysis. <b>Data sources</b> Studies published before September 2012 identified through electronic searches using Medline, Embase, BIOSIS, and Science Citation Index databases. <b>Eligibility criteria</b> Prospective cohort studies and randomised controlled trials reporting on associations of fish consumption and long chain omega 3 fatty acids (based on dietary self report), omega 3 fatty acids biomarkers, or supplementations with cerebrovascular disease (defined as any fatal or non-fatal ischaemic stroke, haemorrhagic stroke, cerebrovascular accident, or transient ischaemic attack). Both primary and secondary prevention studies (comprising participants with or without cardiovascular disease at baseline) were eligible. <b>Results</b> 26 prospective cohort studies and 12 randomised controlled trials with aggregate data on 794 000 non-overlapping people and 34 817 cerebrovascular outcomes were included. In cohort studies comparing categories of fish intake the pooled relative risk for cerebrovascular disease for 2-4 servings a week versus ≤1 servings a week was 0.94 (95% confidence intervals 0.90 to 0.98) and for ≥5 servings a week versus 1 serving a week was 0.88 (0.81 to 0.96). The relative risk for cerebrovascular disease comparing the top thirds of baseline long chain omega 3 fatty acids with the bottom thirds for circulating biomarkers was 1.04 (0.90 to 1.20) and for dietary exposures was 0.90 (0.80 to 1.01). In the randomised controlled trials the relative risk for cerebrovascular disease in the long chain omega 3 supplement compared with the control group in primary prevention trials was 0.98 (0.89 to 1.08) and in secondary prevention trials was 1.17 (0.99 to 1.38). For fish or omega 3 fatty acids the estimates for ischaemic and haemorrhagic cerebrovascular events were broadly similar. Evidence was lacking of heterogeneity and publication bias across studies or within subgroups. <b>Conclusions</b> Available observational data indicate moderate, inverse associations of fish consumption and long chain omega 3 fatty acids with cerebrovascular risk. Long chain omega 3 fatty acids measured as circulating biomarkers in observational studies or supplements in primary and secondary prevention trials were not associated with cerebrovascular disease. The beneficial effect of fish intake on cerebrovascular risk is likely to be mediated through the interplay of a wide range of nutrients abundant in fish.
Knowledge and attitudes about tuberculosis among non-medical students in University of Novi Sad, Serbia
Authors: Miroslav Ilic, Miroslav Tomic, Vesna Kuruc, Slobodan Pavlovic, Svetlana Kasikovic-Lecic, Ivan Kopitovic, Senka Milutinov
Journal: European Respiratory Journal (2011)

Introduction:  Students9 knowledge and opinion about tuberculosis (TB) are very important for recognizing early symptoms and signs of disease, prevention of late in diagnosis of TB and influence on prevention and outcome of disease.   Goal:  To define the non-medical students9 knowledge about TB (symptoms, way of medical treatment, possible complications, comorbidity).   Material and methods:  Prospective study comprised the non-medical faculties at the University of Novi Sad, Serbia. The data were obtained by the questionnaire filled in during October-November 2010.   Results:  The total of 1139 students were questioned, average 19,7 year, most women (n=794, 69.7%). The majority of students had a good knowledge about TB (n= 891, 78.2%). The majority of questioned students knew that TB is infectious disease (n=1093, 96%) that the main cause of TB is bacteria (n=887, 77.9%) as well as it is curable disease (n=1079, 95.6%). Over 94% knew that cough is the main cause of TB transmission. 62% questioned students considered that risk factors can contribute the tuberculosis appearance (39.4% alcoholism, 66.3% poor nutrition, 74,7% smoking and 67.9% comorbidities). The students from Agricultural faculty showed better knowledge against other students, p   Conclusion:  Students of non-medical faculties at the University of Novi Sad showed the good knowledge about TB. The best knowledge was noticed at the students of Faculty of Agriculture. They also are well informed about TB presence in the state and the effects of national and international guidelines implementation in the country respectively.
Epicardial Excitation Studies in Dogs with Congenital Right Ventricular Hypertrophy
Authors: JOHN D. HILL, E. NEIL MOORE
Journal: Circulation Research (1967)

The time and sequence of epicardial activation was determined by measuring the onset of activation at 26 to 47 representative epicardial sites on each ventricle. Normal dogs and dogs with right ventricular hypertrophy resulting from various congenital heart lesions were studied. The total right ventricular epicardial activation time was slightly prolonged (10 msec) in some dogs with right ventricular hypertrophy, but it was not directly related to the severity of the lesion. In the dogs with right ventricular hypertrophy and right ventriclepulmonary artery systolic pressure differences greater than 40 mm Hg, the activation of the right ventricular epicardium was consistently completed after that of the left ventricular epicardium. The delay in right ventricular epicardial activation was best shown by plotting the epicardial data on a simultaneously recorded QRS complex. In the dogs with right ventricular hypertrophy, right ventricular epicardial activation was shifted in time within the QRS complex so that 39% of the sites were activated during the last one-third of the QRS interval; only 1% of the right ventricular epicardial sites were activated during this time in the normal group. The QRS electrocardiographic changes in right ventricular hypertrophy were associated not only with a slight prolongation in epicardial activation time, but also with a shift in timing of this activation within the QRS complex.
Effects of CETP and APOE polymorphisms on lipoprotein levels in patients with obstructive sleep apnea
Authors: Radovan Tisko, Zuzana Sopkova, Viera Habalova, Zuzana Dorkova, Eva Slaba, Martin Javorsky, Ivan Tkac, Ruzena Tkacova
Journal: European Respiratory Journal (2012)

Rationale. Cholesterol ester transfer protein (CETP) and apoliprotein E (APOE) polymorphisms were related to serum lipids in association studies. In a mouse model of obstructive sleep apnea (OSA) hypoxia inhibited clearance of triglyceride-rich lipoproteins. Since hypoxia might interfere with genetic background to affect lipid levels, we examined effects of interactions between CETP and APOE variants and hypoxia on serum lipids in OSA patients.

Methods. 634 adult subjects evaluated for suspected OSA underwent overnight polysomnography. The association of HDL-cholesterol (HDLC), triglycerides (TG) and LDL-cholesterol (LDLC) with OSA-related hypoxia reflected by oxygen desaturation index (ODI) was examined and adjusted for relevant covariates.

Findings. Patients were 69.1% male (age 51.1±11.2 years, apnoea-hypopnoea index 30.4±29.9). In univariate analyses, HDLC was related to the both ODI and CETP polymorphism (R=-0.196, p<0.001; R=0.123, p=0.002). In multivariate analysis only CETP genotype remained associated with HDLC (R2=0.185, p=0.002) and no interaction between CETP variant and ODI was observed. In contrast, TG were related to ODI and APOE polymorphism in the univariate analyses (R=0.284, p<0.001; R=0.100, p=0.013), and also after adjustments (R2=0.382, p=0.046, p=0.002). Significant interaction between APOE genotype and ODI was observed with respect to TG levels (p=0.010 for the interaction term APOE*ODI).

Conclusion. Our findings support the role of CETP and APOE polymorphisms in atherogenic dyslipidaemia in OSA patients, and suggest the presence of an interaction between hypoxia and APOE genotype to affect TG levels.

Funding. APVV-0134-11, VEGA 1/0111/12, Slovakia.
Low-level Hypermutation in T Cell–independent Germinal Centers Compared with High Mutation Rates Associated with T Cell–dependent Germinal Centers
Authors: Kai-Michael Toellner, William E. Jenkinson, Dale R. Taylor, Mahmood Khan, Daniel M.-Y. Sze, David M. Sansom, Carola G. Vinuesa, Ian C.M. MacLennan
Journal: The Journal of Experimental Medicine (2002)

Exceptionally germinal center formation can be induced without T cell help by polysaccharide-based antigens, but these germinal centers involute by massive B cell apoptosis at the time centrocyte selection starts. This study investigates whether B cells in germinal centers induced by the T cell–independent antigen (4-hydroxy-3-nitrophenyl)acetyl (NP) conjugated to Ficoll undergo hypermutation in their immunoglobulin V region genes. Positive controls are provided by comparing germinal centers at the same stage of development in carrier-primed mice immunized with a T cell–dependent antigen: NP protein conjugate. False positive results from background germinal centers and false negatives from non-B cells in germinal centers were avoided by transferring B cells with a transgenic B cell receptor into congenic controls not carrying the transgene. By 4 d after immunization, hypermutation was well advanced in the T cell–dependent germinal centers. By contrast, the mutation rate for T cell–independent germinal centers was low, but significantly higher than in NP-specific B cells from nonimmunized transgenic mice. Interestingly, a similar rate of mutation was seen in extrafollicular plasma cells at this stage. It is concluded that efficient activation of hypermutation depends on interaction with T cells, but some hypermutation may be induced without such signals, even outside germinal centers.