tbuckley/cabot-search huggingface dataset:
Gene Transfer of the Urokinase-Type Plasminogen Activator Receptor-Targeted Matrix Metalloproteinase Inhibitor TIMP-1.ATF Suppresses Neointima Formation More Efficiently Than Tissue Inhibitor of Metalloproteinase-1
Authors: M.L.M. Lamfers, J.M. Grimbergen, M.C. Aalders, M.J. Havenga, M.R. de Vries, L.G.M. Huisman, V.W.M. van Hinsbergh, P.H.A. Quax
Journal: Circulation Research (2002)

Proteases of the plasminogen activator (PA) and matrix metalloproteinase (MMP) system play an important role in smooth muscle cell (SMC) migration and neointima formation after vascular injury. Inhibition of either PAs or MMPs has previously been shown to result in decreased neointima formation in vivo. To inhibit both protease systems simultaneously, a novel hybrid protein, TIMP-1.ATF, was constructed consisting of the tissue inhibitor of metalloproteinase-1 (TIMP-1) domain, as MMP inhibitor, linked to the receptor-binding amino terminal fragment (ATF) of urokinase. By binding to the u-PA receptor this protein will not only anchor the TIMP-1 moiety directly to the cell surface, it will also prevent the local activation of plasminogen by blocking the binding of urokinase-type plasminogen activator (u-PA) to its receptor. Adenoviral expression of TIMP-1.ATF was used to inhibit SMC migration and neointima formation in human saphenous vein segments in vitro. SMC migration was inhibited by 65% in Ad.TIMP-1.ATF-infected cells. Infection with adenoviral vectors encoding the individual domains, Ad.TIMP-1 and Ad.ATF, reduced migration by 32% and 52%, respectively. Neointima formation in saphenous vein organ cultures infected with Ad.TIMP-1.ATF was inhibited by 72% compared with 42% reduction after Ad.TIMP-1 infection and 34% after Ad.ATF infection. These data show that binding of TIMP-1.ATF hybrid protein to the u-PA receptor at the cell surface strongly enhances the inhibitory effect of TIMP-1 on neointima formation in human saphenous vein cultures.
Transcriptomic Signatures Mirror the Lack of the Fecundity/Longevity Trade-Off in Ant Queens
Authors: Katharina von Wyschetzki, Olav Rueppell, Jan Oettler, Jürgen Heinze
Journal: Molecular Biology and Evolution (2015)

Life-history theory predicts a trade-off between reproductive investment and self-maintenance. The negative association between fertility and longevity found throughout multicellular organisms supports this prediction. As an important exception, the reproductives of many eusocial insects (ants, bees, and termites) are simultaneously very long-lived and highly fertile. Here, we examine the proximate basis for this exceptional relationship by comparing whole-body transcriptomes of differently aged queens of the ant Cardiocondyla obscurior. We show that the sets of genes differentially expressed with age significantly overlap with age-related expression changes previously found in female Drosophila melanogaster. We identified several developmental processes, such as the generation of neurons, as common signatures of aging. More generally, however, gene expression in ant queens and flies changes with age mainly in opposite directions. In contrast to flies, reproduction-associated genes were upregulated and genes associated with metabolic processes and muscle contraction were downregulated in old relative to young ant queens. Furthermore, we searched for putative C. obscurior longevity candidates associated with the previously reported lifespan-prolonging effect of mating by comparing the transcriptomes of queens that differed in mating and reproductive status. We found 21 genes, including the putative aging candidate NLaz (an insect homolog of APOD), which were consistently more highly expressed in short-lived, unmated queens than in long-lived, mated queens. Our study provides clear evidence that the alternative regulation of conserved molecular pathways that mediate the interplay among mating, egg laying, and aging underlies the lack of the fecundity/longevity trade-off in ant queens.
Ulcers and Gastritis
Authors: G. N. J. Tytgat
Journal: Endoscopy (1998)

Once again this year, developments in the field of ulcers and gastritis have been entirely dominated by findings relating to Helicobacter pylori. However, interest in H. pylori can be expected to decline, since the prevalence of the infection is rapidly decreasing in the developing world - to the point that many gastroduodenal ulcers are now unrelated to H. pylori A further reason for declining interest is disappointment regarding the role of H. pylori in dyspepsia. The expected reduction in the endoscopic workload produced by screening for H. pylori or cagA positivity has so far not occurred. The exact role of the damage caused by nonsteroidal anti-inflammatory drugs in H. pylori-infected stomachs remains controversial. Equally controversial is the magnitude of the increased reflux symptomatology and reflux disease observed after H. pylori infection has been cured in patients with ulcer disease. Eradication therapy is largely dominated by proton-pump inhibitor triple therapies, although the efficacy of these is declining. Bismuth triple therapy and quadruple therapy continue to be valid alternatives.
Antigen- and receptor-driven regulatory mechanisms. IV. Idiotype-bearing I-J+ suppressor T cell factors induce second-order suppressor T cells which express anti-idiotypic receptors.
Authors: M S Sy, M H Dietz, R N Germain, B Benacerraf, M I Greene
Journal: The Journal of Experimental Medicine (1980)

Administration of azobenzenearsonate (ABA)-coupled syngeneic spleen cells intravenously to A/J mice leads to the generation of suppressor T cells (Ts1) which exhibit specific binding to ABA-bovine serum albumin (BSA)-coated dishes. These Ts1 share idiotypic determinants with the major cross-reactive idiotype (CRI) of the anti-ABA antibodies of A/J mice, and also produce a soluble suppressor factor (TsF) bearing CRI and I-J subregion-coded determinants. Injection of this TsF into naive A/J mice elicits a second set of specific suppressor cells (Ts2) which are not lysed by anti-CRI antibody plus C, and which do not bind to ABA-BSA-coated dishes. However, in contrast with Ts1, these Ts2 do bind to plates bearing CRI+ anti-ABA immunoglobulin. Thus, Ts2 exhibit anti-idiotypic specificity. These data indicate that antigen elicits the production of a soluble T cell product bearing both variable portion of the Ig heavy chain (VH) and I-J subregion-coded determinants which serves to communicate between T cell subsets to establish an idiotype-anti-idiotype regulatory pathway.
Genes Upregulated in Prostate Cancer Reactive Stroma Promote Prostate Cancer Progression <i>In Vivo</i>
Authors: Olga Dakhova, David Rowley, Michael Ittmann
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Marked reactive stroma formation is associated with poor outcome in clinically localized prostate cancer. We have previously identified genes with diverse functions that are upregulated in reactive stroma. This study tests the hypothesis that expression of these genes in stromal cells enhances prostate cancer growth in vivo. Experimental Design: The expression of reactive stroma genes in prostate stromal cell lines was evaluated by reverse transcriptase (RT)-PCR and qRT-PCR. Genes were knocked down using stable expression of short-hairpin RNAs (shRNA) and the impact on tumorigenesis assessed using the differential reactive stroma (DRS) system, in which prostate stromal cell lines are mixed with LNCaP prostate cancer cells and growth as subcutaneous xenografts assessed. Results: Nine of 10 reactive stroma genes tested were expressed in one or more prostate stromal cell lines. Gene knockdown of c-Kit, Wnt10B, Bmi1, Gli2, or COMP all resulted in decreased tumorigenesis in the DRS model. In all tumors analyzed, angiogenesis was decreased and there were variable effects on proliferation and apoptosis in the LNCaP cells. Wnt10B has been associated with stem/progenitor cell phenotype in other tissue types. Using a RT-PCR array, we detected downregulation of multiple genes involved in stem/progenitor cell biology such as OCT4 and LIF as well as cytokines such as VEGFA, BDNF, and CSF2 in cells with Wnt10B knockdown. Conclusions: These findings show that genes upregulated in prostate cancer–reactive stroma promote progression when expressed in prostate stromal cells. Moreover, these data indicate that the DRS model recapitulates key aspects of cancer cell/reactive stroma interactions in prostate cancer. Clin Cancer Res; 20(1); 100–9. ©2013 AACR.
Linking genes to literature: text mining, information extraction, and retrieval applications for biology
Authors: Martin Krallinger, Alfonso Valencia, Lynette Hirschman
Journal: Genome biology (2008)

Efficient access to information contained in online scientific literature collections is essential for life science research, playing a crucial role from the initial stage of experiment planning to the final interpretation and communication of the results. The biological literature also constitutes the main information source for manual literature curation used by expert-curated databases. Following the increasing popularity of web-based applications for analyzing biological data, new text-mining and information extraction strategies are being implemented. These systems exploit existing regularities in natural language to extract biologically relevant information from electronic texts automatically. The aim of the BioCreative challenge is to promote the development of such tools and to provide insight into their performance. This review presents a general introduction to the main characteristics and applications of currently available text-mining systems for life sciences in terms of the following: the type of biological information demands being addressed; the level of information granularity of both user queries and results; and the features and methods commonly exploited by these applications. The current trend in biomedical text mining points toward an increasing diversification in terms of application types and techniques, together with integration of domain-specific resources such as ontologies. Additional descriptions of some of the systems discussed here are available on the internet http://zope.bioinfo.cnio.es/bionlp_tools/ .
The Developmentally Regulated Expression of <i>Twisted Gastrulation</i> Reveals a Role for Bone Morphogenetic Proteins in the Control of T Cell Development
Authors: Daniel Graf, Suran Nethisinghe, Donald B. Palmer, Amanda G. Fisher, Matthias Merkenschlager
Journal: The Journal of Experimental Medicine (2002)

The evolutionarily conserved, secreted protein Twisted gastrulation (Tsg) modulates morphogenetic effects of decapentaplegic (dpp) and its orthologs, the bone morphogenetic proteins 2 and 4 (BMP2/4), in early Drosophila and vertebrate embryos. We have uncovered a role for Tsg at a much later stage of mammalian development, during T cell differentiation in the thymus. BMP4 is expressed by thymic stroma and inhibits the proliferation of CD4−CD8− double-negative (DN) thymocytes and their differentiation to the CD4+CD8+ double-positive (DP) stage in vitro. Tsg is expressed by thymocytes and up-regulated after T cell receptor signaling at two developmental checkpoints, the transition from the DN to the DP and from the DP to the CD4+ or CD8+ single-positive stage. Tsg can synergize with the BMP inhibitor chordin to block the BMP4-mediated inhibition of thymocyte proliferation and differentiation. These data suggest that the developmentally regulated expression of Tsg may allow thymocytes to temporarily withdraw from inhibitory BMP signals.
Community-based evaluation of immigrant tuberculosis screening using interferon γ release assays and tuberculin skin testing: observational study and economic analysis
Authors: Manish Pareek, Marion Bond, Jennifer Shorey, Suranjith Seneviratne, Margaret Guy, Peter White, Ajit Lalvani, Onn Min Kon
Journal: Thorax (2012)

<h3>Background</h3> UK tuberculosis (TB) notifications are rising due to disease in the immigrant population. National screening guidelines have been revised but cost-effectiveness analyses are hampered by the lack of data on the comparative performance of tuberculin skin tests (TSTs) and interferon γ release assays (IGRAs) in immigrants. <h3>Methods</h3> Three-way evaluation of TSTs and two IGRAs (QuantiFERON Gold in-tube (QFN-GIT) and T-SPOT.TB) in immigrants aged ≥16 years to quantify test positivity, concordance and factors associated with positivity. Yields were computed at different incidence thresholds and the relative cost-effectiveness of screening was estimated using different latent TB infection (LTBI) screening modalities at varying incidence thresholds with or without port-of-arrival chest x-ray (CXR). <h3>Results</h3> 231 immigrants were included; median age 29 (IQR 24–37). TSTs were accepted by 80.9%, read in 93.5% and 30.3% were positive – QFN-GIT and T-SPOT.TB positive in 16.6% and 22.5% respectively. Positive TSTs, QFN-GIT and T-SPOT.TB were independently associated with increasing TB incidence in immigrants9 countries of origin (p=0.007, 0.007, 0.037 respectively). Implementing current guidance (threshold 40/100 000 per year) would identify 98–100% of LTBIs (depending on test) but entail testing 97–99% of the cohort; screening at 150/100 000 per year would identify 49–71% of LTBIs but only entail screening half the cohort. The two most cost-effective screening strategies were no port-of-entry chest radiography and screen with single-step QFN-GIT at 250/100 000 per year (incremental cost-effectiveness ratio (ICER)) £21 565.3/case averted); and no port-of-entry CXR and screen with single-step QFN-GIT at 150/100 000 per year (averted additional 7.8 TB cases; ICER £31 867.1/case averted). <h3>Conclusions</h3> UK immigrant screening could cost-effectively and safely eliminate mandatory CXR on arrival by emphasising systematic screening for LTBI with single-step IGRA. Intermediate incidence thresholds balance the need to identify as many imported LTBIs as possible against limited service capacity.
Transbronchial versus Transesophageal Ultrasound-guided Aspiration of Enlarged Mediastinal Lymph Nodes
Authors: Felix J. F. Herth, William Lunn, Ralf Eberhardt, Heinrich D. Becker, Armin Ernst
Journal: American Journal of Respiratory and Critical Care Medicine (2005)

Rationale: Transesophageal and transbronchial, ultrasound-guided, fine-needle aspiration of enlarged mediastinal lymph nodes have become popular, but have never been compared directly. Objectives: To compare the relative diagnostic yield and ability of the transesophageal and transbronchial approaches to reach abnormal mediastinal lymph nodes. Methods: A total of 160 patients with enlarged lymph nodes in one of eight mediastinal lymph node stations underwent transbronchial and transesophageal biopsies in a crossover design. Each of the eight stations was allocated 20 patients. Two needle punctures were done with each approach. Measurements: Percentage of successful biopsies, percentage of patients diagnosed, and biopsy time were measured from when the lymph node was identified with ultrasound. Main Results: Among the 106 men and 54 women (mean age 53.2 years), transbronchial aspiration was successful in 85%, and transesophageal aspiration was successful in 78% (p = 0.2). For each station, the number of positive samples for the transbronchial/transesophageal approaches was: 2R: 19/13; 2L: 16/19; 3: 17/15; 4R: 19/12; 4L: 17/20; 7: 19/20; 10R: 18/9; and 10L: 17/18. Combining both approaches produced successful biopsies in 97% and diagnoses in 94% of patients. Mean biopsy times were 3.2 minutes for the transbronchial approach and 4.1 minutes for the transesophageal approach. The transbronchial approach was superior in nodes 2R, 4R, and 10R. No complications were encountered. Conclusions: In experienced hands, enlarged mediastinal lymph nodes may be aspirated with either the transbronchial or transesophageal approach. These nonsurgical approaches have similar diagnostic yields, although the transbronchial approach is superior for right-sided lymph nodes. Combining both approaches provides results similar those of mediastinoscopy.
Interrupted coding sequences in Mycobacterium smegmatis: authentic mutations or sequencing errors?
Authors: Caroline Deshayes, Emmanuel Perrodou, Sebastien Gallien, Daniel Euphrasie, Christine Schaeffer, Alain Van-Dorsselaer, Olivier Poch, Odile Lecompte, Jean-Marc Reyrat
Journal: Genome biology (2007)

Abstract Background In silico analysis has shown that all bacterial genomes contain a low percentage of ORFs with undetected frameshifts and in-frame stop codons. These interrupted coding sequences (ICDSs) may really be present in the organism or may result from misannotation based on sequencing errors. The reality or otherwise of these sequences has major implications for all subsequent functional characterization steps, including module prediction, comparative genomics and high-throughput proteomic projects. Results We show here, using Mycobacterium smegmatis as a model species, that a significant proportion of these ICDSs result from sequencing errors. We used a resequencing procedure and mass spectrometry analysis to determine the nature of a number of ICDSs in this organism. We found that 28 of the 73 ICDSs investigated correspond to sequencing errors. Conclusion The correction of these errors results in modification of the predicted amino acid sequences of the corresponding proteins and changes in annotation. We suggest that each bacterial ICDS should be investigated individually, to determine its true status and to ensure that the genome sequence is appropriate for comparative genomics analyses.
Response of the skin in dermatitis herpetiformis to a gluten free diet, with reference to jejunal morphology.
Authors: B T Cooper, E Mallas, M D Trotter, W T Cooke
Journal: Gut (1978)

Twenty-one patients with dermatitis herpetiformis have been on a gluten free diet regularly followed up for at least one year (mean four years). Eighteen patients had a 9flat9 mucosal appearance (grade III), one patient had moderately severe mucosal abnormality (grade II), one patient had mild mucosal abnormality (grade I), and one patient had a normal mucosal appearance (grade O). On the diet, 10 patients had no skin rash and took no dapsone, seven patients controlled the skin rash on a lower dose of dapsone, and four noticed no improvement. There was no correlation between pre-diet jejunal morphology and response of the skin. A repeat jejunal biopsy, on the gluten free diet, was possible in 15 patients. While all those with skin improvement showed some improvement in jejunal morphology, there was no association between the degree of skin improvement and the degree of recovery of the jejunal mucosa.
18F-FDG-PET/CT Imaging as an Early Survival Predictor in Patients with Primary High-Grade Soft Tissue Sarcomas Undergoing Neoadjuvant Therapy
Authors: Ken Herrmann, Matthias R. Benz, Johannes Czernin, Martin S. Allen-Auerbach, William D. Tap, Sarah M. Dry, Tibor Schuster, Jeff J. Eckardt, Michael E. Phelps, Wolfgang A. Weber, Fritz C. Eilber
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Neoadjuvant therapy is associated with considerable toxicity and limited survival benefits in patients with soft tissue sarcoma (STS). We prospectively evaluated whether 2[18F]fluoro-2-deoxy-d-glucose (18F-FDG)-PET/computed tomographic (CT) imaging after the initial cycle of neoadjuvant therapy could predict overall survival in these patients. Experimental Design: Thirty-nine patients underwent 18F-FDG-PET/CT before and after one cycle of neoadjuvant therapy. Fifty-six patients underwent end-of-treatment PET. Overall survival was, among others, correlated with changes of SUVpeak and histopathology. Results: One-, two-, and five-year survival rates were 95% ± 3.0%, 86% ± 4.6%, and 68% ± 6.6%, respectively. Median time to death was 30.9 months (mean, 27.7; range, 6.9–50.1). Optimal cutoff values for early and late decreases in SUVpeak (26% and 57%, respectively) were significant predictors of survival in univariate survival analysis [P = 0.041; HR, 0.27; 95% confidence interval (CI), 0.08–0.95 and P = 0.045; HR, 0.31; 95% CI, 0.10–0.98]. Seven of 15 early PET nonresponders but only four of 24 early PET responders died during follow-up (P = 0.068). The only other significant survival predictor was surgical margin positivity (P = 0.041; HR, 3.31; 95% CI, 1.05–10.42). By multivariable analysis, early metabolic response (P = 0.016) and positivity of surgical margins (P = 0.036) remained significant survival predictors. Conclusion: 18F-FDG-PET predicted survival after the initial cycle of neoadjuvant chemotherapy in patients with STS and can potentially serve as an intermediate endpoint biomarker in clinical research and patient care. Clin Cancer Res; 18(7); 2024–31. ©2012 AACR.
Nephrogenic fibrosing dermopathy: response to high-dose intravenous immunoglobulin
Authors: H-J. Chung, K-Y. Chung
Journal: British Journal of Dermatology (2004)

Sir, Scleromyxoedema‐like cutaneous disease, also called nephrogenic fibrosing dermopathy (NFD), is a new entity described recently. Patients with NFD had undergone haemodialysis, peritoneal dialysis or renal transplant and showed hardened and thickened skin lesions of acute onset localized chiefly to the extremities with resulting flexion contracture of the joints in some cases. Although some of the clinical and histological manifestations of NFD are similar to scleromyxoedema, monoclonal paraproteinaemia and facial involvement were not observed in any patient and there was no evidence of systemic organ involvement.1–6 Because the pathogenesis is unknown and there are no controlled studies of the treatment of NFD, treatment trials have been largely empirical. We report a patient with NFD treated with high‐dose intravenous immunoglobulin (hdIVIg) based on the histopathological similarity between NFD and scleromyxoedema. A 61‐year‐old man was referred with a 4‐month history of skin thickening on both arms and legs and right inguinal area. Clinical examination revealed multiple, hyperpigmented and indurated plaques with a 'peau d'orange' appearance on the surface (Fig. 1A). He showed flexion contracture of the fingers, wrists and elbows on both sides, without pain. He had been on peritoneal dialysis for 8 months, necessitated by an end‐stage renal disease secondary to renal damage triggered by radiocontrast agents. Tests for antinuclear antibody, antidouble‐stranded DNA, antiphospholipid antibody and rheumatoid factor were negative. Serum immunoelectrofixation testing was negative for paraprotein. A 3‐mm punch biopsy taken from a hardened plaque on the right forearm revealed haphazardly arranged dermal fibroblasts associated with thick collagen bundles separated by prominent clefts (Fig. 1B). Alcian blue staining confirmed the presence of interstitial mucin deposition (Fig. 1C) and Verhoeff–van Gieson staining revealed an increased number of thick and thin elastic fibres orientated parallel to the epidermis (Fig. 1D). The CD34+ dendritic network was closely apposed to elastic fibres, and CD68+ mononucleated and multinucleated cells were seen. Based on the above clinical and histological features we diagnosed this condition as NFD. Our patient was treated with hdIVIg 0·4 g kg−1 daily for 5 days each month. For a period of 3 months, the response to treatment was assessed by measuring the range of motion of affected joints. The first cycle was well tolerated and he felt symptomatically better, which correlated well with the improvement of the range of motion measured 1 month later. The ranges of motion of the wrists and hands were improved more than those at other areas. Physical examination revealed that the skin became more lax but he did not show further improvement after the second and third cycles of hdIVIg (Table 1).