tbuckley/cabot-search huggingface dataset:
Nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of lens proteins in experimental sugar cataracts.
Authors: V M Monnier, V J Stevens, A Cerami
Journal: The Journal of Experimental Medicine (1979)

The formation of sugar-cataracts has been hypothesized to involve the nonenzymatic glycosylation, sulfhydryl oxidation, and aggregation of lens proteins. Cataractous lenses of diabetic and galactosemic rats were analyzed for glycosylated lysine residues in crystallins. A five- and a ten-fold increase in glycosylated lysine residues was measured in galactose and diabetic cataracts, respectively. The modification was predominant in the insoluble fraction of the lens homogenate. The proteins were further examined for the presence of disulfide bonds and high molecular weight aggregates. After careful disruption of the lens in a nitrogen environment, a cloudy solution was obtained from cataractous lenses whereas a clear solution was obtained from normal lenses. The absorbance at 550 nm of the solution of both the galactosemic and the diabetic cataracts could be decreased by approximately 50% with the addition of dithioerythritol (50 mM). The presence of high molecular weight aggregates was ascertained by sucrose gradient centrifugation and gel filtration chromatography. The proteins were heterogenous in size and showed a mol wt range of 36 to greater than 176 million daltons. Treatment with dithioerythritol induced a marked decrease in the amount of high molecular weight proteins. These data suggest that sugar cataracts of experimental animals have, in common with human cataracts, the presence of high molecular weight aggregates which are in part linked by disulfide bonds.
Receptors of the enteric nervous system: potential targets for drug therapy
Authors: J Tack
Journal: Gut (2000)

<h3>Background</h3> Inhaled colistin (IC) is formally indicated to treat <i>Pseudomonas aeruginosa</i> bronchial infections in cystic fibrosis (CF) patients. In patients without CF it is not indicated and must be prescribed off-label if they have pseudomonas-infected bronchiectasis. <h3>Purpose</h3> To evaluate the way inhaled colistin is used, its effectiveness and economic impact for patients who do not have CF in our hospital. <h3>Materials and methods</h3> Retrospective study. 24 patients’medical records were evaluated. All of them were undergoing IC treatment for their PA colonised bronchiectasis for at least 6 months from January 2011 to January 2013 in our hospital. None of them was diagnosed with CF. Besides demographics, the frequency and duration of hospitalisation for respiratory exacerbations and emergency episodes were counted in each patient before and after colistin intensive treatment. These two values were considered as efficacy parameters. Data were compared using a student’s t test for paired samples. Regarding the cost analysis, only hospitalisation-related expenditure and inhaled colistin treatment costs were included. Neither concomitant antibiotic treatment, nor expenditure related to medical consultations were measured. <h3>Results</h3> 13 patients were female and mean age was 74.8. Mean treatment duration was 16.56 months and mean colistin expenditure was 7,504.44 € per patient. Average number of hospital admissions before treatment was 1.52 per patient with a mean duration of 8.37 days. These were reduced after treatment, with 0.79 hospitalisations per patient with a mean duration of 5.45 days. This generated savings of 1402.9 € per patient overall. The emergency episodes also decreased from 1.87 to 1.45. Although these differences showed clinical relevance, they did not reach statistical significance. <h3>Conclusions</h3> Though the limited sample size does not enable us to demonstrate the real difference, inhaled colistin may be considered a cost-effective option to treat patients with pseudomonas-infected bronchiectasis but no CF. No conflict of interest.
Improved Expression and Reactivity of Transduced Tumor-Specific TCRs in Human Lymphocytes by Specific Silencing of Endogenous TCR
Authors: Sachiko Okamoto, Junichi Mineno, Hiroaki Ikeda, Hiroshi Fujiwara, Masaki Yasukawa, Hiroshi Shiku, Ikunoshin Kato
Journal: Cancer Research (2009)

Adoptive T-cell therapy using lymphocytes genetically engineered to express tumor antigen-specific TCRs is an attractive strategy for treating patients with malignancies. However, there are potential drawbacks to this strategy: mispairing of the introduced TCR alpha/beta chains with the endogenous TCR subunits and competition of CD3 molecules between the introduced and endogenous TCRs can impair cell surface expression of the transduced TCR, resulting in insufficient function and potential generation of autoreactive T cells. In addition, the risk of tumor development following the infusion of cells with aberrant vector insertion sites increases with the vector copy number in the transduced cells. In this study, we developed retroviral vectors encoding both small interfering RNA constructs that specifically down-regulate endogenous TCR and a codon-optimized, small interfering RNA-resistant TCR specific for the human tumor antigens MAGE-A4 or WT1. At low copy numbers of the integrated vector, the transduced human lymphocytes exhibited high surface expression of the introduced tumor-specific TCR and reduced expression of endogenous TCRs. In consequence, the vector-transduced lymphocytes showed enhanced cytotoxic activity against antigen-expressing tumor cells. Therefore, our novel TCR gene therapy may open a new gate for effective immunotherapy in cancer patients.
Gastroenterology research in the United Kingdom: funding sources and impact
Authors: G Lewison
Journal: Gut (1998)

Aims —To determine the sources of funding for UK gastroenterology research papers and the relative impact of papers funded by different groups and of unfunded ones. Methods —UK gastroenterology papers from 1988–94 were selectively retrieved from the Science Citation Index by means of a specially constructed filter based on their title keywords and journal names. They were looked up in libraries to determine their funding sources and these, together with their numbers of authors, numbers of addresses, and research category (clinical/basic) were considered as input parameters to the research. Output parameters analysed were mean journal impact category, citation counts by papers, and the frequency of citation by a US patent. Results —Gastroenterology papers comprise about 7% of all UK biomedical research and 46% of them have no acknowledged funding source. One quarter of the papers acknowledged government support, and a similar fraction a private, non-profit source; 11% were funded by the pharmaceutical industry. The papers acknowledging funding had significantly more impact than the others on all three measures. The citing patents had six times more UK inventors than the average for all US Patent and Trademark Office patents in the relevant classes and were mostly generic in application. Conclusion —The variation in impact of papers funded by different sources can mostly be explained by a simple model based on the input factors (numbers of funding bodies, numbers of authors, numbers of addresses, and research type). The national science base in gastroenterology is important for the underpinning of UK invented patents citing to it.
A tumor-associated antigen specific for human kappa myeloma cells.
Authors: H A Boux, R L Raison, K Z Walker, G E Hayden, A Basten
Journal: The Journal of Experimental Medicine (1983)

A monoclonal antibody (K-1-21) raised against a kappa Bence Jones protein exhibits unique binding properties to malignant plasma cells. K-1-21 is an IgG1 kappa antibody that reacts with human kappa light chains in free form, but shows no reactivity with heavy chain-associated kappa light chains. By immunofluorescence, K-1-21 binds to the surface of LICR LON/HMy2 (HMy2) kappa myeloma cells and to plasma cells from a majority (8/11) of patients with various types of kappa myeloma; it did not bind to the surface of normal cells, nor to malignant cells of non-kappa myeloma origin. Flow cytometry analysis of K-1-21 binding to HMy2 cells indicated that the surface reactivity of K-1-21 could be completely inhibited by preincubation of the antibody with purified kappa light chains, whereas no inhibition occurred after preincubation with lambda chains or intact human IgG. Thus, the epitope recognized by K-1-21 on the cell surface may be similar, if not identical, to the determinant recognized on soluble free kappa light chains, and constitutes a tumor-associated antigen with selectivity for kappa myeloma cells. K-1-21 may therefore have clinical potential in patients with kappa myeloma.
pH in Expired Breath Condensate of Patients with Inflammatory Airway Diseases
Authors: Konstantinos Kostikas, Georgios Papatheodorou, Konstantinos Ganas, Konstantinos Psathakis, Panos Panagou, Stelios Loukides
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Endogenous airway acidification, as assessed by pH in expired breath condensate, has been implicated in asthma pathophysiology. We measured pH in breath condensate of patients with inflammatory airway diseases in stable condition and examined its relationship with the inflammatory process (as assessed by differential cell counts in induced sputum), oxidative stress (as assessed by H2O2 and 8-isoprostane), and nitric oxide metabolism (as assessed by total nitrate/nitrite). We studied 40 patients with bronchial asthma (20 with moderate disease, forced expiratory volume in 1 second 60 [10]% SD predicted), 20 patients with bronchiectasis, 20 patients with chronic obstructive pulmonary disease (COPD), and 10 normal subjects. Mean (95% confidence intervals) pH values were significantly lower in patients with COPD and bronchiectasis compared with patients with asthma and control subjects (7.16, 7.09–7.23 and 7.11, 7.04–7.19 versus 7.43, 7.35–7.52 and 7.57, 7.51–7.64, respectively, p < 0.0001). Patients with moderate asthma had significantly lower values compared with mild and control subjects. In patients with COPD and bronchiectasis, the values of pH were significantly correlated with both sputum neutrophilia and oxidative stress. Respectively, in patients with moderate asthma, a significant correlation was observed between pH and sputum eosinophilia, total nitrate/nitrite, and oxidative stress. The pH of the expired breath condensate might be a simple, noninvasive, inexpensive, and easily repeatable procedure for the evaluation of the inflammatory process in airway diseases.
Chronic intestinal pseudoobstruction and ophthalmoplegia in a patient with mitochondrial myopathy.
Authors: R Cervera, J Bruix, A Bayes, R Blesa, I Illa, J Coll, A M Garcia-Puges
Journal: Gut (1988)

A 38 year old woman having chronic intestinal pseudoobstruction associated with mitochondrial myopathy is reported. The clinical and radiographic features suggested the diagnosis of chronic intestinal pseudoobstruction. Muscular atrophy and ophthalmoplegia led to muscle biopsy, which disclosed accumulation of normal and abnormal mitochondria ('ragged red fibres'), characteristic of mitochondrial myopathy.
The RhoGAP Protein DLC-1 Functions as a Metastasis Suppressor in Breast Cancer Cells
Authors: Steve Goodison, Jing Yuan, Derek Sloan, Ryung Kim, Cheng Li, Nicholas C. Popescu, Virginia Urquidi
Journal: Cancer Research (2005)

Abstract The identification of molecular signatures characteristic of tumor cells that are capable of metastatic spread is required for the development of therapeutic interventions to abrogate this lethal process. To facilitate this, we have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 are spontaneously occurring sublines of the MDA-MB-435 cell breast tumor cell line that exhibit phenotypic differences in growth, invasion, and metastatic efficiency in athymic mice. In this study, transcriptional profiles of these cell lines were created using oligonucleotide microarrays representing over 12,000 genes. Intensity modeling and hierarchical clustering analysis identified a 171-gene expression signature that correlated with metastatic phenotype and highlighted several GTPase signaling components. Restoration of one of these GTPases, deleted in liver cancer-1 (DLC-1), in metastatic M4A4 cells to levels observed in the nonmetastatic NM2C5 cell line resulted in the inhibition of migration and invasion in vitro and a significant reduction in the ability of these cells to form pulmonary metastases in athymic mice. These studies show the utility of expression profiling, in an appropriate experimental system, to identify genetic determinants of metastatic sufficiency. The finding that DLC-1 can act as a metastasis-suppressor gene supports an influential role for GTPase signaling in tumor progression.
Genetic Ablation of Cav1 Differentially Affects Melanoma Tumor Growth and Metastasis in Mice: Role of Cav1 in Shh Heterotypic Signaling and Transendothelial Migration
Authors: Franco Capozza, Casey Trimmer, Remedios Castello-Cros, Sanjay Katiyar, Diana Whitaker-Menezes, Antonia Follenzi, Marco Crosariol, Gemma Llaverias, Federica Sotgia, Richard G. Pestell, Michael P. Lisanti
Journal: Cancer Research (2012)

Both cell-autonomous and non-cell-autonomous factors contribute to tumor growth and metastasis of melanoma. The function of caveolin-1 (Cav1), a multifunctional scaffold protein known to modulate several biologic processes in both normal tissue and cancer, has been recently investigated in melanoma cancer cells, but its role in the melanoma microenvironment remains largely unexplored. Here, we show that orthotopic implantation of B16F10 melanoma cells in the skin of Cav1KO mice increases tumor growth, and co-injection of Cav1-deficient dermal fibroblasts with melanoma cells is sufficient to recapitulate the tumor phenotype observed in Cav1KO mice. Using indirect coculture experiments with fibroblasts and melanoma cells combined with cytokine analysis, we found that Cav1-deficient fibroblasts promoted the growth of melanoma cells via enhanced paracrine cytokine signaling. Specifically, Cav1-deficient fibroblasts displayed increased ShhN expression, which heterotypically enhanced the Shh signaling pathway in melanoma cells. In contrast to primary tumor growth, the ability of B16F10 melanoma cells to form lung metastases was significantly reduced in Cav1KO mice. This phenotype was associated mechanistically with the inability of melanoma cells to adhere to and to transmigrate through a monolayer of endothelial cells lacking Cav1. Together, our findings show that Cav1 may regulate different mechanisms during primary melanoma tumor growth and metastatic dissemination.
The Vanilloid Receptor: A Molecular Gateway to the Pain Pathway
Authors: Michael J Caterina, David Julius
Journal: Annual Review of Neuroscience (2001)

The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.
The Influence of Operators On the Obtaining of Successful Bronchial Biopsies in Asthma Research
Authors: Kheem Keem Jones, L.Q.C. Siew, P. Pillai, C. Reinholtz, H. Bull, M. Rabuya, E. Fuerst, D.B. Wright, Y. Shaifta, S. Ying, Q. Meng, C.J. Corrigan
Journal: Journal of Allergy and Clinical Immunology (2013)
Early Adoption and Disturbing Disparities in Sentinel Node Biopsy in Breast Cancer
Authors: S. B. Edge
Journal: JNCI Journal of the National Cancer Institute (2008)

Axillary lymph node surgery remains an integral component of breast cancer treatment. Node status provides key prognostic information that is used to direct adjuvant systemic therapy ( 1 ). Removal of the nodes may also improve local control, although the preponderance of data shows no survival advantage with node dissection itself ( 2 ). Until recently, surgery required full axillary lymph node dissection (ALND). However, recovery from ALND is painful, and the procedure carries the risk of permanent lymphedema. In the early 1990s, it was hypothesized that colloidal material injected into the breast would drain to the same fi rst node(s) as the cancer ( 3 , 4 ). The commonly used agents are radiolabeled sulfur colloid alone or in combination with a blue dye (isosulfan blue or methylene blue), which are detected by a hand-held gamma probe or by visual identifi cation of blue-stained nodes. Early confi rmatory studies proved that this procedure, termed “sentinel lymph node biopsy” (SLNB) for those fi rst nodes “standing guard” in the axilla, was accurate in
Prognostic Relevance of Increased Angiogenesis in Osteosarcoma
Authors: Michael Kreuter, Ralf Bieker, Stefan S. Bielack, Tanja Auras, Horst Buerger, Georg Gosheger, Heribert Jurgens, Wolfgang E. Berdel, Rolf M. Mesters
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose of this work was to evaluate the prognostic relevance of microvessel density (MVD) for response to chemotherapy and long-term outcome in osteosarcoma. Experimental Design: Pretherapeutic tumor biopsies of 60 patients with high-grade central osteosarcoma, who were treated according to multimodal neoadjuvant protocols of the German-Austrian-Swiss Cooperative Osteosarcoma Study Group, were evaluated for intratumoral MVD. MVD was correlated with demographic and tumor-related variables, response, and survival. Results: The median intratumoral MVD was 52 microvessels per 0.26-mm2 field area (interquartile range, 31–77 microvessels per 0.26-mm2 field area). At a median follow-up period of 3.5 years, patients with a high (&amp;gt;median) MVD had significantly higher 5- and 10-year overall survival rates (84%) than patients with low (≤median) MVD (49%; P = 0.0029). Furthermore, increased relapse-free survival for patients with high MVD (P = 0.0064) was observed. In a subgroup analysis of 44 patients with primary high-grade central osteosarcoma of the extremities without primary metastases and good surgical remission, high MVD was associated with 5- and 10-year overall survival rates of 91% compared with 58% for low MVD (P = 0.034). Cox regression analysis revealed that MVD was an independent prognostic factor for survival. A good response to chemotherapy (histologic grading scale of Salzer-Kuntschik) correlated significantly with a high MVD (P = 0.006). Conclusions: Increased angiogenesis is a prognostic indicator for higher survival and response rates to chemotherapy in patients with osteosarcoma. Thus, measurement of MVD might be useful in decisions selecting patients for future neoadjuvant treatment.
Asthma biomarkers: what constitutes a ‘gold standard’?
Authors: Joseph R Arron, Kenji Izuhara
Journal: Thorax (2014)

Many studies have assessed sputum eosinophil percentage as a phenotypic descriptor in asthma patients. Adjusting inhaled corticosteroid (ICS) dose based on sputum eosinophilia can lead to better clinical outcomes than using empirical clinical guidelines alone.1 ,2 While techniques for collecting and analysing sputum eosinophils are available in specialty clinics, sputum analysis remains time consuming, onerous to the patient, labour intensive and is not always successful, which precludes its broader clinical generalisability to primary care settings where most asthma patients are managed. Thus, there is a need for less invasive and more technically straightforward means of phenotyping asthma patients to enable therapeutic management along biological, rather than empirical, guidelines. In particular, accurate phenotyping of severe asthma patients refractory to ICS treatment has proven to be critical for demonstrating the efficacy of emerging experimental therapies that target specific inflammatory pathways.3

Sterk and colleagues compared three biomarkers, peripheral blood eosinophils, fractional exhaled nitric oxide (FeNO) and serum periostin levels, for assessing how reliably each reflects sputum eosinophilia in a cross-sectional study.4 They report that blood eosinophils performed favourably, with a receiver operating characteristic area under the curve of 0.89 in a test cohort and 0.85 in a replication cohort. Using a threshold of 270 eosinophils/μL of blood, they report positive and negative predictive values of 79% and 91% for predicting sputum eosinophilia of ≥3%, which is in line with a recent similar study in Clinical and Experimental Allergy by Zhang and colleagues who identified 260 eosinophils/μL of blood as an optimal cut-off.5 Overall, the finding that blood eosinophil counts are a reasonably accurate biomarker of sputum eosinophil percentage in two rigorously conducted independent studies is encouraging, as blood eosinophil counts are readily obtained from a complete blood count with differential, a test that is convenient and widely available …
Validation of the 2001 St Gallen Risk Categories for Node-Negative Breast Cancer Using a Database From the Spanish Breast Cancer Research Group (GEICAM)
Authors: R. Colomer, G. Viñas, M. Beltran, A. Izquierdo, A. Lluch, A. Llombart-Cussac, E. Alba, B. Munárriz, M. Martín
Journal: Journal of Clinical Oncology (2004)
Rapid, accurate, computational discovery of Rho-independent transcription terminators illuminates their relationship to DNA uptake
Authors: Carleton L Kingsford, Kunmi Ayanbule, Steven L Salzberg
Journal: Genome biology (2007)

Abstract Background In many prokaryotes, transcription of DNA to RNA is terminated by a thymine-rich stretch of DNA following a hairpin loop. Detecting such Rho-independent transcription terminators can shed light on the organization of bacterial genomes and can improve genome annotation. Previous computational methods to predict Rho-independent terminators have been slow or limited in the organisms they consider. Results We describe TransTermHP, a new computational method to rapidly and accurately detect Rho-independent transcription terminators. We predict the locations of terminators in 343 prokaryotic genomes, representing the largest collection of predictions available. In Bacillus subtilis , we can detect 93% of known terminators with a false positive rate of just 6%, comparable to the best-known methods. Outside the Firmicutes division, we find that Rho-independent termination plays a large role in the Neisseria and Vibrio genera, the Pasteurellaceae (including the Haemophilus genus) and several other species. In Neisseria and Pasteurellaceae, terminator hairpins are frequently formed by closely spaced, complementary instances of exogenous DNA uptake signal sequences. We quantify the propensity for terminators to include these sequences. In the process, we provide the first discussion of potential uptake signals in Haemophilus ducreyi and Mannheimia succiniciproducens , and we discuss the preference for a particular configuration of uptake signal sequences within terminators. Conclusion Our new fast and accurate method for detecting transcription terminators has allowed us to identify and analyze terminators in many new genomes and to identify DNA uptake signal sequences in several species where they have not been previously reported. Our software and predictions are freely available.