tbuckley/cabot-search huggingface dataset:
Sequential nailfold capillary microscopy in scleroderma and related disorders.
Authors: M.L Wong, J Highton, D.G Palmer
Journal: Annals of the Rheumatic Diseases (1988)

Sequential nailfold capillary microscopy was carried out monthly for seven months in seven patients (four with scleroderma, one with dermatomyositis, one with mixed connective tissue disease, and one with limited connective tissue disease). Progressive enlargement of some capillary loops was observed, with a number becoming obliterated, leaving avascular areas. Extravasation from capillaries usually preceded capillary loss. These observations have shown the progressive nature of the nailfold capillary abnormalities associated with these disorders and suggest that capillary enlargement is the result of injury, rather than compensation for capillary loss.
Heparanase, Hyaluronan, and CD44 in Cancers: A Breast Carcinoma Perspective
Authors: Martin Götte, George W. Yip
Journal: Cancer Research (2006)

Abstract Glycosaminoglycans are major constituents of the cancer cell surface and the tumor stroma. The heparan sulfate degrading enzyme heparanase, hyaluronan, and its receptor CD44 are up-regulated in breast cancer, generating a microenvironment that promotes tumor progression and metastasis. Recent experimental and clinical evidence shows that heparanase, hyaluronan, and CD44 regulate cancer cell proliferation, migration, and invasion, as well as tumor-associated angiogenesis and are correlated with patient survival. These findings suggest that they may be used as prognostic factors and targets for breast cancer treatment. (Cancer Res 2006; 66(21): 10233-7)
Sialic Acid Is an Essential Nutrient for Brain Development and Cognition
Authors: Bing Wang
Journal: Annual Review of Nutrition (2009)

The rapid growth of infant brains places an exceptionally high demand on the supply of nutrients from the diet, particularly for preterm infants. Sialic acid (Sia) is an essential component of brain gangliosides and the polysialic acid (polySia) chains that modify neural cell adhesion molecules (NCAM). Sia levels are high in human breast milk, predominately as N-acetylneuraminic acid (Neu5Ac). In contrast, infant formulas contain a low level of Sia consisting of both Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). Neu5Gc is implicated in some human inflammatory diseases. Brain gangliosides and polysialylated NCAM play crucial roles in cell-to-cell interactions, neuronal outgrowth, modifying synaptic connectivity, and memory formation. In piglets, a diet rich in Sia increases the level of brain Sia and the expression of two learning-related genes and enhances learning and memory. The purpose of this review is to summarize the evidence showing the importance of dietary Sia as an essential nutrient for brain development and cognition.
Risk Factors for Sudden Infant Death Syndrome Among Northern Plains Indians
Authors: Solomon Iyasu
Journal: JAMA (2002)

among American Indians is consistently above the national average, primarily due to a higher death rate during the postneonatal period (28-364 days).Sudden infant death syndrome (SIDS) is the leading cause of postneonatal mortality, and until 1997, was also the leading cause of infant mortality among American Indians. 1-3SIDS is defined as the sudden death of an infant younger than 1 year that remains unexplained after a thorough case investigation, including the performance of a complete autopsy, an examination of the death scene, and a review of the infant's clinical history. 4 In 1999, the SIDS rate was 1.5 per 1000 live births for American Indian infants and 0.7 per 1000 live births for all races combined. 5 The Aberdeen Area Indian Health Service (AAIHS), which serves Indian communities in North Dakota, South Dakota, Nebraska, and Iowa, has the highest rate of infant mortality among the Indian Health Service (IHS) areas. 6,7SIDS is the leading cause of infant deaths in the Aberdeen Area, accounting for more than one fourth of the infant deaths and more than half of the postneonatal deaths.Although there was a 42% decline in the SIDS rates for all IHS regions, from 2.77 per 1000 live births in 1992-1994 6 to 1.61 per
The fibrin-derived peptide Bβ15–42 protects the myocardium against ischemia-reperfusion injury
Authors: Peter Petzelbauer, Paula A Zacharowski, Yasuhiro Miyazaki, Peter Friedl, Georg Wickenhauser, Francis J Castellino, Marion Gröger, Klaus Wolff, Kai Zacharowski
Journal: Nature Medicine (2005)
Tobacco Assessment in Actively Accruing National Cancer Institute Cooperative Group Program Clinical Trials
Authors: Erica N. Peters, Essie Torres, Benjamin A. Toll, K. Michael Cummings, Ellen R. Gritz, Andrew Hyland, Roy S. Herbst, James R. Marshall, Graham W. Warren
Journal: Journal of Clinical Oncology (2012)

Purpose Substantial evidence suggests that tobacco use has adverse effects on cancer treatment outcomes; however, routine assessment of tobacco use has not been fully incorporated into standard clinical oncology practice. The purpose of this study was to evaluate tobacco use assessment in patients enrolled onto actively accruing cancer clinical trials. Methods Protocols and forms for 155 actively accruing trials in the National Cancer Institute's (NCI's) Clinical Trials Cooperative Group Program were evaluated for tobacco use assessment at enrollment and follow-up by using a structured coding instrument. Results Of the 155 clinical trials reviewed, 45 (29%) assessed any form of tobacco use at enrollment, but only 34 (21.9%) assessed current cigarette use. Only seven trials (4.5%) assessed any form of tobacco use during follow-up. Secondhand smoke exposure was captured in 2.6% of trials at enrollment and 0.6% during follow-up. None of the trials assessed nicotine dependence or interest in quitting at any point during enrollment or treatment. Tobacco status assessment was higher in lung/head and neck trials as well as phase III trials, but there was no difference according to year of starting accrual or cooperative group. Conclusion Most actively accruing cooperative group clinical trials do not assess tobacco use, and there is no observable trend in improvement over the past 8 years. Failure to incorporate standardized tobacco assessments into NCI-funded Cooperative Group Clinical Trials will limit the ability to provide evidence-based cessation support and will limit the ability to accurately understand the precise effect of tobacco use on cancer treatment outcomes.
Induced Sputum Inflammatory Mediator Concentrations in Chronic Cough
Authors: Surinder S. Birring, Debbie Parker, Christopher E. Brightling, Peter Bradding, Andrew J. Wardlaw, Ian D. Pavord
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Previous studies have shown evidence of airway inflammation in patients with chronic cough and have suggested that the cough may be due to release of tussive mediators and activation of afferent sensory nerve endings. We measured the concentration of various proinflammatory and tussive mediators in induced sputum supernatants from 20 patients with cough variant asthma or eosinophilic bronchitis, 20 patients with nonasthmatic chronic cough, 22 patients with idiopathic chronic cough, and 18 healthy control subjects. We measured histamine, cysteinyl-leukotrienes, prostanoids (prostaglandin D2 and prostaglandin E2), and interleukin-8 by enzyme immunoassay. The median sputum histamine concentrations were significantly higher in patients with idiopathic chronic cough (8.0 ng/ml) and cough variant asthma/eosinophilic bronchitis (10.2 ng/ml) than in normal subjects (2.6 ng/ml; 95% confidence interval of difference from idiopathic chronic cough, 0.8 to 25.8 [p = 0.009] and 95% confidence interval of difference from cough variant asthma/eosinophilic bronchitis, 1.1 to 20.1 [p = 0.01]). Median sputum prostaglandin D2 and prostaglandin E2 concentrations were significantly higher in all categories of chronic cough. Our findings support the view that there is release of inflammatory and tussive mediators in patients with chronic cough and suggest that there might be similarities in the mechanism of cough in a diverse range of conditions.
PWE-055 Endoscopic Ultrasound Guided Radiofrequency Ablation (EUS-RFA) for Pancreatic Ductal Adenocarcinoma
Authors: M Pai, J Yang, X Zhang, Z Jin, D Wang, H Senturk, S Lakhtakia, D N Reddy, M Kahaleh, N Habib, W R Brugge
Journal: Gut (2013)

<h3>Introduction</h3> The five year survival for pancreatic ductal adenocarcinoma (PDAC) is less than 5% in spite of the advances in management of cancers in the last few decades. Even though surgical resection remains the only potentially curative treatment for PDAC, only 10–20% of patients are candidates for pancreatic resection with almost 50% of patients having distant spread of tumour and approximately one-third manifesting locally advanced disease. Kahaleh and colleagues have demonstrated that EUS guided RF ablation (EUS-RFA) of the pancreatic head using Habib EUS-RFA catheter (Emcision Ltd, UK) was well tolerated in 5 Yucatan pigs and with minimal pancreatitis (1). The aim of this report is to outline the feasibility, safety, complications and early results of EUS-RFA using Habib catheter in patients with inoperable PDAC. <h3>Methods</h3> Seven patients underwent EUS-RFA of PDAC. A novel monopolar radiofrequency (RF) catheter (1.2 mm Habib EUS-RFA catheter, Emcision Ltd, London) was placed through a 19 or 22 gauge fine needle aspiration (FNA) needle after FNA was performed. <h3>Results</h3> Seven patients had EUS-RFA of PDAC with a median age of 69 (range 50 – 77) years. There were 3 female and 4 male patients. Five patients had PDAC in the head of pancreas whilst two had in the body of pancreas. RF was applied at 5 watts, 10 watts and 15 watts in an incremental manner in 1, 3 and 3 patients respectively. The median number of applications were 3 (range 2 – 4) and each application was 90 seconds. The EUS-RFA was completed in all patients. The mean size was 35.2mm and the post procedure imaging in 3–6 months showed decrease in size of the lesion in two patients, whilst the lesions were unchanged in the rest of the patients. There were no early complications like injury or perforation of duodenal or gastric wall, bleeding or severe pancreatitis. All patients stayed overnight after the procedure for observation and four were discharged next day and there were no readmissions post procedure due to pain. One patient had mild pancreatitis which settled with conservative management and was discharged 3 days post procedure. <h3>Conclusion</h3> EUS- RFA of PDAC with a novel monopolar RF probe was well tolerated in 7 patients. The initial results suggest that the procedure is technically relatively easy and safe <h3>Disclosure of Interest</h3> M. Pai: None Declared, J. Yang: None Declared, X. Zhang: None Declared, Z. Jin: None Declared, D. Wang: None Declared, H. Senturk: None Declared, S. Lakhtakia: None Declared, D. N. Reddy: None Declared, M. Kahaleh: None Declared, N. Habib Shareholder of: EMcision Limited, London, United Kingdom, Conflict with: Director, EMcision Limited, London, United Kingdom, W. Brugge: None Declared. <h3>Reference</h3> Gaidhane M <i>et.al</i>. Endoscopic Ultrasound-Guided Radiofrequency Ablation (EUS-RFA) of the Pancreas in a Porcine Model. Gastroenterol Res Pract. 2012; 431451.
Studies on the tubulo-glomerular feedback system in the rat. The mechanism of reduction in filtration rate with benzolamide.
Authors: B J Tucker, R W Steiner, L C Gushwa, R C Blantz
Journal: Journal of Clinical Investigation (1978)

The specific mechanism whereby superficial nephron glomerular filtration rate (sngfr) is reduced after the administration of benzolamide, a carbonic anhydrase inhibitor with a primary inhibitory effect in the proximal tubule, have been examined by measuring pertinent pressures, flows, and glomerular permeabilities in the hydropenic Munich-Wistar rat, a strain with surface glomeruli. Because benzolamide decreases absolute proximal reabsorptive rate, the rate of delivery of tubular fluid to the distal nephron should be at least transiently increased and may reduce sngfr by activating the tubulo-glomerular feedback system. Sngfr fell from 29.2+/2.0 to 2.1+/3.1 nl/min (P less than 0.01) after benzolamide (group 1), a percentage reduction equal to kidney glomerular filtration rate and similar to sngfr obtained in collections from distal tubules. Separate studies (group 2) revealed that if transient increases in distal nephron delivery were prevented by insertion of a long oil block in proximal tubules before control, the decrease in sngfr was prevented (30.3+/1.0 vs. 30.3+/1.8 nl/min, P greater than 0.9). In paired "unblocked" nephrons in the same rats, sngfr fell in group 2 (33.0+/1.0 vs. 25.2+/2.3 nl/min, P less than 0.01). In "blocked" nephrons in which sngfr reduction was prevented, the rate of fluid leaving the proximal tubule increased from 16.9+/ to 23.1+/1.0 nl/min (P less than 0.01). In group 1 studies in which sngfr fell and transient increases in flow out of the last segment of the proximal tubule (distal delivery) (approximately equal to 8 nl/min) were not prevented, steady-state distal delivery was unchanged by benzolamide (13.9+/1.1 vs. 14.2+/2.2 nl/min). Also, sngfr returned toward control, pre-benzolamide values, when a proximal oil block was placed for 15 min and the rate of distal delivery reduced after benzolamide administration, which suggests that this activation was reversible. These data suggest that activation of tubulo-glomerular feedback by transient increases in distal delivery was responsible for decreases in sngfr. Analysis of all determinants of glomerular ultra-filtration revealed that the efferent mechanism leading to reduced sngfr after benzolamide was decreased nephron plasma flow (101+/13 vs. 66+/13 nl/min, P less than 0.01). Hydrostatic pressure and the glomerular permeability coefficient did not contribute to reductions in sngfr with benzolamide. Because the rate of distal delivery remained constant in spite of large changes in both sngfr and absolute proximal reabsorptive rate, it is suggested that the rate of distal delivery may be the physiologic entity that is regulated by the tubulo-glomerular feedback system via alterations in sngfr.
<b> <i>trans-</i> </b>3,4,5′-Trihydroxystibene Inhibits Hypoxia-Inducible Factor 1α and Vascular Endothelial Growth Factor Expression in Human Ovarian Cancer Cells
Authors: Zongxian Cao, Jing Fang, Chang Xia, Xianglin Shi, Bing-Hua Jiang
Journal: Clinical Cancer Research (2004)

Abstract trans-3,4,5′-Trihydroxystibene (resveratrol) is a natural product commonly found in the human diet and has been shown recently to have anticancer effects on various human cancer cells. However, the molecular basis for its anticancer action remains to be elucidated. In this study, we investigated the effect of resveratrol on hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression in human ovarian cancer cells A2780/CP70 and OVCAR-3. We found that although resveratrol did not affect HIF-1α mRNA levels, it did dramatically inhibit both basal-level and growth factor-induced HIF-1α protein expression in the cells. Resveratrol also greatly inhibited VEGF expression. Mechanistically, we demonstrated that resveratrol inhibited HIF-1α and VEGF expression through multiple mechanisms. First, resveratrol inhibited AKT and mitogen-activated protein kinase activation, which played a partial role in the down-regulation of HIF-1α expression. Second, resveratrol inhibited insulin-like growth factor 1-induced HIF-1α expression through the inhibition of protein translational regulators, including Mr 70,000 ribosomal protein S6 kinase 1, S6 ribosomal protein, eukaryotic initiation factor 4E-binding protein 1, and eukaryotic initiation factor 4E. Finally, we showed that resveratrol substantially induced HIF-1α protein degradation through the proteasome pathway. Our data suggested that resveratrol may inhibit human ovarian cancer progression and angiogenesis by inhibiting HIF-1α and VEGF expression and thus provide a novel potential mechanism for the anticancer action of resveratrol.
Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets
Authors: T K B Gandhi, Jun Zhong, Suresh Mathivanan, L Karthick, K N Chandrika, S Sujatha Mohan, Salil Sharma, Stefan Pinkert, Shilpa Nagaraju, Balamurugan Periaswamy, Goparani Mishra, Kannabiran Nandakumar, Beiyi Shen, Nandan Deshpande, Rashmi Nayak, Malabika Sarker, Jef D Boeke, Giovanni Parmigiani, Jörg Schultz, Joel S Bader, Akhilesh Pandey
Journal: Nature Genetics (2006)
C<scp>ELL</scp>M<scp>IGRATION IN THE</scp>F<scp>OREBRAIN</scp>
Authors: Oscar Marín, John L.R. Rubenstein
Journal: Annual Review of Neuroscience (2003)

▪ Abstract The forebrain comprises an intricate set of structures that are required for some of the most complex and evolved functions of the mammalian brain. As a reflection of its complexity, cell migration in the forebrain is extremely elaborated, with widespread dispersion of cells across multiple functionally distinct areas. Two general modes of migration are distinguished in the forebrain: radial migration, which establishes the general cytoarchitectonical framework of the different forebrain subdivisions; and tangential migration, which increases the cellular complexity of forebrain circuits by allowing the dispersion of multiple neuronal types. Here, we review the cellular and molecular mechanisms underlying each of these types of migrations and discuss how emerging concepts in neuronal migration are reshaping our understanding of forebrain development in normal and pathological situations.
Genetic Variations and Polymorphisms of G Protein-Coupled Receptors: Functional and Therapeutic Implications
Authors: Brinda K Rana, Tetsuo Shiina, Paul A Insel
Journal: The Annual Review of Pharmacology and Toxicology (2001)

G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) in GPCR loci. In this article, we use a domain-based approach to systematically examine examples of genetic variation in the coding and noncoding regions of GPCR loci. Data to date indicate that residues in GPCRs are involved in ligand binding and coupling to G proteins and that regulation can be altered by polymorphisms. Studies of GPCR polymorphisms have also uncovered the functional importance of residues not previously implicated from other approaches that are involved in the function of GPCRs. We predict that studies of GPCR polymorphisms will have a significant impact on medicine and pharmacology, in particular, by providing new means to subclassify patients in terms of both diagnosis and treatment.
Lipopolysaccharide and the lung: a story of love and hate
Authors: R. Bals
Journal: European Respiratory Journal (2005)

Lipopolysaccharide (LPS) is a major component of the outer membrane of Gram-negative bacteria. LPS is one of the most potent microbial inducers of inflammation and is responsible for many of the deleterious effects of pulmonary infections. In contrast, surfaces of the body are constantly exposed to small amounts of LPS. This interaction appears to stimulate more beneficial, protective mechanisms. Overall, the interactions between LPS and the body are important; however, factors that determine the nature of this response are not known.

LPS is a prototypical pathogen associated molecular pattern (PAMP), a term that was introduced by Janeway and Medzhitov 1, which describes structurally conserved molecules of microorganisms. PAMPs bind to receptors of the innate immune system, consequently called pattern recognition receptors (PRRs). In 1996, the Drosophila protein Toll was shown to be required for flies to mount an effective immune response against the fungus Aspergillus fumigatus . In 1998, toll like receptor (TLR)4 was positionally identified as the LPS receptor and found to be required for mice to effectively respond to Gram-negative bacteria. These findings have guided the field of (innate) immunity over the last few years. Thirteen mammalian TLR analogues have been identified and functionally linked to various processes, ranging from inflammation and infection, to arthrosclerosis and sterile inflammation 2.

In the lung, TLR4 is expressed by several different cell types, including professional host defence (dendritic cells, macrophages) and structural (endothelial and epithelial cells) cells. Animal models and patient studies have proved that TLR4 contributes significantly to the response to inhaled LPS 3, …
Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer's disease: a prospective cohort study
Authors: Victor L Villemagne, Samantha Burnham, Pierrick Bourgeat, Belinda Brown, Kathryn A Ellis, Olivier Salvado, Cassandra Szoeke, S Lance Macaulay, Ralph Martins, Paul Maruff, David Ames, Christopher C Rowe, Colin L Masters
Journal: The Lancet Neurology (2013)
Antigen-specific clonal expansion and cytolytic effector function of CD8+ T lymphocytes depend on the transcription factor Bcl11b
Authors: Shuning Zhang, Mike Rozell, Raj K. Verma, Diana I. Albu, Danielle Califano, Jeffrey VanValkenburgh, Akeel Merchant, Javier Rangel-Moreno, Troy D. Randall, Nancy A. Jenkins, Neal G. Copeland, Pentao Liu, Dorina Avram
Journal: The Journal of Experimental Medicine (2010)

CD8+ T lymphocytes mediate the immune response to viruses, intracellular bacteria, protozoan parasites, and tumors. We provide evidence that the transcription factor Bcl11b/Ctip2 controls hallmark features of CD8+ T cell immunity, specifically antigen (Ag)-dependent clonal expansion and cytolytic activity. The reduced clonal expansion in the absence of Bcl11b was caused by altered proliferation during the expansion phase, with survival remaining unaffected. Two genes with critical roles in TCR signaling were deregulated in Bcl11b-deficient CD8+ T cells, CD8 coreceptor and Plcγ1, both of which may contribute to the impaired responsiveness. Bcl11b was found to bind the E8I, E8IV, and E8V, but not E8II or E8III, enhancers. Thus, Bcl11b is one of the transcription factors implicated in the maintenance of optimal CD8 coreceptor expression in peripheral CD8+ T cells through association with specific enhancers. Short-lived Klrg1hiCD127lo effector CD8+ T cells were formed during the course of infection in the absence of Bcl11b, albeit in smaller numbers, and their Ag-specific cytolytic activity on a per-cell basis was altered, which was associated with reduced granzyme B and perforin.