tbuckley/cabot-search huggingface dataset:
Identification of novel regulatory factor X (RFX) target genes by comparative genomics in Drosophila species
Authors: Anne Laurençon, Raphaëlle Dubruille, Evgeni Efimenko, Guillaume Grenier, Ryan Bissett, Elisabeth Cortier, Vivien Rolland, Peter Swoboda, Bénédicte Durand
Journal: Genome biology (2007)

Regulatory factor X (RFX) transcription factors play a key role in ciliary assembly in nematode, Drosophila and mouse. Using the tremendous advantages of comparative genomics in closely related species, we identified novel genes regulated by dRFX in Drosophila. We first demonstrate that a subset of known ciliary genes in Caenorhabditis elegans and Drosophila are regulated by dRFX and have a conserved RFX binding site (X-box) in their promoters in two highly divergent Drosophila species. We then designed an X-box consensus sequence and carried out a genome wide computer screen to identify novel genes under RFX control. We found 412 genes that share a conserved X-box upstream of the ATG in both species, with 83 genes presenting a more restricted consensus. We analyzed 25 of these 83 genes, 16 of which are indeed RFX target genes. Two of them have never been described as involved in ciliogenesis. In addition, reporter construct expression analysis revealed that three of the identified genes encode proteins specifically localized in ciliated endings of Drosophila sensory neurons. Our X-box search strategy led to the identification of novel RFX target genes in Drosophila that are involved in sensory ciliogenesis. We also established a highly valuable Drosophila cilia and basal body dataset. These results demonstrate the accuracy of the X-box screen and will be useful for the identification of candidate genes for human ciliopathies, as several human homologs of RFX target genes are known to be involved in diseases, such as Bardet-Biedl syndrome.
Human Embryonic Stem Cells and Gene Therapy
Authors: Yael Strulovici, Philip L Leopold, Timothy P O'Connor, Robert G Pergolizzi, Ronald G Crystal
Journal: Molecular Therapy (2007)

Human embryonic stem cells (hESCs) theoretically represent an unlimited supply of normal differentiated cells to engineer diseased tissues to regain normal function. However, before hESCs can be useful as human therapeutics, technologies must be developed to provide them with the specific signals required to differentiate in a controlled fashion, to regulate and/or shut down the growth of hESCs and their progeny once they have been transferred to the recipient, and to circumvent the recognition of non-autologous hESC-derived cells as foreign. In the context that gene therapy technologies represent strategies to deliver biological signals to address all of these challenges, this review sets out a framework for combined gene transfer/hESC therapies. We discuss how hESCs are derived, characterized, and differentiated into specific cell lineages, and we summarize the characteristics of the 500 hESC lines reported to date. The successes and failures of gene transfer to hESCs are reviewed for both non-viral and viral vectors, as are the challenges to successful use of gene transfer in developing hESC therapy. We also consider gene transfer as a means of facilitating growth and isolation of genetically modified hESCs and as a mechanism for mitigating adverse effects associated with administration of hESCs or their derivatives. Finally, we evaluate the challenges that are likely to be encountered in translating the promise of hESCs to the clinic.
Researchers Exploring Faster Alternatives to 2-Year Test for Carcinogenicity
Authors: Charlie Schmidt
Journal: JNCI Journal of the National Cancer Institute (2006)

KEYWORDS - CLASSIFICATION: Animals;Animals,Laboratory;biomarkers of exposure & effect: validation;Carcinogenicity Tests;Carcinogens;Female;metabolism;methods;Male;Mice;Pharmaceutical Preparations;Predictive Value of Tests;Prognosis;Rats;standards;Species Specificity;trends;Time Factors;Tumor Markers,Biological;United States;United States Environmental Protection Agency;United States Food and Drug Administration.
Cytochromes CYP1A1 and CYP1B1: new pieces in the puzzle to understand the biomechanical paradigm of atherosclerosis
Authors: R. De Caterina, R. Madonna
Journal: Cardiovascular Research (2008)

Atherosclerosis is epidemiologically linked and causally related to the presence of ‘risk factors’. Despite their diversity, major risk factors for cardiovascular disease such as hypercholesterolaemia, diabetes, hypertension, physical inactivity, obesity, and tobacco smoking share a common ‘systemic’ mechanism of action, i.e. they act on the entire inner surface of the arterial vascular tree. The cellular and molecular effects of such systemic risk factors, acting through biohumoral mediators, can account for the greater or lesser propensity of different individuals to atherosclerotic vascular disease (the ‘biohumoral’ paradigm).1,2 Atherosclerosis is, however, focal and discrete in location and has clear preferences for certain sites of the vasculature, such as branching points, bifurcations, or the convex side of curved arteries. In addition, some arteries are more prone to atherosclerosis than others (e.g. the carotid artery vs. the subclavian artery, epicardial coronary arteries vs. intramyocardial arteries), and there are preferential locations even within extremely close areas in the same artery, such as in the region of the carotid bifurcation. The ‘site-specific’ location of the process is a golden opportunity, and perhaps a ‘Holy Grail’ for atherosclerosis research. It is usually explained by the action of particular types of shear stress imposed on the arterial wall by flow regimens of the circulating blood.3 In recent years, much progress has been gained in understanding how shear stress is transduced within the artery wall in order to protect from or promote atherogenesis (the ‘biomechanical’ paradigm). Crucial to this understanding is the identification of endothelial responses to shear stress, by which endothelial cells can sense and integrate haemodynamic stimuli and react to them.

The arterial endothelium is exposed to three main varieties of haemodynamic forces:4,5 (a) the pressure generated by hydrostatic forces towards the vessel wall; (b) circumferential tensions or stress, resulting from … 

*Corresponding author. Tel: +39 0871 415 12; fax: +39 0871 402 817. E-mail : rdecater{at}unich.it
Tissue-specific and high-level expression of the human tyrosine hydroxylase gene in transgenic mice
Authors: Norio Kaneda, Toshikuni Sasaoka, Kazuto Kobayashi, Kazutoshi Kiuchi, Ikuko Nagatsu, Yoshikazu Kurosawa, Keisuke Fujita, Minesuke Yokoyama, Tatsuji Nomura, Motoya Katsuki, Toshiharu Nagatsu
Journal: Neuron (1991)
The endothelium at the brink of calamity in storage disease: more than just overloaded with junk?
Authors: C. de Wit
Journal: Cardiovascular Research (2010)

This editorial refers to ‘Globotriaosylceramide leads to KCa3.1 channel dysfunction: a new insight into endothelial dysfunction in Fabry disease’ by S. Park et al ., pp. 290–299, this issue.

The endothelium crucially controls the contractile status of vascular smooth muscle and thereby vascular diameter. This is achieved by the release of dilating endothelial autacoids such as nitric oxide (NO), prostaglandins, and a third factor that elicits relaxation through smooth muscle hyperpolarization and is therefore known as ‘endothelium-derived hyperpolarizing factor’ (EDHF). Although the importance of EDHF is well accepted, its chemical nature is still elusive, and a wide range of agents, such as K+ ions, eicosanoids, H2O2, H2S, or C-type natriuretic peptide, have been suggested to serve as EDHF. Despite this diversity, it is firmly established that endothelial hyperpolarization is critical to initiate EDHF-type dilation. It is either achieved by releasing one of the above-mentioned molecules or by a direct current transfer from endothelium to smooth muscle via the gap junctions that interconnect these cells.1 The initial endothelial hyperpolarization results from opening of Ca2+-activated K+-channels (KCa), which have been identified as KCa3.1 and/or KCa2.3 (also named IKCa and SKCa, respectively) by pharmacological blockers as well as by genetic approaches. Both endothelial KCa channels are activated by Ca2+ and are voltage independent, which is an important biophysical feature that prevents their inactivation by the ensuing hyperpolarization, thus …
The silver lining
Authors: L. Farrell
Journal: BMJ (2009)

Each September, at Croke Park, when the ball is thrown in at the all Ireland Gaelic football final, every true Irishman’s heart beats a little faster. It is our spiritual home, but for many years it had been a bitter vale of tears for County Armagh.

Until 2002. That year our team had a vigour, a sense of purpose—maybe this year would be different, maybe this year we would take the Sam Maguire Cup home for the very first time.

Orange and white flags and …
Decreased intercellular coupling after prolonged rapid stimulation in rabbit atrial muscle.
Authors: J Bredikis, F Bukauskas, R Veteikis
Journal: Circulation Research (1981)

Driving rabbit atrial trabeculae at a rapid rate for 15 minutes resulted in a decrease in the space constant for electrotonic decay from an average of 670 to 440 micrometers. Input resistance, Rin, as measured by use of a double-barrelled microelectrode, increased from a mean value of 380 kOhms to one of 600 kOhms. The time to return to control values after the end of rapid driving was 20-60 minutes. Similar effects of rapid driving were observed in the presence of atropine, propranolol, and atropine plus propranolol and phentolamine. According to the theory of current spread in a three-dimensional syncytium, a rise of input resistance should be interpreted mainly as an increase of cell-to-cell resistance. We advance the hypothesis that, when driven at their maximal possible rate (or when fibrillating), cardiac cells gain Na+ ad Ca2+, and that this results in partial but reversible uncoupling.
Antigen-presenting capacity of alveolar macrophages and monocytes in pulmonary tuberculosis
Authors: Y Ina, K Takada, M Yamamoto, M Morishita, K Yoshikawa
Journal: European Respiratory Journal (1991)

Using purified protein derivative of tuberculin (PPD) as an antigen, antigen-presenting capacity by monocytes (Mo) and alveolar macrophages (AM) was determined in 17 patients with pulmonary tuberculosis and nine healthy controls. All of the patients and healthy controls were positive for PPD skin test. Although Mo obtained from both the control and tubercular subjects revealed antigen-presenting capacity to autologous blood T-lymphocytes, no significant difference was observed between the two groups. In contrast, AM obtained from the tubercular patients, but not from the controls, showed antigen-presenting capacity to autologous blood T-lymphocytes and to lung T-lymphocytes. No significant difference was shown in HLA-DR antigen expression on AM between the control and tubercular patients. Besides, the exogenous addition of interleukin-1 (IL-1) did not induce antigen-presenting capacity by AM obtained from the controls. These results suggest that neither increased HLA-DR antigen expression on AM nor an increased release of IL-1 from AM is responsible for the enhanced antigen-presenting capacity in tuberculosis.
MACROPHAGE-LYMPHOCYTE CLUSTERS IN THE IMMUNE RESPONSE TO SOLUBLE PROTEIN ANTIGEN IN VITRO
Authors: Morten H. Nielsen, Henning Jensen, Otto Brændstrup, Ole Werdelin
Journal: The Journal of Experimental Medicine (1974)

Macrophage-lymphocyte clusters are formed when lymph node cells and autologous peritoneal exudate cells from guinea pigs immunized with tubercle bacilli are cultured in the presence of purified protein derivative of tuberculin (PPD) for 20 h. We have studied the ultrastructure of these clusters employing transmission and scanning electron microscopy. The most simple macrophage-lymphocyte cluster consisted of one macrophage, one large central lymphocyte with a blastoid appearance attached to the macrophage with a broad area of contact, and from a few to more than 20 small peripheral lymphocytes attached to the central lymphocyte by their uropods. Some clusters were of more complex type, containing two or three macrophages or one macrophage with more than one central lymphocyte attached to the surface, but even in these clusters each peripheral lymphocyte was attached only to one central lymphocyte. By morphological criteria the peripheral lymphocytes were T lymphocytes.
Hox Gene Clusters of Early Vertebrates: Do They Serve as Reliable Markers for Genome Evolution?
Authors: Shigehiro Kuraku
Journal: Genomics Proteomics & Bioinformatics (2011)

Abstract Hox genes, responsible for regional specification along the anteroposterior axis in embryogenesis, are found as clusters in most eumetazoan genomes sequenced to date. Invertebrates possess a single Hox gene cluster with some exceptions of secondary cluster breakages, while osteichthyans (bony vertebrates) have multiple Hox clusters. In tetrapods, four Hox clusters, derived from the so-called two-round whole genome duplications (2R-WGDs), are observed. Overall, the number of Hox gene clusters has been regarded as a reliable marker of ploidy levels in animal genomes. In fact, this scheme also fits the situations in teleost fishes that experienced an additional WGD. In this review, I focus on cyclostomes and cartilaginous fishes as lineages that would fill the gap between invertebrates and osteichthyans. A recent study highlighted a possible loss of the HoxC cluster in the galeomorph shark lineage, while other aspects of cartilaginous fish Hox clusters usually mark their conserved nature. In contrast, existing resources suggest that the cyclostomes exhibit a different mode of Hox cluster organization. For this group of species, whose genomes could have differently responded to the 2R-WGDs from jawed vertebrates, therefore the number of Hox clusters may not serve as a good indicator of their ploidy level.
Genetic Pathways and New Progression Markers for Prostate Cancer Suggested by Microsatellite Allelotyping
Authors: Rolf von Knobloch, Lutz Konrad, Peter J. Barth, Heidrun Brandt, Sebastian Wille, Axel Heidenreich, Roland Moll, Rainer Hofmann
Journal: Clinical Cancer Research (2004)

Abstract Purpose: At diagnosis, the biological behavior of prostate cancer is uncertain, making the choice of an adequate therapy option difficult. Performing microsatellite allelotyping on a large series of consecutive prostate cancers procured during radical prostatectomy at our institution, we sought to identify molecular markers associated with disease progression. Experimental Design: A total of 156 consecutive fresh tumor samples was prospectively collected and macroscopically dissected from the whole prostatectomy specimen immediately after operation. Histologically 100 samples contained &amp;gt;75% tumor cells and were therefore enrolled in the microsatellite allelotyping, using a total of 24 polymorphic markers for the chromosomal regions 5p, 5q, 7q, 8p, 9p, 9q, 13q, 17p, 17q, and 18q. Fresh paired normal and tumor DNA was investigated in fluorescent microsatellite analysis with automated laser product detection. Results: The incidence of tumor–DNA alterations [loss of heterozygosity or allelic imbalance (AI)] was highest for chromosomal regions 13q and 8p with 72 and 71%, respectively, followed by chromosomes 7q, 18q, 5q, and 17p with 57, 53, 41, and 39%, respectively. Alterations at chromosomes 8p, 9p, 13q, and 17p were significantly (P &amp;lt; 0.05) associated with advanced tumor stage, whereas AI at 8p and 17p was also associated with high Gleason score (P &amp;lt; 0.05). AI at 5q and 9p was associated with regional lymph node metastasis (P &amp;lt; 0.05). The combination of AI at 8p and 13q was strongly associated with advanced tumor stage (P &amp;lt; 0.0001). Conclusions: With the obtained results, we are able to postulate three distinct pathways in prostate carcinogenesis, and we identified microsatellite markers of prognostic value.
A Lecture on Partial Pyloric Obstruction: Being an Abstract of the Third of the James Watson Lectures on "Some Chronic Gastric Disorders"
Authors: A. E. Maylard
Journal: BMJ (1920)

THE causes of pyloric obstruction may be primarily classified into anatomical and pathological; and the latter may be subelassified into (1) those dependent on inflamma- tion and (2) those the result of new growths.
Interleukin 16 and T-cell Chemoattractant Activity in Bronchoalveolar Lavage 24 Hours after Allergen Challenge in Asthma
Authors: NORBERT KRUG, WILLIAM W. CRUIKSHANK, THOMAS TSCHERNIG, VEIT J. ERPENBECK, KERSTIN BALKE, JENS M. HOHLFELD, DAVID M. CENTER, HELMUT FABEL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

IL-16 has been shown to be one of the earliest CD4+ cell chemoattractants present in BAL 4–6 h after antigen challenge but little is known about its persistence and biological activity after 6 h. We determined the concentration of IL-16 using ELISA and the T-cell chemoattractant activity using a modified Boyden chamber assay in unconcentrated BAL fluid from 13 patients with mild asthma and 9 nonatopic control subjects at baseline and 24 h after segmental allergen or saline challenge. Furthermore, the percentage of IL-16-producing T cells was determined in the different samples of BAL fluid using a flow cytometric intracellular cytokine assay. Although no substantial levels of IL-16 protein were detectable in BAL fluid from control subjects and patients with asthma at baseline and after saline challenge, IL-16 concentrations were significantly elevated in patients with asthma after allergen challenge (median, 97 pg/ml; range, 38–362 pg/ml; p < 0.01). Furthermore, there was an increased T-cell chemoattractant activity after allergen challenge in patients with asthma (p < 0.01), which could be blocked by preincubation with anti-IL-16 antibodies and which correlated significantly with the IL-16 protein levels (R = 0.90, p < 0.01) and with the level of Fas ligand expression on BAL CD4+ cells (R = 0.80, p < 0.05). A high percentage (mean 70–90%) of CD4+ and CD8+ cells stained positively for IL-16 in both patients with asthma and control subjects without differences after allergen or saline challenge. These data demonstrate that the increased chemotactic activity for T cells in patients with asthma is mainly attributable to IL-16. Although T cells by themselves are able to produce IL-16, other cells, such as epithelial cells, have to be considered as further sources for this cytokine in patients with asthma.
A randomized, phase II trial of two dose schedules of carboplatin/paclitaxel/cetuximab in stage IIIB/IV non-small-cell lung cancer (NSCLC)
Authors: M.A. Socinski, M.N. Saleh, D.F. Trent, T.W. Dobbs, L.M. Zehngebot, M.A. Levine, R. Bordoni, P.J. Stella
Journal: Annals of Oncology (2009)
Periostitis in Secondary Syphilis: A Place for Bone Scintigraphy
Authors: K Veerapen, F E Bruckner, J P Halsey, F Davidson, A Saeed
Journal: Journal of the Royal Society of Medicine (1985)

Two cases of secondary syphilis are reported with periostitis as the main presenting feature. Technetium-99m bone scintigraphy was found to be superior to radiography in both defining the extent of involvement and in picking up early lesions.
Sublingual desensitization for buprenorphine hypersensitivity
Authors: Lisa M. Stutius, Itai Pessach, Joanne Lee, Mindy S. Lo, Sharon Levy, Patricia Schram, Miriam Schizer, Jackson Wong, Wanda Phipatanakul, Dale T. Umetsu
Journal: Journal of Allergy and Clinical Immunology (2010)
International Aeromedical Evacuation
Authors: Peter G. Teichman, Yoel Donchin, Raphael J. Kot
Journal: New England Journal of Medicine (2007)

Thousands of international aeromedical evacuations are conducted every year. An increasing number of travelers are elderly or have chronic illnesses, and there is more travel to regions where road trauma and infectious diseases are endemic but dependable medical care is not available. This review explains the indications for aeromedical evacuation, as well as the logistics, safety considerations, and principles of in-flight care for sick or injured patients.
Therapeutic Strategies for Metastatic Colorectal Cancer: Simultaneous, Sequential, or Specific?
Authors: Mace L. Rothenberg, Jordan D. Berlin
Journal: Journal of Clinical Oncology (2003)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.07.941 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12963700 Therapeutic Strategies for Metastatic Colorectal Cancer: Simultaneous, Sequential, or Specific? Mace L. RothenbergxMace L. RothenbergSearch for articles by this author , Jordan D. BerlinxJordan D. BerlinSearch for articles by this author Show More Vanderbilt-Ingram Cancer Center, Nashville, TN https://doi.org/10.1200/JCO.2003.07.941 Full Text PDF Figures and Tables "Therapeutic Strategies for Metastatic Colorectal Cancer: Simultaneous, Sequential, or Specific?." Journal of Clinical Oncology, 21(20), pp. 3716–3717© 2003 by American Society of Clinical Oncology
The ABCD of GOLD made clear
Authors: Peter M.A. Calverley
Journal: European Respiratory Journal (2013)

Data supporting the new GOLD COPD classification works but may lead to too rigid a segregation of patient groups http://ow.ly/nMoXnChronic obstructive pulmonary disease (COPD) remains a major public health problem.We know this with some certainty from the recently published Global Burden of Disease Study [1], a remarkable analysis of 235 causes of death in 21 regions of the world over a 30-year period.These data show that COPD will rise from the fourth most common cause of death in 1990 to the third by 2020.This gloomy prognostication fits with US data showing a progressive age-specific rise in mortality from COPD in both males and females over the last 50 years [2].The challenge that COPD presents has been met by a dramatic increase in COPD-related research papers, which range from studies identifying airway loss in spirometrically mild disease [3], to improvements in case finding using the peak expiratory flows as screening tool [4], and to new antiinflammatory drugs and bronchodilators to diminish the symptom burden of this condition [5][6][7].Marshalling this mass of information into a clinically useful format for patient care has fallen to those clinicians and methodologists who develop treatment guidelines and there is no shortage of these in the field of COPD.The first COPD guidelines were produced by both national and international societies with the joint American Thoracic Society (ATS)/European Respiratory Society (ERS) document [8] proving to be particularly influential.However, the rise of evidence-based medicine has had the unanticipated effect of decreasing the scope of guidance for COPD, which is now almost entirely focused on the relative merits of drug treatment as this is where the most robust clinical trial data are available [9].