tbuckley/cabot-search huggingface dataset:
KIBRA Modulates Directional Migration of Podocytes
Authors: Kerstin Duning, Eva-Maria Schurek, Marc Schlu[Combining Diaeresis]ter, Michael Bayer, Hans-Christian Reinhardt, Albrecht Schwab, Liliana Schaefer, Thomas Benzing, Bernhard Schermer, Moin A. Saleem, Tobias B. Huber, Sebastian Bachmann, Joachim Kremerskothen, Thomas Weide, Hermann Pavensta[Combining Diaeresis]dt
Journal: Journal of the American Society of Nephrology (2008)

Asymmetric delivery and distribution of macromolecules are essential for cell polarity and for cellular functions such as differentiation, division, and signaling. Injury of podocytes, which are polarized epithelial cells, changes the dynamics of the actin meshwork, resulting in foot process retraction and proteinuria. Although the spatiotemporal control of specific protein–protein interactions is crucial for the establishment of cell polarity, the mechanisms controlling polarity-dependent differentiation and division are incompletely understood. In this study, yeast two-hybrid screens were performed using a podocyte cDNA library and the polarity protein PATJ as bait. The protein KIBRA was identified as an interaction partner of PATJ and was localized to podocytes, tubular structures, and collecting ducts. The last four amino acids of KIBRA mediated binding to the eighth PDZ domain of PATJ. In addition, KIBRA directly bound to synaptopodin, an essential organizer of the podocyte cytoskeleton. Stable knockdown of KIBRA in immortalized podocytes impaired directed cell migration, suggesting that KIBRA modulates the motility of podocytes by linking polarity proteins and cytoskeleton-associated protein complexes.
Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry
Authors: S Lehmann, A Ravn, L Carlsson, P Antunovic, S Deneberg, L Möllgård, Å Rangert Derolf, D Stockelberg, U Tidefelt, A Wahlin, L Wennström, M Höglund, G Juliusson
Journal: Leukemia (2011)
Vasoactive intestinal peptide receptors in the airways of smokers with chronic bronchitis
Authors: D. Miotto, P. Boschetto, I. Bononi, E. Zeni, G. Cavallesco, L.M. Fabbri, C.E. Mapp
Journal: European Respiratory Journal (2004)

Vasoactive intestinal peptide (VIP) is a neuropeptide involved in the regulation of airway mucus secretion. The biological functions of VIP are mediated through two receptors, the vasoactive intestinal peptide receptor type 1 (VPAC1R) and type 2 (VPAC2R). The aim of this study was to quantify the expression of both VPAC1R and VPAC2R in the central airways of smokers with chronic bronchitis. Surgical specimens were obtained from 33 smokers undergoing thoracotomy for localised pulmonary lesions: 23 smokers with symptoms of chronic bronchitis and 10 asymptomatic smokers with normal lung function. By using immunohistochemical and microscopic analysis, an increased expression of VPAC1R, but not VPAC2R, was found in bronchial epithelium, bronchial glands and vessels of smokers with symptoms of chronic bronchitis compared with asymptomatic smokers. Smokers with symptoms of chronic bronchitis also had an increased number of mononuclear cells positive for both VPAC1R and VPAC2R in the bronchial submucosa. In conclusion, the expression of type 1 and type 2 vasoactive intestinal peptide receptors is increased in the central airways of smokers with chronic bronchitis, suggesting their possible involvement in the pathogenesis of chronic bronchitis.
The <i>Trypanosoma cruzi trans</i>-Sialidase, through Its Cooh-Terminal Tandem Repeat, Upregulates Interleukin 6 Secretion in Normal Human Intestinal Microvascular Endothelial Cells and Peripheral Blood Mononuclear Cells
Authors: Emma Saavedra, Macario Herrera, Wenda Gao, Haruki Uemura, Miercio A. Pereira
Journal: The Journal of Experimental Medicine (1999)

The Trypanosoma cruzi trans-sialidase can sensitize mice to become highly susceptible to T. cruzi invasion, through mechanisms that remain unknown. In pursuing this observation, we found that purified trans-sialidase induces the selective release of biologically active interleukin (IL)-6 in naive human intestinal microvascular endothelial cells (HIMECs), peripheral blood mononuclear cells (PBMCs), and bladder carcinoma cells. The trans-sialidase action was independent of its catalytic activity, as demonstrated with a genetically engineered trans-sialidase mutant, an enzymatically active polypeptide, and cocultures of PBMCs with epimastigotes and trypomastigotes. Instead, the trans-sialidase action was reproduced with a recombinant COOH-terminal tandem repeat and with synthetic peptides modeled on the tandem repeat. Most interesting, HIMECs infected with a trypomastigote population expressing trans-sialidase effectively released IL-6, but did not upon infection with the counterpart trypomastigote population expressing low trans-sialidase levels. IL-6 is a key factor in the regulation and symptom formation of infection caused by several types of viruses, such as HIV and influenza A virus. However, the function of IL-6 in protozoan and other parasitic diseases remains unclear. The unique findings presented here suggest that trans-sialidase is a major inducer of IL-6 secretion in T. cruzi infection, independently of immune cell activation. Such IL-6 secretion might underlie some features of Chagas's disease, such as pyrexia, neuroprotection, and fibrosis, and might result in the undermining of normal acquired immunity against T. cruzi.
Comparison of subcutaneous interferon beta-1a with glatiramer acetate in patients with relapsing multiple sclerosis (the REbif vs Glatiramer Acetate in Relapsing MS Disease [REGARD] study): a multicentre, randomised, parallel, open-label trial
Authors: Daniel D Mikol, Frederik Barkhof, Peter Chang, Patricia K Coyle, Douglas R Jeffery, Steven R Schwid, Bettina Stubinski, Bernard MJ Uitdehaag
Journal: The Lancet Neurology (2008)
A retrotransposon of the non-long terminal repeat class from the human blood fluke Schistosoma mansoni. Similarities to the chicken-repeat-1- like elements of vertebrates
Authors: A C Drew, P J Brindley
Journal: Molecular Biology and Evolution (1997)

The genomes of representative species of fishes, amphibians, and reptiles contain non-long-terminal-repeat (non-LTR) retrotransposons showing strong sequence identity to the chicken repeat 1 (CR1) non-LTR retrotransposon from birds. These nonavian retroelements have been termed CR1-like elements. We have isolated sequences of a non-LTR retrotransposon from the human blood fluke Schistosoma mansoni. These schistosome sequences, which we have termed the SR1 family of non-LTR retrotransposons, contain regions of deduced amino acids characteristic of the CR1-like elements. SR1 elements possess atypical 3' termini consisting of the tandem repeat (AACCATTTG)2 which are similar in structure to the imperfect tandem repeat of the 3' termini of CR1. There are at least 200 copies of SR1 interspersed through the genome of S. mansoni. The structural and amino acid sequence similarities of SR1 with members of the CR1-like elements suggest that the SR1 family belongs to the CR1-like category of non-LTR retrotransposons. Although other non-LTR retrotransposons have been described in invertebrates, this is the first CR1-like element reported from a nonvertebrate taxon, suggesting that the phylogenetic distribution of CR1-like retrotransposons is not restricted to vertebrates.
How Does Multistep Tumorigenesis Really Proceed?
Authors: Christine L. Chaffer, Robert A. Weinberg
Journal: Cancer Discovery (2015)

Abstract Summary: Identifying the cancer cells-of-origin is of great interest, as it holds the potential to elucidate biologic mechanisms inherent in the normal cell state that have been co-opted to drive the oncogenic cell state. An emerging concept, proposed here, states that cancer stem cells, key players in cancer initiation and metastasis, arise when transit-amplifying cells with mutant genomes dedifferentiate and enter the stem cell state. This model contrasts with the notion that cancer stem cells are the direct products of neoplastically transformed normal tissue stem cells. Cancer Discov; 5(1); 22–4. ©2015 AACR.
Factors affecting toxicity, response and progression-free survival in relapsed patients with indolent B-cell lymphoma and mantle cell lymphoma treated with rituximab: a Japanese phase II study
Authors: T. Igarashi, Y. Kobayashi, M. Ogura, T. Kinoshita, T. Ohtsu, Y. Sasaki, Y. Morishima, T. Murate, M. Kasai, N. Uike, M. Taniwaki, Y. Kano, K. Ohnishi, Y. Matsuno, S. Nakamura, S. Mori, Y. Ohashi, K. Tobinai
Journal: Annals of Oncology (2002)
In Vivo Gene Transfer of the O <sub>2</sub> -Sensitive Potassium Channel Kv1.5 Reduces Pulmonary Hypertension and Restores Hypoxic Pulmonary Vasoconstriction in Chronically Hypoxic Rats
Authors: Zlatko I. Pozeg, Evangelos D. Michelakis, M. Sean McMurtry, Bernard Thébaud, Xi-Chen Wu, Jason R.B. Dyck, Kyoko Hashimoto, Shaohua Wang, Rohit Moudgil, Gwyneth Harry, Richard Sultanian, Arvind Koshal, Stephen L. Archer
Journal: Circulation (2003)

Alveolar hypoxia acutely elicits pulmonary vasoconstriction (HPV). Chronic hypoxia (CH), despite attenuating HPV, causes pulmonary hypertension (CH-PHT). HPV results, in part, from inhibition of O2-sensitive, voltage-gated potassium channels (Kv) in pulmonary artery smooth muscle cells (PASMCs). CH decreases Kv channel current/expression and depolarizes and causes Ca2+ overload in PASMCs. We hypothesize that Kv gene transfer would normalize the pulmonary circulation (restore HPV and reduce CH-PHT), despite ongoing hypoxia.Adult male Sprague-Dawley rats were exposed to normoxia or CH for 3 to 4 weeks and then nebulized orotracheally with saline or adenovirus (Ad5) carrying genes for the reporter, green fluorescent protein reporter+/-human Kv1.5 (cloned from normal PA). HPV was assessed in isolated lungs. Hemodynamics, including Fick and thermodilution cardiac output, were measured in vivo 3 and 14 days after gene therapy by use of micromanometer-tipped catheters. Transgene expression, measured by quantitative RT-PCR, was confined to the lung, persisted for 2 to 3 weeks, and did not alter endogenous Kv1.5 levels. Ad5-Kv1.5 caused no mortality or morbidity, except for sporadic, mild elevation of liver transaminases. Ad5-Kv1.5 restored the O2-sensitive K+ current of PASMCs, normalized HPV, and reduced pulmonary vascular resistance. Pulmonary vascular resistance decreased at day 2 because of increased cardiac output, and remained reduced at day 14, at which time there was concomitant regression of right ventricular hypertrophy and PA medial hypertrophy.Kv1.5 is an important O2-sensitive channel and potential therapeutic target in PHT. Kv1.5 gene therapy restores HPV and improves PHT. This is, to the best of our knowledge, the first example of K+ channel gene therapy for a vascular disease.
Changes in the repertoire of peptides bound to HLA-B27 subtypes and to site-specific mutants inside and outside pocket B.
Authors: S Rojo, F García, J A Villadangos, J A López de Castro
Journal: The Journal of Experimental Medicine (1993)

HLA-B27 subtypes share many structural features, including their pocket B, which interacts with a conserved Arg residue at the second position of B*2705-bound peptides. Subtypes differ among each other at other locations in the peptide binding site. In this study, metabolic labeling and radiochemical pool sequencing were used to address the following issues: (a) presence of the Arg 2 (R2) motif among peptides bound to the various HLA-B27 subtypes; (b) influence of mutations inside and outside pocket B on this motif; and (c) the degree of similarity among the peptide pools bound to the various B27 subtypes. Sequencing of Arg-labeled peptide pools extracted from B*2701 to B*2706, and from two site-directed mutants of B*2705 with changes outside pocket B, indicated that all of these molecules bind peptides with Arg at position 2. Peptides from several mutants with changes altering the structure of pocket B, and from one mutant at the pocket B rim, also retained the R2 motif. However, this was absent in the peptide pool extracted from the M45 mutant, in which the negative charge of pocket B, conferred to HLA-B27 by Glu45, was canceled. These results indicate that alterations outside pocket B, and even disruption of the network of hydrogen bonds that stabilizes Arg binding in pocket B, do not impair binding of peptides bearing the R2 motif, but a nonconservative substitution at position 45 does. As a substantial fraction of anti-B*2705 cytotoxic T lymphocyte (CTL) clones crossreact with the M45 mutant (Villadangos, J., B. Galocha, D. López, V. Calvo, and J. A. López de Castro. 1992. J. Immunol. 149:505) this result suggest that determinant mimicry by nonidentical peptides may frequently account for unexpected CTL crossreactions. Metabolic labeling with various other amino acids and radiochemical sequencing revealed similarities, but also substantial differences, among the peptide pools from the various HLA-B27 subtypes. This strongly suggests that many peptides bind to multiple subtypes, but significant subsets of peptides bound to a given HLA-B27 subtype do not bind to other subtypes or do so with greatly altered efficiency. These results indicate the importance of polymorphism outside pocket B in modulating peptide binding to HLA-B27.
Vascular Endothelial Growth Factor Trap-Eye for Macular Edema Secondary to Central Retinal Vein Occlusion
Authors: David Boyer, Jeffrey Heier, David M. Brown, W. Lloyd Clark, Robert Vitti, Alyson J. Berliner, Georg Groetzbach, Oliver Zeitz, Rupert Sandbrink, Xiaoping Zhu, Karola Beckmann, Julia A. Haller
Journal: Ophthalmology (2012)
Randomised controlled trial of effect of high-impact exercise on selected risk factors for osteoporotic fractures
Authors: Ari Heinonen, Pekka Kannus, Harri Sievänen, Pekka Oja, Matti Pasanen, Marjo Rinne, Kirsti Uusi-Rasi, Ilkka Vuori
Journal: The Lancet (1996)
Effect of cisapride on gallbladder motility after extracorporeal shock-wave lithotripsy
Authors: Joël Thorens, Jean F. Schnegg, Reto Brignoli, Florian Froehlich, Jan B. Jansen, Gian Dorta, André L. Blum, Jean J. Gonvers, Michael Fried
Journal: Journal of Hepatology (1995)
Abnormal fibre usage in UC in remission
Authors: Sally L James, Claus T Christophersen, Anthony R Bird, Michael A Conlon, Ourania Rosella, Peter R Gibson, Jane G Muir
Journal: Gut (2014)

<h3>Objective</h3> Colonic fermentation in patients with UC in remission was compared with that in matched healthy subjects on habitual diets and when dietary fibre was increased. <h3>Design</h3> Fibre intake, faecal output of fibre (measured as non-starch polysaccharide (NSP)), starch, microbiota and fermentation products, and whole gut transit time (WGTT) were assessed in association with habitual diet and when dietary intake of wheat bran (WB)-associated fibre and high amylose-associated resistant starch (RS) was increased in an 8-week, randomised, single-blind, cross-over study. <h3>Results</h3> Despite a tendency to lower habitual fibre intake in UC patients, faecal NSP and starch concentrations were threefold higher than in controls, whereas concentrations of phenols and short-chain fatty acids, pH and WGTT were similar. Increasing RS/WB intake was well tolerated. In controls (n=10), it more than doubled faecal NSP and starch excretion (p=0.002 for both), had no effect on NSP usage and reduced WGTT (p=0.024). In UC patients (n=19), high intake of RS/WB tended to normalise gut transit, but did not increase the proportion of NSP fermented. Increasing intake of RS/WB had little effect on faecal fermentation patterns or the structure of the microbiota. However, faeces from the UC cohort had lower proportions of <i>Akkermansia muciniphila</i> and increased diversity within <i>Clostridium cluster XIVa</i> compared to controls. <h3>Conclusions</h3> Gut fermentation of NSP and starch is diminished in patients with UC. This cannot be explained by abnormal gut transit and was not corrected by increasing RS/WB intake, and may be due to abnormal functioning of the gut microbiota. <h3>Trial registration number</h3> Australian New Zealand Clinical Trials Registry: ACTRN12614000271606.
Glioblastoma Resistance to Anti-VEGF Therapy: Has the Challenge Been MET?
Authors: Joseph H. McCarty
Journal: Clinical Cancer Research (2013)

Abstract In glioblastoma cells the receptor tyrosine kinase c-Met is upregulated in response to bevacizumab and plays an important role in promoting invasion and tumor recurrence. These data support novel links between VEGF-A and hepatocyte growth factor and suggest that c-Met and its signaling effectors may be effective targets for anti-invasive therapies. Clin Cancer Res; 19(7); 1631–3. ©2013 AACR.
Phase I/II Study of the Rituximab-EPOCT Regimen in Combination with Granulocyte Colony-Stimulating Factor in Patients with Relapsed or Refractory Follicular Lymphoma Including Evaluation of Its Cardiotoxicity Using B-Type Natriuretic Peptide and Troponin T Levels
Authors: Nozomi Niitsu, Mika Khori, Miyuki Hayama, Koichi Kajiwara, Masaaki Higashihara, Jun-ichi Tamaru
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Standard treatment for relapsed or refractory follicular lymphoma has not been established. Doxorubicin is often given during the initial treatment. The dosage or drugs chosen for salvage therapy are limited by doxorubicin-induced cardiomyopathy. Experimental Design: The R-EPOCT (rituximab with etoposide, vincristine, pirarubicine, cyclophosphamide, and prednisone) regimen, in which less cardiotoxic pirarubicine is used instead of doxorubicin, with granulocyte colony-stimulating factor (G-CSF) was administered to 20 patients with relapsed or refractory follicular lymphoma. The safety (especially cardiotoxicity) and efficacy of this regimen were studied. As markers of cardiotoxicity, serum troponin T and plasma B-type natriuretic peptide (BNP) levels were measured. Results: Adverse reactions occurred in 14 of the 20 patients and mainly consisted of grade 3/4 hematologic toxicity. In the evaluation of cardiotoxicity, the BNP level was slightly elevated before the treatment in two patients and the BNP level did not significantly increase after R-EPOCT treatment. The troponin T level was undetectable before and after the treatment in all patients. The response rate was 100%, with complete remission in 16 patients (80%). G-CSF administration increased both Fc γ receptor type I expression on neutrophils and antibody-dependent cellular cytotoxicity activity. There were no significant differences in the levels of Fc γ receptor type I expression nor antibody-dependent cellular cytotoxicity activity after three or five cycles of the treatment. Conclusion: We conclude that the combination of R-EPOCT and G-CSF is well tolerated. This regimen was not cardiotoxic. We are planning a randomized trial to compare the efficacy between R-EPOCT and a combination of R-EPOCT with G-CSF.
Temporal patterns of occupational asbestos exposure and risk of pleural mesothelioma
Authors: Aude Lacourt, Karen Leffondré, Céline Gramond, Stéphane Ducamp, Patrick Rolland, Anabelle Gilg Soit Ilg, Marie Houot, Ellen Imbernon, Joëlle Févotte, Marcel Goldberg, Patrick Brochard
Journal: European Respiratory Journal (2011)

Asbestos is the primary cause of pleural mesothelioma (PM). The objective of this study was to elucidate the importance of different temporal patterns of occupational asbestos exposure on the risk of PM using case–control data in male subjects. Cases were selected from a French case–control study conducted in 1987–1993 and the French National Mesothelioma Surveillance Program in 1998–2006. Population controls were frequency matched to cases by year of birth. Occupational asbestos exposure was evaluated with a job–exposure matrix. The dose–response relationships were estimated using restricted cubic spline functions in logistic regression models. A total of 2,466 ever-asbestos-exposed males (1,041 cases and 1,425 controls) were used. After adjustment for intensity and total duration of occupational asbestos exposure, the risk of PM was lower for subjects first exposed after the age of 20 yrs and continued to increase until 30 yrs after cessation of exposure. The effect of total duration of exposure decreased when age at first exposure and time since last exposure increased. These results, based on a large population-based case–control study, underline the need to take into account the temporal pattern of exposure on risk assessment.
Failure to show mycoplasmas and cytopathogenic virus in rheumatoid arthritis.
Authors: P J Middleton, T C Highton
Journal: Annals of the Rheumatic Diseases (1975)

Synovial needle biopsies, joint aspirates, and joint tissue obtained at open operation from 41 cases of rheumatoid arthritis were inoculated onto PPLO media, L-form medium, and cell cultures for the isolation of mycoplasmas, L-form bacteria, and viruses. Medium suitable for the isolation of 'T' strain mycoplasmas was not employed. No mycoplasmas, L-form bacteria, or cytopathogenic viruses were shown. Similar specimens from nine patients diagnosed as having Reiter's disease were examined in a like manner and yielded only one Mycoplasma hominis type 1 isolate from a knee joint biopsy. It is concluded that known strains of mycoplasma and bacterial L-forms do not play a direct role in early and established cases of rheumatoid arthritis. Some of the cell cultures used in this study contained mycoplasma contaminants. Bacterial contaminants were also encountered in occasional batches of L-form medium.
Self-expandable stent versus balloon-expandable stent: a serial volumetric analysis by intravascular ultrasound
Authors: Y. Kobayashi, P.S. Teirstein, S.R. Bailey, C.L. Brown, L.G. Christie, R.V. Matthews, R.S. Schwartz, A.C. De Franco, C.E. Handen, P.G. Yock, P.J. Fitzgerald
Journal: Journal of the American College of Cardiology (1998)
Genetic Modulation of T Cell Receptor Gene Segment Usage during Somatic Recombination
Authors: Ferenc Livak, Douglas B. Burtrum, Lee Rowen, David G. Schatz, Howard T. Petrie
Journal: The Journal of Experimental Medicine (2000)

Lymphocyte antigen receptors are not encoded by germline genes, but rather are produced by combinatorial joining between clusters of gene segments in somatic cells. Within a given cluster, gene segment usage during recombination is thought to be largely random, with biased representation in mature T lymphocytes resulting from protein-mediated selection of a subset of the total repertoire. Here we show that T cell receptor Dβ and Jβ gene segment usage is not random, but is patterned at the time of recombination. The hierarchy of gene segment usage is independent of gene segment proximity, but rather is influenced by the ability of the flanking recombination signal sequences (RSS) to bind the recombinase and/or to form a paired synaptic complex. Importantly, the relative frequency of gene segment usage established during recombination is very similar to that found after protein-mediated selection, suggesting that in addition to targeting recombinase activity, the RSS may have evolved to bias the naive repertoire in favor of useful gene products.