tbuckley/cabot-search huggingface dataset:
Modulation of host antimicrobial peptide (beta-defensins 1 and 2) expression during gastritis
Authors: M Bajaj-Elliott
Journal: Gut (2002)

<b>Background:</b> β-Defensins are a newly identified family of antimicrobial peptides that are expressed by epithelia on mucosal surfaces where their production is augmented by infection or inflammation. <i>Helicobacter pylori</i> colonises the gastric epithelium causing persistent gastric inflammation leading to antral and corpus gastritis, and peptic ulcer disease. <b>Aims:</b> To evaluate the role of β-defensins in the innate immune response of the gastric epithelium to infection and inflammation, we have assessed mRNA expression and regulation of human β-defensins 1 and 2 (hBD1, hBD2) by <i>H pylori</i> and proinflammatory stimuli. We have also compared gene and peptide expression of these bactericidal agents in <i>H pylori</i> induced gastritis with that in normal gastric mucosa. <b>Methods:</b> Modulation of expression of hBD1 and hBD2 by various stimuli was studied in three (AGS, MKN7, MKN45) gastric epithelial cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR). Defensin mRNA expression was measured by semiquantitative RT-PCR in gastritis tissue and compared with controls. Peptide localisation was assessed by immunohistochemistry. <b>Results:</b> Cytotoxic <i>H pylori</i> and interleukin 1β (IL-1β) markedly upregulated expression of hBD2 in a dose and time dependent manner in both AGS and MKN7 cell lines. A modest increase in hBD1 expression was also noted during infection. Interestingly, induction of hBD1 gene expression by IL-1β was only observed in MKN7 cells. The magnitude of this response was delayed and reduced compared with hBD2 expression. In gastric biopsies, hBD2 was undetectable in normal gastric antrum but a marked increase was observed in <i>H pylori</i> positive gastritis compared with control tissue (p&lt;0.001). Constitutive expression of hBD1 was observed in normal gastric mucosa and there was a significant increase in gastritis (p&lt;0.05). Immunohistochemistry revealed a parallel increase in hBD1 and hBD2 peptide expression in gastritis tissue with positive staining confined to the surface epithelium of the gastric glands. <b>Conclusions:</b> Modulation of β-defensin expression by pathogenic and/or inflammatory stimuli and their cellular localisation places these antimicrobial peptides in the front line of innate host defence in the human stomach.
Secretory leucocyte proteinase inhibitor: inhibition of fibronectin degradation by neutrophil elastase
Authors: A Gervaix, R Thompson, JG Bieth, HP Nick, S Suter
Journal: European Respiratory Journal (1992)

Degradation of surface-bound fibronectin of the upper respiratory tract by human leucocyte elastase (HLE) was shown to favour colonization of these mucosal surfaces by Gram-negative bacteria. We investigated the degradation of fibronectin by purified HLE and by enzymes released from stimulated human polymorphonuclear leucocytes (PMNs), in the presence of recombinant secretory leucocyte proteinase inhibitor (rSLPI) and alpha 1-proteinase inhibitor (alpha 1-PI), the two main inhibitors of HLE within the airways. Our results show that HLE degraded fibronectin at concentrations as low as 0.2 nM. To inhibit the degradation of fibronectin by pure HLE in an experimental system in which the enzyme was premixed with inhibitor, a twofold molar excess of rSLPI and an equimolar concentration of alpha 1-PI were required. On the other hand, a fivefold molar excess of rSLPI was necessary to inhibit degradation of fibronectin by enzymes released from stimulated neutrophils. In order to estimate the role of oxidants generated by stimulated PMNs in the activation of the inhibitory capacity of rSLPI by stimulated PMNs, we preincubated PMNs with antioxidants such as superoxide dismutase, methionine, catalase or Na-azide prior to stimulation of the cells. Under these conditions, a threefold molar excess of rSLPI over released HLE was required to inhibit the degradation of fibronectin, raising the possibility that either exogenous or endogenous antioxidants in the lung could be important in improving the efficacy of this therapeutic antiprotease. We conclude that a molar excess of rSLPI to HLE is always necessary to inhibit fibronectin degradation by HLE, and that addition of antioxidants partly prevents the inactivation of rSLPI by oxidants released from stimulated PMNs.
p16 Expression As a Predictive Biomarker of Hypoxic Cell–Sensitizing Agents in Oropharyngeal Cancer
Authors: Christine H. Chung, David Raben
Journal: Journal of Clinical Oncology (2010)

tamoxifen-resistant breast carcinomas by gene expression profiling. J Clin Oncol 23:732-740, 2005 11. Yu J, Yu J, Cordero KE, et al: A transcriptional fingerprint of estrogen in human breast cancer predicts patient survival. Neoplasia 10:79-88, 2008 12. Oh DS, Troester MA, Usary J, et al: Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol 24:1656-1664, 2006 13. Loi S, Haibe-Kains B, Desmedt C, et al: Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen. BMC Genomics 9:239, 2008 14. McGuire WL: Breast cancer prognostic factors: Evaluation guidelines. J Natl Cancer Inst 83:154-155, 1991
Combined analysis reveals a core set of cycling genes
Authors: Yong Lu, Shaun Mahony, Panayiotis V Benos, Roni Rosenfeld, Itamar Simon, Linda L Breeden, Ziv Bar-Joseph
Journal: Genome biology (2007)

Abstract Background Global transcript levels throughout the cell cycle have been characterized using microarrays in several species. Early analysis of these experiments focused on individual species. More recently, a number of studies have concluded that a surprisingly small number of genes conserved in two or more species are periodically transcribed in these species. Combining and comparing data from multiple species is challenging because of noise in expression data, the different synchronization and scoring methods used, and the need to determine an accurate set of homologs. Results To solve these problems, we developed and applied a new algorithm to analyze expression data from multiple species simultaneously. Unlike previous studies, we find that more than 20% of cycling genes in budding yeast have cycling homologs in fission yeast and 5% to 7% of cycling genes in each of four species have cycling homologs in all other species. These conserved cycling genes display much stronger cell cycle characteristics in several complementary high throughput datasets. Essentiality analysis for yeast and human genes confirms these findings. Motif analysis indicates conservation in the corresponding regulatory mechanisms. Gene Ontology analysis and analysis of the genes in the conserved sets sheds light on the evolution of specific subfunctions within the cell cycle. Conclusion Our results indicate that the conservation in cyclic expression patterns is much greater than was previously thought. These genes are highly enriched for most cell cycle categories, and a large percentage of them are essential, supporting our claim that cross-species analysis can identify the core set of cycling genes.
Morphologic and angiographic features of coronary plaque rupture detected by intravascular ultrasound
Authors: Akiko Maehara, Gary S. Mintz, Anh B. Bui, Olga R. Walter, Marco T. Castagna, Daniel Canos, August D. Pichard, Lowell F. Satler, Ron Waksman, William O. Suddath, John R. Laird, Kenneth M. Kent, Neil J. Weissman
Journal: Journal of the American College of Cardiology (2002)
Surface lymphotoxin alpha/beta complex is required for the development of peripheral lymphoid organs.
Authors: P D Rennert, J L Browning, R Mebius, F Mackay, P S Hochman
Journal: The Journal of Experimental Medicine (1996)

For more than a decade, the biological roles and the apparent redundancy of the cytokines tumor necrosis factor (TNF) and lymphotoxin (LT) have been debated. LT alpha exists in its soluble form as a homotrimer, which like TNF only binds the TNF receptors, TNF-R55 or TNF-R75. The cell surface form of LT exists as a heteromer of LT alpha and LT beta subunits and this complex specifically binds the LT beta receptor (LT beta-R). To discriminate the functions of the LT and TNF systems, soluble LT beta-R-immunoglobulin (Ig) or TNF-R-Ig fusion proteins were introduced into embryonic circulation by injecting pregnant mice. Exposure to LT beta-R-Ig during gestation disrupted lymph node development and splenic architecture in the progeny indicating that both effects are mediated by the surface LT alpha/beta complex. These data are the first to identify a cell surface ligand involved in immune organ morphogenesis. Moreover, they unambiguously discriminate the functions of the various TNF/LT ligands, provide a unique model to study compartmentalization of immune responses and illustrate the generic utility of receptor-Ig fusion proteins for dissecting/ordering ontogenetic events in the absence of genetic modifications.
Phase II Study of Combination Therapy with S-1 and Irinotecan for Advanced Non–Small Cell Lung Cancer: West Japan Thoracic Oncology Group 3505
Authors: Isamu Okamoto, Takashi Nishimura, Masaki Miyazaki, Hiroshige Yoshioka, Akihito Kubo, Koji Takeda, Noriyuki Ebi, Shunichi Sugawara, Nobuyuki Katakami, Masahiro Fukuoka, Kazuhiko Nakagawa
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the efficacy and toxicity of combination therapy with the oral fluoropyrimidine formulation S-1 and irinotecan for patients with advanced NSCLC. Experimental Design: Chemotherapy-naive patients with advanced NSCLC were treated with i.v. irinotecan (150 mg/m2) on day 1 and with oral S-1 (80 mg/m2) on days 1 to 14 every 3 weeks. Results: Fifty-six patients (median age, 63 years; range, 40-74 years) received a total of 286 treatment cycles (median, 5; range, 1-15). No complete responses and 16 partial responses were observed, giving an overall response rate of 28.6% [95% confidence interval (95% CI), 17.3-42.2%]. Twenty-four patients (42.9%) had stable disease and 12 patients (21.4%) had progressive disease as the best response. The overall disease control rate (complete response + partial response + stable disease) was thus 71.4% (95% CI, 57.8-82.7%). Median progression-free survival was 4.9 months (95% CI, 4.0-6.4 months), whereas median overall survival was 15 months. Hematologic toxicities of grade 3 or 4 included neutropenia (25%), thrombocytopenia (3.6%), and anemia (3.6%), with febrile neutropenia being observed in four patients (7.1%). The most common nonhematologic toxicities of grade 3 or 4 included anorexia (14.3%), fatigue (8.9%), and diarrhea (8.9%). There were no deaths attributed to treatment. Conclusions: The combination of S-1 and irinotecan is a potential alternative option with a favorable toxicity profile for the treatment of advanced NSCLC. This nonplatinum regimen warrants further evaluation in randomized trials.
Evolution of the core and pan-genome of Streptococcus: positive selection, recombination, and genome composition
Authors: Tristan Lefébure, Michael J Stanhope
Journal: Genome biology (2007)

The genus Streptococcus is one of the most diverse and important human and agricultural pathogens. This study employs comparative evolutionary analyses of 26 Streptococcus genomes to yield an improved understanding of the relative roles of recombination and positive selection in pathogen adaptation to their hosts.
Vitamin D receptor gene expression in mammalian kidney.
Authors: L Liu, M Ng, A M Iacopino, S T Dunn, M R Hughes, J E Bourdeau
Journal: Journal of the American Society of Nephrology (1994)

The vitamin D-receptor protein and its mRNA were localized in microscope sections of paraffin-embedded mammalian kidneys by means of immunocytochemistry and in situ hybridization, respectively. A monoclonal antibody against chicken intestinal vitamin D receptor immunostained the nucleus and cytoplasm of cells within the distal convoluted tubule, connecting segment, and initial cortical collecting duct of both rats and pigs. Although fainter, immunostaining also was present over proximal tubular cells. (35S)UTP-labeled cRNA probes were detected over both the proximal and distal portions of the mouse nephron, but silver grain densities were 5.8-fold greater over the latter. In conclusion, localization of both the vitamin D-receptor protein and its mRNA in both the proximal and distal nephron of adult mammals suggests that the gene for this protein is expressed in cells at both of these sites. The intensity of immunostaining and the density of cRNA-associated silver grains suggest that vitamin D-receptor gene expression is greatest in the distal nephron.
After My Father's Stroke
Authors: G. Jensen
Journal: JAMA (2003)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Breath condensate ammonium is lower in children with chronic asthma
Authors: G. MacGregor, S. Ellis, J. Andrews, M. Imrie, A. Innes, A. P. Greening, S. Cunningham
Journal: European Respiratory Journal (2005)

Exhaled breath condensate pH and ammonium reflect asthmatic status and acute exacerbations in adults. The aim of this study was to assess whether pH and ammonium could reflect asthma and its severity in children. The current study comprised two parts: 1) a cross-section of 74 children with asthma (median age 10.5 yrs) compared with 47 healthy controls (median age 10 yrs); and 2) longitudinal assessment of eight children (mean age 8.5 yrs) admitted with asthma exacerbation. Condensate pH and ammonium were compared with clinical observations. In the cross-sectional part of the study, lower per cent forced expiratory volume in one second was associated with more symptoms and treatment. There was no significant difference between median pH in children with stable asthma (6.05) compared with controls (5.90). Ammonium was significantly lower in children with asthma (median 258 µM) compared with controls (median 428 µM). No association was found between ammonium or pH and lung function or symptom-free days. In the longitudinal study, significant improvements in oxygen saturation and respiratory rate with treatment of an acute exacerbation were not reflected by changes in pH or ammonium. In conclusion, pH does not appear to reflect disease or severity in children with asthma. Ammonium was significantly lower in children with asthma when compared with controls.
Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine Administered According to 4 Different Primary Immunization Schedules in Infants
Authors: Judith Spijkerman, Reinier H. Veenhoven, Alienke J. Wijmenga-Monsuur, Karin E. M. Elberse, Pieter G. M. van Gageldonk, Mirjam J. Knol, Hester E. de Melker, Elisabeth A. M. Sanders, Leo M. Schouls, Guy A. M. Berbers
Journal: JAMA (2013)

Immunization schedules with pneumococcal conjugate vaccine (PCV) differ among countries regarding the number of doses, age at vaccinations, and interval between doses.To assess the optimal primary vaccination schedule by comparing immunogenicity of 13-valent PCV (PCV13) in 4 different immunization schedules.An open-label, parallel-group, randomized clinical trial of healthy term infants in a general community in The Netherlands conducted between June 30, 2010, and January 25, 2011, with 99% follow-up until age 12 months.Infants (N = 400) were randomly assigned (1:1:1:1) to receive PCV13 either at ages 2, 4, and 6 months (2-4-6); at ages 3 and 5 months (3-5); at ages 2, 3, and 4 months (2-3-4); or at ages 2 and 4 months (2-4), with a booster dose at age 11.5 months.Primary outcome measure was antibody geometric mean concentrations (GMCs) against PCV13-included serotypes 1 month after the booster dose measured by multiplex immunoassay. Secondary outcomes included GMCs measured 1 month after the primary series, at 8 months of age, and before the booster.The primary outcome, GMCs at 1 month after the booster dose, was not significantly different between schedules for 70 of 78 comparisons. The 2-4-6 schedule was superior to the 2-3-4 schedule for serotypes 18C (10.2 µg/mL [95% CI, 8.2-12.7] vs 6.5 µg/mL [95% CI, 5.4-7.8]) and 23F (10.9 µg/mL [95% CI, 9.0-13.3] vs 7.3 µg/mL [95% CI, 5.8-9.2]) and superior to the 2-4 schedule for serotypes 6B (8.5 µg/mL [95% CI, 7.1-10.2] vs 5.1 µg/mL [95% CI 3.8-6.7]), 18C (6.6 µg/mL [95% CI, 5.7-7.7]), and 23F (7.2 µg/mL [95% CI, 5.9-8.8]). For serotype 1, the 3-5 schedule (11.7 µg/mL [95% CI, 9.6-14.3]) was superior to the other schedules. Geometric mean concentrations for all 13 serotypes ranged between 1.6 and 19.9 µg/mL. Secondary outcomes demonstrated differences 1 month after the primary series. The 2-4-6 schedule was superior compared with the 3-5, 2-3-4, and 2-4 schedules for 3, 9, and 11 serotypes, respectively. Differences between schedules persisted until the booster dose.The use of 4 different PCV13 immunization schedules in healthy term infants resulted in no statistically significant differences in antibody levels after the booster dose for almost all serotypes. The choice of PCV schedule will require a balance between the need for early protection and maintaining protection between the primary series and the booster.trialregister.nl Identifier: NTR2316.
Apical lung herniation
Authors: H. Ranu, M. Jackson
Journal: Thorax (2011)

A 50-year-old man was referred to us complaining of a swelling in his neck while coughing. He had a 1-year history of a dry cough. He was an ex-smoker with a 10 pack-year history. Examination of his chest at rest was normal, without any cervical lymphadenopathy or signs of superior vena cava obstruction (figure 1A). Examination while coughing revealed a visible swelling on the right side of the neck (figure …
Statins, Rho GTPases and KLF2: new mechanistic insight into liver fibrosis and portal hypertension
Authors: Jonel Trebicka, Robert Schierwagen
Journal: Gut (2015)

Statins, standard of care drugs used in metabolic syndrome and cardiovascular diseases, seem to be safe for chronic liver disease.1 ,2 Beyond their cholesterol-lowering effect by inhibition of 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase), statins exert multiple pleiotropic effects.3 These pleiotropic effects make statins cheap and also well-investigated drugs in terms of tolerability and safety. Therefore, statins offer possibilities not only to test new hypotheses, and reveal novel pathomechanisms and targets, as shown by Marrone et al in this issue,4 but also for therapeutic approaches. Indeed, use of statins might attenuate liver fibrosis in patients with chronic hepatitis C infection;5 it reduced hepatic vascular resistance and portal pressure in patients with cirrhosis.6 ,7 The Barcelona group has performed pioneer clinical and experimental work for the use of statins in portal hypertension. A recent Spanish multicentre study, headed by the same group and presented in European Association for the Study of the Liver (EASL) 2014, showed that statins …
LARGE-SCALE GENOMIC APPROACHES TO BRAIN DEVELOPMENT AND CIRCUITRY
Authors: Mary E. Hatten, Nathaniel Heintz
Journal: Annual Review of Neuroscience (2005)

Over the past two decades, molecular genetic studies have enabled a common conceptual framework for the development and basic function of the nervous system. These studies, and the pioneering efforts of mouse geneticists and neuroscientists to identify and clone genes for spontaneous mouse mutants, have provided a paradigm for understanding complex processes of the vertebrate brain. Gene cloning for human brain malformations and degenerative disorders identified other important central nervous system (CNS) genes. However, because many debilitating human disorders are genetically complex, phenotypic screens are difficult to design. This difficulty has led to large-scale, genomic approaches to discover genes that are uniquely expressed in brain circuits and regions that control complex behaviors. In this review, we summarize current phenotype- and genotype-driven approaches to discover novel CNS-expressed genes, as well as current approaches to carry out large-scale, gene-expression screens in the CNS.
Reduced Body Size and Decreased Intestinal Tumor Rates in HDAC2-Mutant Mice
Authors: Stephan Zimmermann, Franz Kiefer, Michela Prudenziati, Carmen Spiller, Jens Hansen, Thomas Floss, Wolfgang Wurst, Saverio Minucci, Martin Göttlicher
Journal: Cancer Research (2007)

Abstract Histone deacetylases (HDAC) reverse the acetylation of histone and nonhistone proteins and thereby modulate chromatin structure and function of nonhistone proteins. Many tumor cell lines and experimental tumors respond to HDAC inhibition. To assess the role of an individual HDAC isoenzyme in physiology and tumor development, HDAC2-mutant mice were generated from a gene trap embryonic stem cell clone. These mice express a catalytically inactive fusion protein of the NH2-terminal part of HDAC2 and β-galactosidase, which fails to integrate into corepressor complexes with mSin3B. They are the first class 1 HDAC mutant mice that are viable although they are ∼25% smaller than their littermates. Cell number and thickness of intestinal mucosa are reduced. Mutant embryonic fibroblasts fail to respond to insulin-like growth factor I (IGF) by the IGF-I–induced increase in cell number observed in wild-type cells. These data suggest a novel link between HDACs and IGF-I–dependent responses. Crossing of HDAC2-mutant with tumor-prone APCmin mice revealed tumor rates that are lower in HDAC2-deficient mice by 10% to 100% depending on segment of the gut and sex of the mice. These mice provide evidence that the key functions of HDAC2, although not essential for survival of the organism, play a rate-limiting role for tumor development in vivo. [Cancer Res 2007;67(19):9047–54]