tbuckley/cabot-search huggingface dataset:
Mitogenic Effect of Angiotensin II on Rat Carotid Arteries and Type II or III Mesenteric Microvessels but Not Type I Mesenteric Microvessels Is Mediated by Endogenous Basic Fibroblast Growth Factor
Authors: E. J. Su, D. M. Lombardi, J. Wiener, M. J. A. P. Daemen, M. A. Reidy, S. M. Schwartz
Journal: Circulation Research (1998)

Abstract —In this study, anti–basic fibroblast growth factor (anti-bFGF) antibody was used to determine whether the mitogenic effect of angiotensin II in vivo could be blocked by neutralizing bFGF in the vessel wall. Animals, divided into six experimental groups, were given (1) angiotensin II, (2) angiotensin II+anti-bFGF antibody, (3) angiotensin II+normal goat IgG (ngIgG), (4) anti-bFGF antibody, (5) ngIgG, and (6) Ringer’s solution. Angiotensin II at 435 ng · kg −1 · min −1 was infused into rats continuously for 1 week to induce smooth muscle cell replication, and anti-bFGF antibody or ngIgG was injected intravenously 4 times over the 1-week period at a dose of 60 mg/injection. Bromodeoxyuridine (30 mg/mL) was also continuously infused during the 1-week period. The left carotid artery of all animals was balloon-injured on day 4 of the treatment, and all groups were killed for study on day 7. The results showed that angiotensin II significantly stimulated smooth muscle replication in the balloon-injured carotid artery, intact carotid artery, and three branch levels of the mesenteric vascular tree. Anti-bFGF was able to block the mitogenic effect of angiotensin II in larger vessels but not the smallest (type I) microvessels of the mesenteric arterial tree. This differential response may be attributable to the nature of the lesions in type I vessels versus larger vessels: the type I vascular lesion has a large component of proliferating macrophages, whereas the larger vessels show less injury, few macrophages, and varying levels of smooth muscle replication. Our data suggest that the vessel wall remodeling in the angiotensin II–treated larger vessels involves DNA replication that is dependent on the presence of bFGF.
Outcome after Treatment of High-Risk Papillary and Non-Hurthle-Cell Follicular Thyroid Carcinoma
Authors: T Taylor, B Specker, J Robbins, M Sperling, M Ho, K Ain, S T Bigos, J Brierley, D Cooper, B Haugen, I Hay, V Hertzberg, I Klein, H Klein, P Ladenson, R Nishiyama, D Ross, S Sherman, H R Maxon
Journal: Annals of Internal Medicine (1998)

Treatment of differentiated thyroid cancer has been studied for many years, but the benefits of extensive initial thyroid surgery and the addition of radioiodine therapy or external radiation therapy remain controversial.To determine the relations among extent of surgery, radioiodine therapy, and external radiation therapy in the treatment of high-risk papillary and non-Hürthle-cell follicular thyroid carcinoma.Analysis of data from a multicenter study.14 institutions in the United States and Canada participating in the National Thyroid Cancer Treatment Cooperative Study Registry.385 patients with high-risk thyroid cancer (303 with papillary carcinoma and 82 with follicular carcinoma).Death, disease progression, and disease-free survival.Total or near-total thyroidectomy was done in 85.3% of patients with papillary carcinoma and 71.3% of patients with follicular cancer. Overall surgical complication rate was 14.3%. Total or near-total thyroidectomy improved overall survival (risk ratio [RR], 0.37 [95% CI, 0.18 to 0.75]) but not cancer-specific mortality, progression, or disease-free survival in patients with papillary cancer. No effect of extent of surgery was seen in patients with follicular thyroid cancer. Postoperative iodine-131 was given to 85.4% of patients with papillary cancer and 79.3% of patients with follicular cancer. In patients with papillary cancer, radioiodine therapy was associated with improvement in cancer-specific mortality (RR, 0.30 [CI, 0.09 to 0.93 by multivariate analysis only]) and progression (RR, 0.30 [CI, 0.13 to 0.72]). When tall-cell variants were excluded, the effect on outcome was not significant. After radioiodine therapy, patients with follicular thyroid cancer had improvement in overall mortality (RR, 0.17 [CI, 0.06 to 0.47]), cancer-specific mortality (RR, 0.12 [CI, 0.04 to 0.42]), progression (RR, 0.21 [CI, 0.08 to 0.56]), and disease-free survival (RR, 0.29 [CI, 0.08 to 1.01]). External radiation therapy to the neck was given to 18.5% of patients and was not associated with improved survival, lack of progression, or disease-free survival.This study supports improvement in overall and cancer-specific mortality among patients with papillary and follicular thyroid cancer after postoperative iodine-131 therapy. Radioiodine therapy was also associated with improvement in progression in patients with papillary cancer and improvement in progression and disease-free survival in patients with follicular carcinoma.
Validation and comparison of SCAP as a predictive score for identifying low-risk patients in community-acquired pneumonia
Authors: Pedro P España, Alberto Capelastegui, José M Quintana, Amaia Bilbao, Rosa Diez, Silvia Pascual, Cristóbal Esteban, Rafael Zalacaín, Rosario Menendez, Antoni Torres
Journal: Journal of Infection (2009)
Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck
Authors: James A. Bonner, Paul M. Harari, Jordi Giralt, Nozar Azarnia, Dong M. Shin, Roger B. Cohen, Christopher U. Jones, Ranjan Sur, David Raben, Jacek Jassem, Roger Ove, Merrill S. Kies, Jose Baselga, Hagop Youssoufian, Nadia Amellal, Eric K. Rowinsky, K. Kian Ang
Journal: New England Journal of Medicine (2006)

We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck.
Glomus Tumors in Neurofibromatosis Type 1: Genetic, Functional, and Clinical Evidence of a Novel Association
Authors: Hilde Brems, Caroline Park, Ophélia Maertens, Alexander Pemov, Ludwine Messiaen, Meena Upadhyaya, Kathleen Claes, Eline Beert, Kristel Peeters, Victor Mautner, Jennifer L. Sloan, Lawrence Yao, Chyi-Chia Richard Lee, Raf Sciot, Luc De Smet, Eric Legius, Douglas R. Stewart
Journal: Cancer Research (2009)

Neurofibromatosis type 1 (NF1) is a common disorder that arises secondary to mutations in the tumor suppressor gene NF1. Glomus tumors are small, benign but painful tumors that originate from the glomus body, a thermoregulatory shunt concentrated in the fingers and toes. We report 11 individuals with NF1 who harbored 20 glomus tumors of the fingers and 1 in the toe; 5 individuals had multiple glomus tumors. We hypothesized that biallelic inactivation of NF1 underlies the pathogenesis of these tumors. In 12 NF1-associated glomus tumors, we used cell culture and laser capture microdissection to isolate DNA. We also analyzed two sporadic (not NF1-associated) glomus tumors. Genetic analysis showed germ line and somatic NF1 mutations in seven tumors. RAS mitogen-activated protein kinase hyperactivation was observed in cultured NF1(-/-) glomus cells, reflecting a lack of inhibition of the pathway by functional neurofibromin, the protein product of NF1. No abnormalities in NF1 or RAS mitogen-activated protein kinase activation were found in sporadic glomus tumors. By comparative genomic hybridization, we observed amplification of the 3'-end of CRTAC1 and a deletion of the 5'-end of WASF1 in two NF1-associated glomus tumors. For the first time, we show that loss of neurofibromin function is crucial in the pathogenesis of glomus tumors in NF1. Glomus tumors of the fingers or toes should be considered as part of the tumor spectrum of NF1.
Temperature-sensitive tyrosinase associated with peripheral pigmentation in oculocutaneous albinism.
Authors: R A King, D Townsend, W Oetting, C G Summers, D P Olds, J G White, R A Spritz
Journal: Journal of Clinical Investigation (1991)

Several types of autosomal recessive oculocutaneous albinism (OCA) are associated with abnormal tyrosinase function and a generalized reduction in or absence of cutaneous and eye melanin. Each is thought to result from a different mutant allele at the tyrosinase locus, with the mutation producing an enzyme with little or no activity in all involved tissues. In this paper, we report a new type of OCA that results from a tyrosinase allele producing a temperature-sensitive enzyme. The proband had white hair in the warmer areas (scalp and axilla) and progressively darker hair in the cooler areas (extremities) of her body. Melanocyte and melanosome architecture were normal. Quantitative hairbulb tyrosinase (dopa oxidase) assay demonstrated a loss of activity above 35-37 degrees C. Plasma pheomelanin and urine eumelanin intermediates were reduced and correlated with hair melanin content. This is the first temperature-sensitive tyrosinase mutation to be reported in humans and is analogous to the Siamese mutation in the cat and the Himalayan mutation in the mouse.
Effects of Retinoids on the TGF-β System and Extracellular Matrix in Experimental Glomerulonephritis
Authors: CHRISTIAN MORATH, CLAUDIUS DECHOW, INGO LEHRKE, VOLKER HAXSEN, RÜDIGER WALDHERR, JÜRGEN FLOEGE, EBERHARD RITZ, JÜRGEN WAGNER
Journal: Journal of the American Society of Nephrology (2001)

Transforming growth factor—β1 (TGF-β1) overexpression plays a key role in the glomerular accumulation of extracellular matrix proteins in renal disease. Retinoids have previously been shown to significantly limit glomerular damage in rat experimental glomerulonephritis. Therefore, the effects of all-trans retinoic acid and isotretinoin on the components of the TGF-β system and extracellular matrix proteins in anti-Thy1.1-nephritis (Thy-GN) were investigated. Vehicle-injected control rats were compared with rats treated with daily subcutaneous injections of 10 mg/kg body wt all-trans retinoic acid or 40 mg/kg body wt isotretinoin (n = 9 per group) either with a pretreatment (day -2 through 8) or posttreatment protocol (day +3 through 8), i.e., starting before or after induction of Thy-GN, respectively. Urinary TGF-β1 excretion was 60% lower in all-trans retinoic acid-treated animals with Thy-GN (P < 0.025). The increase of cortical TGF-β1 gene expression in Thy-GN rats was significantly attenuated with all-trans retinoic acid and even more with isotretinoin treatment as compared with untreated animals (P < 0.025). Cortical expression of TGF receptor II, but not receptor I gene expression, was significantly lower in animals treated with all-trans retinoic acid or isotretinoin (P < 0.05). In all-trans retinoic acid—treated animals with Thy-GN, the increase of glomerular TGF-β1 protein (P < 0.008) and TGF-β1 (P < 0.025) and TGF receptor II mRNA (P < 0.015) was significantly less. Immunohistochemistry revealed less glomerular staining for TGF-β1 and TGF receptor II in the presence of all-trans retinoic acid. TGF-β1 immunostaining was not restricted to monocytes and macrophages, as indicated by double-staining. Glomerular staining for collagen IV and collagen III was less in animals treated with isotretinoin (P < 0.02 for both) in contrast to all-trans retinoic acid, whereas fibronectin remained unchanged. It was concluded that the beneficial effects of retinoids on glomerular damage are presumably due to a marked reduction in renal TGF-β1 and TGF receptor II expression.
Long term infliximab treatment for severe psoriatic arthritis: evidence of sustained clinical and radiographic response
Authors: F Rinaldi, G Provenzano, A Termini, M Spinello, F La Seta
Journal: Annals of the Rheumatic Diseases (2005)

This case illustrates the usefulness of a therapeutic trial of colchicine monitored objectively by frequent acute phase protein measurements in patients with undiagnosed periodic fever syndromes.It also raises the possibility that a low threshold for analysing the FMF gene might disclose a wider spectrum of associated disease.
Comprehensive self management and routine monitoring in chronic obstructive pulmonary disease patients in general practice: randomised controlled trial
Authors: E. W. M. A. Bischoff, R. Akkermans, J. Bourbeau, C. van Weel, J. H. Vercoulen, T. R. J. Schermer
Journal: BMJ (2012)

To assess the long term effects of two different modes of disease management (comprehensive self management and routine monitoring) on quality of life (primary objective), frequency and patients' management of exacerbations, and self efficacy (secondary objectives) in patients with chronic obstructive pulmonary disease (COPD) in general practice.24 month, multicentre, investigator blinded, three arm, pragmatic, randomised controlled trial.15 general practices in the eastern part of the Netherlands.Patients with COPD confirmed by spirometry and treated in general practice. Patients with very severe COPD or treated by a respiratory physician were excluded.A comprehensive self management programme as an adjunct to usual care, consisting of four tailored sessions with ongoing telephone support by a practice nurse; routine monitoring as an adjunct to usual care, consisting of 2-4 structured consultations a year with a practice nurse; or usual care alone (contacts with the general practitioner at the patients' own initiative).The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory questionnaire total score. Secondary outcomes were chronic respiratory questionnaire domain scores, frequency and patients' management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system, and self efficacy measured with the COPD self-efficacy scale.165 patients were allocated to self management (n=55), routine monitoring (n=55), or usual care alone (n=55). At 24 months, adjusted treatment differences between the three groups in mean chronic respiratory questionnaire total score were not significant. Secondary outcomes did not differ, except for exacerbation management. Compared with usual care, more exacerbations in the self management group were managed with bronchodilators (odds ratio 2.81, 95% confidence interval 1.16 to 6.82) and with prednisolone, antibiotics, or both (3.98, 1.10 to 15.58).Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice. Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group.Clinical trials NCT00128765.
Genetic Variants Contributing to Daunorubicin-Induced Cytotoxicity
Authors: R. Stephanie Huang, Shiwei Duan, Emily O. Kistner, Wasim K. Bleibel, Shannon M. Delaney, Donna L. Fackenthal, Soma Das, M. Eileen Dolan
Journal: Cancer Research (2008)

Abstract Identifying heritable genetic variants responsible for chemotherapeutic toxicities has been challenging due in part to its multigenic nature. To date, there is a paucity of data on genetic variants associated with patients experiencing severe myelosuppression or cardiac toxicity following treatment with daunorubicin. We present a genome-wide model using International HapMap cell lines that integrate genotype and gene expression to identify genetic variants that contribute to daunorubicin-induced cytotoxicity. A cell growth inhibition assay was used to measure variations in the cytotoxicity of daunorubicin. Gene expression was determined using the Affymetrix GeneChip Human Exon 1.0ST Array. Using sequential analysis, we evaluated the associations between genotype and cytotoxicity, those significant genotypes with gene expression and correlated gene expression of the identified candidates with cytotoxicity. A total of 26, 9, and 18 genetic variants were identified to contribute to daunorubicin-induced cytotoxicity through their effect on 16, 9, and 36 gene expressions in the combined, Centre d' Etude du Polymorphisme Humain (CEPH), and Yoruban populations, respectively. Using 50 non-HapMap CEPH cell lines, single nucleotide polymorphisms generated through our model predicted 29% of the overall variation in daunorubicin sensitivity and the expression of CYP1B1 was significantly correlated with sensitivity to daunorubicin. In the CEPH validation set, rs120525235 and rs3750518 were significant predictors of transformed daunorubicin IC50 (P = 0.005 and P = 0.0008, respectively), and rs1551315 trends toward significance (P = 0.089). This unbiased method can be used to elucidate genetic variants contributing to a wide range of cellular phenotypes. [Cancer Res 2008;68(9):3161–8]
Do Lung Remodeling, Repair, and Regeneration Recapitulate Respiratory Ontogeny?
Authors: DAVID WARBURTON, DENISE TEFFT, ARNAUD MAILLEUX, SAVERIO BELLUSCI, JEAN-PAUL THIERY, JINGSONG ZHAO, SUE BUCKLEY, WEI SHI, BARBARA DRISCOLL
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Herein we posit that modeling of the lungs during morphogenesis, repair, and regeneration is tightly coordinated by conserved stimulatory and inhibitory signaling mechanisms, including specific transcriptional factors, cytokines, peptide growth factors, proteases, and matrix elements. This evolutionary-developmental (evo-devo) functional conservation has been extended to morphogenesis of the respiratory tracheae in Drosophila. Fifty or more genes direct fruit fly tracheal organogenesis. Among them, hedgehog, patched, smoothened, cubitus interruptus, branchless, breathless, sprouty, decapentaplegic, and mad are functionally conserved between flies, mice, and humans. For example, fibroblast growth factor (FGF) signaling is essential, not only for fly trachea and mouse bronchial branching morphogenesis, but also for postnatal modeling and repair of alveoli. Likewise, sprouty family genes act as inducible negative regulators of FGF signaling, which in part may determine interbranch length during bronchial development. Alveolar epithelial survival, migration, and proliferation during remodeling after hyperoxic injury also require FGF signaling. In addition, FGF signaling appears to regulate a small (< 5%) population of putative alveolar stem/ progenitor cells that express telomerase and are relatively resistant to hyperoxic apoptosis. We speculate that genes in evo-devo functionally conserved signaling pathways such as FGF-FGF receptor-Sprouty may provide novel therapeutic targets to augment lung repair and induce lung regeneration.
Cellular Retinoic Acid–Binding Protein II Is a Direct Transcriptional Target of MycN in Neuroblastoma
Authors: Anu Gupta, Bryan R.G. Williams, Samir M. Hanash, Jawhar Rawwas
Journal: Cancer Research (2006)

Abstract Neuroblastoma is a heterogeneous disease in which 22% of tumors show MycN oncogene amplification and are associated with poor clinical outcome. MycN is a transcription factor that regulates the expression of a number of proteins that affect the clinical behavior of neuroblastoma. We report here that cellular retinoic acid–binding protein II (CRABP-II) is a novel MycN target, expressed at significantly higher levels in primary neuroblastoma tumors with mycN oncogene amplification as compared with non–MycN-amplified tumors. Moreover, regulated induction and repression of MycN in a neuroblastoma-derived cell line resulted in temporal and proportionate expression of CRABP-II. CRABP-II is expressed in several cancers, but its role in tumorigenesis has not been elucidated. We show that MycN binds to the promoter of CRABP-II and induces CRABP-II transcription directly. In addition, CRABP-II-transfected neuroblastoma cell lines show an increase in MycN protein levels resulting in increased cell motility. Gene expression profiling of CRABP-II-expressing cell lines uncovered increased expression of the HuB (Hel N1) gene. Hu proteins have been implicated in regulating the stability of MycN mRNA and other mRNAs by binding to their 3′ untranslated regions. We did not, however, observe any change in MycN mRNA stability or protein half-life in response to CRABP-II expression. In contrast, de novo MycN protein synthesis was increased in CRABP-II-expressing neuroblastoma cells, thereby suggesting an autoregulatory loop that might exacerbate the effects of MycN gene amplification and affect the clinical outcome. Our findings also suggest that CRABP-II may be a potential therapeutic target for neuroblastoma. (Cancer Res 2006; 66(16): 8100-8)
Coalescent-Based Analysis Distinguishes between Allo- and Autopolyploid Origin in Shepherd's Purse (Capsella bursa-pastoris)
Authors: K. R. St. Onge, J. P. Foxe, J. Li, H. Li, K. Holm, P. Corcoran, T. Slotte, M. Lascoux, S. I. Wright
Journal: Molecular Biology and Evolution (2012)

Polyploidization plays an important role in plant speciation. The most recent estimates report that up to 15% of angiosperm speciation events and 31% in ferns are accompanied by changes in ploidy level. Polyploids can arise either through autopolyploidy, when the sets of chromosomes originate from a single species, or through allopolyploidy, when they originate from different species. In this study, we used two different coalescent-based methods to determine the date and mode of the polyploidization event that led to the tetraploid cosmopolitan weed, Capsella bursa-pastoris. We sampled 78 C. bursa-pastoris accessions, and 53 and 43 accessions from the only two other members of this genus, C. grandiflora and C. rubella, respectively, and sequenced these accessions at 14 unlinked nuclear loci with locus-specific primers in order to be able to distinguish the two homeologues in the tetraploid. A large fraction of fixed differences between homeologous genes in C. bursa-pastoris are segregating as polymorphisms in C. grandiflora, consistent with an autopolyploid origin followed by disomic inheritance. To test this, we first estimated the demographic parameters of an isolation-with-migration model in a pairwise fashion between C. grandiflora and both genomes of C. bursa-pastoris and used these parameters in coalescent simulations to test the mode of origin of C. bursa-pastoris. Second, we used Approximate Bayesian Computation to compare an allopolyploid and an autopolyploid model. Both analyses led to the conclusion that C. bursa-pastoris originated less than 1 Ma by doubling of the C. grandiflora genome.
Christmas curios from Brazil
Authors: P D Marsden
Journal: BMJ (1989)

clerk. And days passed and weeks; the eldest girl went to work in the postman's house, where she was content, and the blacksmith's wife unwillingly took over the new baby. The other six, Chomin, Shanti, Martinacho, Joshe, Maru, and Gaspar, ran barefoot about the highway, begging for alms. One morning the gravedigger came to the village with a cart, put the six little ones in it, took the baby in his arms, buying a feeding bottle for it as he passed the chemist's, and took them all to his cottage in the cemetery. Humbug, said the mayor. Idiot, murmured the chemist. The vicar delicately lifted his eyes, averting them from such misfortune. ''He'll abandon them, forecast the clerk. Pachi has not abandoned them and is helping them along and as he has many mouths to fill has given up his brandy but is now filling the cemetery with vegetables to a most regrettable degree. And as there is now a market in the village Pachi arranges with a friend of his, who lives near the cemetery, to sell his cabbages and artichokes in the market square. The cabbages of Pachi's friend, which come from the cemetery, are known for their flavour and are very popular in the village market. What the buyers do not know is that they are cheerfully obtaining sustenance from the bodies of their ancestors.