tbuckley/cabot-search huggingface dataset:
Regulation of phospholipase D and primary granule secretion by P2-purinergic- and chemotactic peptide-receptor agonists is induced during granulocytic differentiation of HL-60 cells.
Authors: M S Xie, L S Jacobs, G R Dubyak
Journal: Journal of Clinical Investigation (1991)

We have compared the abilities of extracellular ATP (acting via P2-purinergic receptors) and formylated peptides (FMLP) to stimulate both phospholipase D (PLD)-based signal transduction and primary granule (azurophilic) secretion in HL-60 cells induced to differentiate along the granulocytic pathway. In undifferentiated HL-60 cells, neither ATP nor FMLP elicited significant PLD activation or increased secretion despite the previously documented ability of ATP to stimulate large increases in polyphosphoinositide hydrolysis and Ca2+ mobilization. Conversely, within 1 d after induction of granulocytic differentiation by dibutyryl cAMP, both ATP and FMLP induced large increases in azurophilic secretion and corresponding increases in PLD activity. ATP-activated PLD activity was near-maximal within 1 d after dibutyryl cAMP treatment, while the FMLP-induced activity increased continuously over 4 d, with a maximal level twice that stimulated by ATP. Additional experiments characterized the activation of PLD by receptor-independent pathways at different stages of differentiation; these included studies of phorbol ester action in intact cells and GTP gamma S action in electropermeabilized cells. An apparent role for guanine nucleotide-binding regulatory proteins in PLD regulation was also indicated by the significant reduction in FMLP- and ATP-stimulated PLD activity observed in cells pretreated with pertussis toxin. At all stages of differentiation, there was good correlation between the relative efficacies of ATP versus FMLP in stimulating both secretion and PLD activity. These data indicate: (a) that the receptor-regulated phospholipase D signaling pathway is induced during differentiation of myeloid progenitor cells; and (b) that differential activation of this signaling system by various Ca(2+)-mobilizing receptor agonists may underlie the differential regulation of secretion and other phagocyte functions by such agents.
Dual mutations in the AML1 and FLT3 genes are associated with leukemogenesis in acute myeloblastic leukemia of the M0 subtype
Authors: N Matsuno, M Osato, N Yamashita, M Yanagida, T Nanri, T Fukushima, T Motoji, S Kusumoto, M Towatari, R Suzuki, T Naoe, K Nishii, K Shigesada, R Ohno, H Mitsuya, Y Ito, N Asou
Journal: Leukemia (2003)
CD8 is required during positive selection of CD4-/CD8+ T cells.
Authors: J C Zúñiga-Pflücker, L A Jones, D L Longo, A M Kruisbeek
Journal: The Journal of Experimental Medicine (1990)

Interactions between self-MHC molecules and T cells are necessary for the proper development of mature T cells, in part due to an absolute requirement for self-MHC-TCR interactions. Recently, we showed that CD4-mediated interactions also participate in shaping the T cell repertoire during thymic maturation. We now examine the possible role of the CD8 molecule during in vivo T cell development. Our results demonstrate that perinatal thymi treated with intact anti-CD8 mAb fail to generate CD8 single-positive T cells, while the generation of the other main phenotypes remains unchanged. Most importantly, the use of F(ab')2 anti-CD8 mAb fragments gave identical results, i.e., lack of generation of CD4-/CD8+ cells, with no effect on the generation of CD4+/CD8+. Furthermore, selective blocking of one CD8 allele with F(ab')2 mAbs in F1 mice expressing both CD8 alleles did not interfere with the development of CD4-/CD8+ cells, demonstrating that the absence of CD8+ T cells in homozygous mice is not due to depletion, but rather is caused by a lack of positive selection. This is most likely attributable to a deficient CD8-MHC class I interaction. Our findings strongly advocate that CD8 molecules are vital to the selection process that leads to the development of mature single-positive CD8 T cells.
Child abuse and paediatrics
Authors: Timothy J David
Journal: Journal of the Royal Society of Medicine (2005)

There have been many success stories in paediatrics, but finding a good way to deal with child abuse is not yet one of them; indeed, for this reason paediatricians in the UK are under fierce attack. From your superior knowledge of fifty years hence, dear reader in 2055, you may wonder how the specialty came to be in such a predicament. However, you should bear in mind that, as I write, hardly more than forty years have passed since child abuse entered the medical consciousness.
Commentaries on the end of year editorial on the definition of ischaemia in last December's issue
Authors: L. C Becker
Journal: Cardiovascular Research (1995)

Commentaries on the end of year editorial on the definition of ischaemia in last December's issue Get access Lewis C Becker, Dr Lewis C Becker, Dr Johns Hopkins University School of Medicine, Baltimore, Maryland, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 29, Issue 2, February 1995, Pages 288–289, https://doi.org/10.1016/S0008-6363(95)90010-1 Published: 01 February 1995
Burden of colonoscopy compared to non-cathartic CT-colonography in a colorectal cancer screening programme: randomised controlled trial
Authors: Thomas R de Wijkerslooth, Margriet C de Haan, Esther M Stoop, Patrick M Bossuyt, Maarten Thomeer, Marie-Louise Essink-Bot, Monique E van Leerdam, Paul Fockens, Ernst J Kuipers, Jaap Stoker, Evelien Dekker
Journal: Gut (2011)

<h3>Objective</h3> CT-colonography has been suggested to be less burdensome for primary colorectal cancer (CRC) screening than colonoscopy. To compare the expected and perceived burden of both in a randomised trial. <h3>Design</h3> 8844 Dutch citizens aged 50–74 years were randomly invited for CRC screening with colonoscopy (n=5924) or CT-colonography (n=2920). Colonoscopy was performed after full colon lavage, or CT-colonography after limited bowel preparation (non-cathartic). All invitees were asked to complete the expected burden questionnaire before the procedure. All participants were invited to complete the perceived burden questionnaire 14 days later. Mean scores were calculated on 5-point scales. <h3>Results</h3> Expected burden: 2111 (36%) colonoscopy and 1199 (41%) CT-colonography invitees completed the expected burden questionnaire. Colonoscopy invitees expected the bowel preparation and screening procedure to be more burdensome than CT-colonography invitees: mean scores 3.0±1.1 vs 2.3±0.9 (p&lt;0.001) and 3.1±1.1 vs 2.2±0.9 (p&lt;0.001). Perceived burden: 1009/1276 (79%) colonoscopy and 801/982 (82%) CT-colonography participants completed the perceived burden questionnaire. The full screening procedure was reported as more burdensome in CT-colonography than in colonoscopy: 1.8±0.9 vs 2.0±0.9 (p&lt;0.001). Drinking the bowel preparation resulted in a higher burden score in colonoscopy (3.0±1.3 vs 1.7±1.0, p&lt;0.001) while related bowel movements were scored more burdensome in CT-colonography (2.0±1.0 vs 2.2±1.1, p&lt;0.001). Most participants would probably or definitely take part in a next screening round: 96% for colonoscopy and 93% for CT-colonography (p=0.99). <h3>Conclusion</h3> In a CRC screening programme, colonoscopy invitees expected the screening procedure and bowel preparation to be more burdensome than CT-colonography invitees. In participants, CT-colonography was scored as more burdensome than colonoscopy. Intended participation in a next screening round was comparable.
Impaired Processing of DNA Photoproducts and Ultraviolet Hypermutability With Loss of p16INK4a or p19ARF
Authors: Papri Sarkar-Agrawal, Irene Vergilis, Norman E Sharpless, Ronald A DePinho, Thomas M Rünger
Journal: JNCI Journal of the National Cancer Institute (2004)

Reduced DNA repair has been linked to an increased risk of cutaneous malignant melanoma, but insights into the molecular mechanisms of that link are scarce. The INK4a/ARF (CDKN2a) locus, which codes for the p16(INK4a) and p19ARF proteins, is often mutated in sporadic and familial malignant melanoma, but it has not been directly associated with reduced DNA repair. We transfected unirradiated mouse fibroblast cells with UV-treated DNA to measure DNA repair in normal, p16INK4a mutant, p19ARF mutant, or double mutant mouse host cells. Loss of either p16(INK4a) or p19ARF reduced the ability of the cells to process UV-induced DNA damage, independent of cell cycle effects incurred by the loss. These results may further explain why INK4a/ARF mutations predispose to malignant melanoma, a UV-induced tumor.
Climatic suitability of Aedes albopictus in Europe referring to climate change projections: comparison of mechanistic and correlative niche modelling approaches
Authors: D Fischer, S M Thomas, M Neteler, N B Tjaden, C Beierkuhnlein
Journal: Eurosurveillance (2014)

The Asian tiger mosquito, Aedes albopictus, is capable of transmitting a broad range of viruses to humans. Since its introduction at the end of the 20th century, it has become well established in large parts of southern Europe. As future expansion as a result of climate change can be expected, determining the current and projected future climatic suitability of this invasive mosquito in Europe is of interest. Several studies have tried to detect the potential habitats for this species, but differing data sources and modelling approaches must be considered when interpreting the findings. Here, various modelling methodologies are compared with special emphasis on model set-up and study design. Basic approaches and model algorithms for the projection of spatio-temporal trends within the 21st century differ substantially. Applied methods range from mechanistic models (e.g. overlay of climatic constraints based on geographic information systems or rather process-based approaches) to correlative niche models. We conclude that spatial characteristics such as introduction gateways and dispersal pathways need to be considered. Laboratory experiments addressing the climatic constraints of the mosquito are required for improved modelling results. However, the main source of uncertainty remains the insufficient knowledge about the species' ability to adapt to novel environments.
A Role for Wnt Signaling Genes in the Pathogenesis of Impaired Lung Function in Asthma
Authors: Sunita Sharma, Kelan Tantisira, Vincent Carey, Amy J. Murphy, Jessica Lasky-Su, Juan C. Celedón, Ross Lazarus, Barbara Klanderman, Angela Rogers, Manuel Soto-Quirós, Lydiana Avila, Thomas Mariani, Roger Gaedigk, Stephen Leeder, John Torday, David Warburton, Benjamin Raby, Scott T. Weiss
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Animal models demonstrate that aberrant gene expression in utero can result in abnormal pulmonary phenotypes.Objectives: We sought to identify genes that are differentially expressed during in utero airway development and test the hypothesis that variants in these genes influence lung function in patients with asthma.Methods: Stage 1 (Gene Expression): Differential gene expression analysis across the pseudoglandular (n = 27) and canalicular (n = 9) stages of human lung development was performed using regularized t tests with multiple comparison adjustments. Stage 2 (Genetic Association): Genetic association analyses of lung function (FEV1, FVC, and FEV1/FVC) for variants in five differentially expressed genes were conducted in 403 parent-child trios from the Childhood Asthma Management Program (CAMP). Associations were replicated in 583 parent-child trios from the Genetics of Asthma in Costa Rica study.Measurements and Main Results: Of the 1,776 differentially expressed genes between the pseudoglandular (gestational age: 7–16 wk) and the canalicular (gestational age: 17–26 wk) stages, we selected 5 genes in the Wnt pathway for association testing. Thirteen single nucleotide polymorphisms in three genes demonstrated association with lung function in CAMP (P < 0.05), and associations for two of these genes were replicated in the Costa Ricans: Wnt1-inducible signaling pathway protein 1 with FEV1 (combined P = 0.0005) and FVC (combined P = 0.0004), and Wnt inhibitory factor 1 with FVC (combined P = 0.003) and FEV1/FVC (combined P = 0.003).Conclusions: Wnt signaling genes are associated with impaired lung function in two childhood asthma cohorts. Furthermore, gene expression profiling of human fetal lung development can be used to identify genes implicated in the pathogenesis of lung function impairment in individuals with asthma.
The relationship between neck circumference, radiographic pharyngeal anatomy, and the obstructive sleep apnoea syndrome
Authors: RJ Davies, None Stradling
Journal: European Respiratory Journal (1990)

We have studied the predictive importance of neck circumference, obesity, and several radiographic pharyngeal dimensions for obstructive sleep apnoea (OSA), in 66 patients. OSA was quantified as the mean hourly number of greater than 4% dips in arterial oxygen saturation during sleep. Neck circumference (correlation coefficient (r) = 0.63, 95% confidence interval (C.I.) 0.46-0.76), obesity index (r = 0.54, 95% C.I. 0.39-0.69), hyoid position (r = 0.40, 95% C.I. 0.17-0.59), soft palate length (r = 0.31, 95% C.I. 0.08-0.51), and hard palate-to-spine angle (r = 0.29, 95% C.I. 0.04-0.49), correlated significantly with saturation dips in single regression analysis. In stepwise multiple linear regression analysis (saturation dip rate as the dependent variable), only neck size and retroglossal space were significant independent correlates (total r2 = 0.42, 95% C.I. 0.22-0.61, p less than 0.0001). We conclude that the relationships between general obesity, hyoid position, soft palate length, and OSA are probably secondary to variation in neck circumference.
p53-Responsive miR-194 Inhibits Thrombospondin-1 and Promotes Angiogenesis in Colon Cancers
Authors: Prema Sundaram, Stacy Hultine, Lauren M. Smith, Michael Dews, Jamie L. Fox, Dauren Biyashev, Janell M. Schelter, Qihong Huang, Michele A. Cleary, Olga V. Volpert, Andrei Thomas-Tikhonenko
Journal: Cancer Research (2011)

Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by the THBS1 gene, whose promoter is activated by p53. In advanced colorectal cancers (CRC), its expression is sustained or even slightly increased despite frequent loss of p53. Here, we determined that in HCT116 CRC cells, p53 activates the THBS1 primary transcript, but fails to boost THBS1 mRNA or protein levels, implying posttranscriptional regulation by microRNAs (miRNA). In a global miRNA gain-of-function screen done in the Dicer-deficient HCT116 variant, several miRNAs negatively regulated THBS1 mRNA and protein levels, one of them being miR-194. Notably, in agreement with published data, p53 upregulated miR-194 expression in THBS1 retrovirus-transduced HCT116 cells, leading to decreased TSP-1 levels. This negative effect was mediated by a single miR-194 complementary site in the THBS1 3'-untranslated region, and its elimination resulted in TSP-1 reactivation, impaired angiogenesis in Matrigel plugs, and reduced growth of HCT116 xenografts. Conversely, transient overexpression of miR-194 in HCT116/THBS1 cells boosted Matrigel angiogenesis, and its stable overexpression in Ras-induced murine colon carcinomas increased microvascular densities and vessel sizes. Although the overall contribution of miR-194 to neoplastic growth is context dependent, p53-induced activation of this GI tract-specific miRNA during ischemia could promote angiogenesis and facilitate tissue repair.
Respiratory viral infections in community-acquired pneumonia and exacerbation of COPD: One year survey at a Japanese university hospital
Authors: Daisuke Kurai, Takeshi Saraya, Haruyuki Ishii, Hiroyuki Tukagoshi, Hirokazu Kimura, Hajime Takizawa
Journal: European Respiratory Journal (2014)

Aims: Respiratory viral infections (RVI) are common and may be serious. Thus, we investigate the prevalence and characteristics of RVI in community acquired pneumonia (CAP) and exacerbation of COPD. Methods: A prospective observational cohort study was conducted in Kyorin University Hospital under the institutional approval, Tokyo, Japan from August 2012 to August 2013.Patients who were admitted on CAP and exacerbation of COPD were included and their respiratory samples and clinical data were obtained after informed consent, and analyzed using a PCR method to identify common respiratory viruses . Results: Fifty-five subjects, which consisted of CAP (n=45, male 29: female 16, mean age 72) and COPD (n=10, male7: female 3, mean age 73) were enrolled. Proportions of viral detection in CAP and exacerbation of COPD were 13% (6/45) and 50% (5/10), respectively. Three cases in CAP were co-infected with bacteria, while co-infection with bacteria was not detected in COPD. Identified viruses in CAP were human rhinovirus: HRV (n=2), human metapneumovirus: HMPV (n=3) and parainfluenza virus (n=1). Detected viruses in COPD exacerbation were respiratory syncytial virus: RSV (n=2) influenza virus (n=1) HMPV (n=1) and HRV (n=1). Two patients died within 30 days among patients with CAP, although any viral were not detected in these patients. On the contrary, three patients died in COPD exacerbation, two patients died of RVI. Conclusion: RVI were noted in about 13 % and 50 % of hospitalized CAP and exacerbation of COPD patients. RVI in hospitalized patients with exacerbation of COPD were a major cause and lead to fatal course.
Additional Reasons for Not Viewing Continuous Sedation as Preferable Alternative for Physician-Assisted Suicide
Authors: Suzanne van de Vathorst, Maartje Schermer
Journal: The American Journal of Bioethics (2011)

"Additional Reasons for Not Viewing Continuous Sedation as Preferable Alternative for Physician-Assisted Suicide." The American Journal of Bioethics, 11(6), pp. 43–44 Acknowledgments This research was supported by a grant from the Netherlands Organization for Health Research and Development (ZonMw). The authors thank all the members of the KOPPEL study for our lively discussions.
Screening for Chronic Kidney Disease
Authors: William M. McClellan, Sylvia P. B. Ramirez, Claudine Jurkovitz
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. End-stage renal disease is epidemic in the United States. As a measure to control this epidemic, it has been recommended that individuals who are at risk for CKD be tested for undetected kidney disease during routine health care encounters. There are generally accepted criteria against which screening recommendations for CKD control and prevention programs should be judged. If detection strategies are to be adopted for the screening of kidney disease, then CKD must represent a significant public health problem, be characterized by a clear natural history with a detectable asymptomatic period, outcomes should be improved by early treatment, and acceptable screening tests should be available. Health systems must provide adequate and appropriate follow-up medical care for individuals with newly detected CKD. Finally, the cost-effectiveness of screening needs to be demonstrated and the effectiveness of screening as a means of achieving reductions in CKD should be proven in randomized trials. E-mail [email protected]
The etiology of liver damage imparts cytokines transforming growth factor β1 or interleukin-13 as driving forces in fibrogenesis
Authors: Hong-Lei Weng, Yan Liu, Jia-Lin Chen, Tong Huang, Li-Jun Xu, Patricio Godoy, Jun-Hua Hu, Cheng Zhou, Felix Stickel, Alexander Marx, Rainer M. Bohle, Vincent Zimmer, Frank Lammert, Sebastian Mueller, Michelle Gigou, Didier Samuel, Peter R. Mertens, Manfred V. Singer, Helmut K. Seitz, Steven Dooley
Journal: Hepatology (2009)

It is unknown whether transforming growth factor beta1 (TGF-beta1) signaling uniformly participates in fibrogenic chronic liver diseases, irrespective of the underlying origin, or if other cytokines such as interleukin (IL)-13 share in fibrogenesis (e.g., due to regulatory effects on type I pro-collagen expression). TGF-beta1 signaling events were scored in 396 liver tissue samples from patients with diverse chronic liver diseases, including hepatitis B virus (HBV), hepatitis C virus (HCV), Schistosoma japonicum infection, and steatosis/steatohepatitis. Phospho-Smad2 staining correlated significantly with fibrotic stage in patients with HBV infection (n = 112, P < 0.001) and steatosis/steatohepatitis (n = 120, P < 0.01), but not in patients with HCV infection (n = 77, P > 0.05). In tissue with HBx protein expression, phospho-Smad2 was detectable, suggesting a functional link between viral protein expression and TGF-beta1 signaling. For IL-13, immunostaining correlated with fibrotic stage in patients with HCV infection and steatosis/steatohepatitis. IL-13 protein was more abundant in liver tissue lysates from three HCV patients compared with controls, as were IL-13 serum levels in 68 patients with chronic HCV infection compared with 20 healthy volunteers (72.87 +/- 26.38 versus 45.41 +/- 3.73, P < 0.001). Immunohistochemistry results suggest that IL-13-mediated liver fibrogenesis may take place in the absence of phospho-signal transducer and activator of transcription protein 6 signaling. In a subgroup of patients with advanced liver fibrosis (stage > or =3), neither TGF-beta nor IL-13 signaling was detectable.Depending on the cause of liver damage, a predominance of TGF-beta or IL-13 signaling is found. TGF-beta1 predominance is detected in HBV-related liver fibrogenesis and IL-13 predominance in chronic HCV infection. In some instances, the underlying fibrogenic mediator remains enigmatic.
High street eye tests.
Authors: A R Rosenthal
Journal: BMJ (1990)

hygiene, foot care, vision, and dentition.'4In the elderlyas in other age groups-there is little place for screening for asymptomatic disease. 15An exception might be the identification and careful treatment of patients up to the age of 80. 16If screening programmes are to have any impact it is important that identification of problems is followed by action.General practitioners, for example, will have to have facilities for evaluating or referring patients who are identified as having visual or hearing defects and give attention to using effective instruments for differentiating dementia from depression in patients with psychiatric abnormalities. 17Moreover, screening will probably further highlight deficiencies in the local provision of geriatric, psychiatric, social work, and ancillary services.Though doubts remain about the value ofrecent legislation, it should at least focus attention on the needs ofthe elderly and stimulate debate on how best to improve their quality of care.
Monocytes find a new place to dwell in the niche of heartbreak hotel
Authors: Bart Lambrecht, Martin Guilliams
Journal: The Journal of Experimental Medicine (2014)

![Figure][1] 

Insight from Bart Lambrecht (left) and Martin Guilliams (right)

Lambrecht Photo courtesy of [www.vib.be][2]



Monocytes and macrophages belong to the mononuclear phagocyte system (MPS). The concept of the MPS is based on the idea that circulating monocytes represent the
A Critical Analysis of the Long-Term Impact of Radical Prostatectomy on Cancer Control and Function Outcomes
Authors: Stephen A. Boorjian, James A. Eastham, Markus Graefen, Bertrand Guillonneau, R. Jeffrey Karnes, Judd W. Moul, Edward M. Schaeffer, Christian Stief, Kevin C. Zorn
Journal: European Urology (2011)
634 Assessment of biliary fibrosis by transient elastography in PBC and PSC patients
Authors: C. Corpechot, A. El Naggar, A. Poujol-Robert, M. Ziol, D. Wendum, O. Chazouillères, V. de Ledinghen, D. Dhumeaux, P. Marcellin, M. Beaugrand, R. Poupon
Journal: Journal of Hepatology (2006)