tbuckley/cabot-search huggingface dataset:
Rac1 and RhoA differentially regulate angiotensinogen gene expression in stretched cardiac fibroblasts
Authors: Suresh K. Verma, Hind Lal, Honey B. Golden, Fnu Gerilechaogetu, Manuela Smith, Rakeshwar S. Guleria, Donald M. Foster, Guangrong Lu, David E. Dostal
Journal: Cardiovascular Research (2010)

Angiotensin II (Ang II) stimulates cardiac remodelling and fibrosis in the mechanically overloaded myocardium. Although Rho GTPases regulate several cellular processes, including myocardial remodelling, involvement in mediating mechanical stretch-induced regulation of angiotensinogen (Ao), the precursor to Ang II, remains to be determined. We, therefore, examined the role and associated signalling mechanisms of Rho GTPases (Rac1 and RhoA) in regulation of Ao gene expression in a stretch model of neonatal rat cardiac fibroblasts (CFs).CFs were plated on deformable stretch membranes. Equiaxial mechanical stretch caused significant activation of both Rac1 and RhoA within 2-5 min. Rac1 activity returned to control levels after 4 h, whereas RhoA remained at a high level of activity until the end of the stretch period (24 h). Mechanical stretch initially caused a moderate decrease in Ao gene expression, but was significantly increased at 8-24 h. RhoA had a major role in mediating both the stretch-induced inhibition of Ao at 4 h and the subsequent upregulation of Ao expression at 24 h. β₁ integrin receptor blockade by Tac β₁ expression impaired acute (2 and 15 min) stretch-induced Rac1 activation, but increased RhoA activity. Molecular experiments revealed that Ao gene expression was inhibited by Rac1 through both JNK-dependent and independent mechanisms, and stimulated by RhoA through a p38-dependent mechanism.These results indicate that stretch-induced activation of Rac1 and RhoA differentially regulates Ao gene expression by modulating p38 and JNK activation.
Objectively Measured Physical Activity and the Subsequent Risk of Incident Dysglycemia
Authors: Anne-Louise Ponsonby, Cong Sun, Obioha C. Ukoumunne, Angela Pezic, Alison Venn, Jonathan E. Shaw, David W. Dunstan, Elizabeth L.M. Barr, Steven N. Blair, Jenny Cochrane, Paul Z. Zimmet, Terence Dwyer
Journal: Diabetes Care (2011)

To investigate pedometer-measured physical activity (PA) in 2000 and change in PA over 5 years with subsequent risk of dysglycemia by 2005.This prospective cohort study in Tasmania, Australia, analyzed 458 adults with normal glucose tolerance and a mean (SD) age of 49.7 (12.1) years in 2000. Variables assessed in 2000 and 2005 included PA, by pedometer and questionnaire, nutrient intake, and other lifestyle factors. Incident dysglycemia was defined as the development of impaired fasting glucose or impaired glucose tolerance revealed by oral glucose tolerance testing in 2005, without type 2 diabetes.Incident dysglycemia developed in 26 participants during the 5-year period. Higher daily steps in 2000 were independently associated with a lower 5-year risk of incident dysglycemia (adjusted odds ratio [AOR] 0.87 [95% CI 0.77-0.97] per 1,000-step increment). Higher daily steps in 2005, after controlling for baseline steps in 2000 (thus reflecting change in steps over 5 years), were not associated with incident dysglycemia (AOR 1.02 [0.92-1.14]). Higher daily steps in 2000 were also associated with lower fasting blood glucose, but not 2-h plasma glucose by 2005. Further adjustment for BMI or waist circumference did not remove these associations.Among community-dwelling adults, a higher rate of daily steps is associated with a reduced risk of incident dysglycemia. This effect appears to be not fully mediated through reduced adiposity.
Single nucleotide polymorphisms in the gene encoding the major histocompatibility complex class II transactivator (CIITA) in systemic lupus erythematosus
Authors: K Koizumi
Journal: Annals of the Rheumatic Diseases (2005)

The major histocompatibility complex (MHC) class II transactivator (CIITA) is a master switch of antigen presentation and activates expression of the MHC II gene. Insufficient up regulation of MHC class II molecules is reported to be one of the major immunological mechanisms in systemic lupus erythematosus (SLE).To examine the association between single nucleotide polymorphisms (SNPs) in the human CIITA gene (MHC2TA) and SLE.Promoters and coding regions of MHC2TA were evaluated for polymorphisms in 100 patients with SLE and 100 healthy donors. Eight oligonucleotide primer sets that covered the coding region and each promoter region were used for genomic analysis of SNPs.Allele frequencies of previously reported SNPs did not differ between healthy donors and patients with SLE. Additionally, a new polymorphism in an intronic region at nt 485 (A-->A/G) was identified, which is close to the polymorphism at nt 474 that has been associated with one of the disease causing CIITA cDNA mutations in bare lymphocyte syndrome. This SNP was found in 11% of patients with SLE and in 3% of healthy donors, suggesting it may have a role in the pathogenesis of SLE.A newly identified polymorphism in an intronic region at nt 485 (A-->A/G) may have an important role in the pathogenesis of SLE.
World's first double leg transplantation is carried out in Spain
Authors: M. de Lago
Journal: BMJ (2011)

The first double leg transplantation in the world has been performed in Spain on a patient in his early 20s whose legs were amputated above his knees after a car crash.

The transplantation, overseen by the surgeon Pedro Cavadas in La Fe Hospital, Valencia, was approved by the Spanish National Transplant Organisation in May 2010 but was only done overnight on 10 July after the right donor was found. The operation involved more than 50 medical staff and took around 10 hours.

The patient, whose …
LMP-associated proteolytic activities and TAP-dependent peptide transport for class 1 MHC molecules are suppressed in cell lines transformed by the highly oncogenic adenovirus 12.
Authors: R Rotem-Yehudar, M Groettrup, A Soza, P M Kloetzel, R Ehrlich
Journal: The Journal of Experimental Medicine (1996)

Expression of class I major histocompatibility complex antigens on the surface of cells transformed by adenovirus 12 (Ad12) is generally very low, and correlates with the in vivo oncogenicity of this virus. In primary embryonal fibroblasts (H-2b) that express transgenic swine class I antigen (PD1), Ad12-mediated transformation results in inhibition in transport of newly synthesized class I molecules, as well as significant reduction in transporter associated with antigen presentation (TAP) gene expression. In this report we show that reexpression of TAP molecules either by stable transfection of mouse TAP genes or by infection with recombinant vaccinia viruses expressing human TAP genes, only partially reconstitutes the expression and transport of the class I molecules. Further analysis of Ad12-transformed cells revealed that the expression of both LMP2 and LMP7, but not of other proteasome complex components, was downregulated, resulting in altered proteolytic activities of the 20S proteasomes. Reconstitution of both TAP and LMP expression resulted in complete restoration of PD1 cell surface expression and enhanced expression of the endogenous H-2D(b) molecules encoded by recombinant vaccinia viruses, in reconstituted Ad12-transformed cells, efficient transport of H-2 class I molecules could only be achieved by treatment of the cells with gamma-interferon. These data suggest that an additional factor(s) that is interferon-regulated plays a role in the biosynthetic pathway of the class I complex, and that its function is deficient in this cell system. Thus, Ad12 viral transformation appears to suppress the expression of multiple genes that are important for antigen processing and presentation, which allows such transformed cells to escape immune surveillance. This coordinate downregulation of immune response genes must likely occur through their use of common regulatory elements.
Pseudomonas exit site infections in continuous ambulatory peritoneal dialysis patients.
Authors: H R Kazmi, F D Raffone, A S Kliger, F O Finkelstein
Journal: Journal of the American Society of Nephrology (1992)

The purpose of this study is to examine the natural history of Pseudomonas aeruginosa exit site infections in continuous ambulatory peritoneal dialysis (CAPD) patients treated with oral ciprofloxacin and local exit site care. A retrospective view was undertaken of 18 episodes of P. aeruginosa exit site infections developing in 17 patients maintained on CAPD during 1989 and 1990. Standardized therapy for the exit site infection consisted of oral ciprofloxacin (500 mg twice daily) and local exit site care with antiseptic agents. Fifteen (83%) of 18 of the pseudomonas exit site infections resolved with therapy. Three episodes (17%) required catheter removal to successfully eradicate the infection. Four of the 15 patients whose exit site infections resolved developed P. aeruginosa peritonitis 2 to 9 months after the clinical resolution of the exit site infection. The majority of pseudomonas exit site infections in CAPD patients can be successfully treated with oral ciprofloxacin and local care. Approximately 17% of the patients in this study required catheter removal to successfully eradicate the infection and an additional 22% of the patients developed pseudomonas peritonitis several months after the resolution of the exit site infection.
Representation of similarities – a psychometric but not an explanatory concept for categorization
Authors: Martin Jüttner
Journal: Behavioral and Brain Sciences (1998)

The representation of similarities is a viable concept for a cognitive extension of visual psychophysics to the recognition of shapes, bringing issues such as similarity and categorization back into that field. However, as a framework it appears too general to place constraints on a particular process model for categorization. In particular, a preference for Chorus-like schemes with respect to structure-oriented approaches is unwarranted.
Long-term results from a phase II study of single agent paclitaxel (Taxol®) in previously platinum treated patients with advanced ovarian cancer: The Nordic experience
Authors: C. Tropé, Th. Hogberg, J. Kaern, K. Bertelsen, E. Bjorkholm, K. Boman, A. Himmelmann, G. Horvath, A. Jacobsen, T. Kuoppola, J. Vartianen, B. Lund, M. Onsrud, U. Puistola, T. Salmi, M. Scheistroen, R. Sandvei, E. Simonsen, B. Sorbe, B. Tholander, R. Westberg
Journal: Annals of Oncology (1998)
Management of pregnant women infected with Ebola virus in a treatment centre in Guinea, June 2014
Authors: F M Baggi, A Taybi, A Kurth, M Van Herp, A Di Caro, R Wölfel, S Günther, T Decroo, H Declerck, S Jonckheere
Journal: Eurosurveillance (2014)

Binary file ES_Abstracts_Final_ECDC.txt matches
Reduced expression of AMPK-β1 during tumor progression enhances the oncogenic capacity of advanced ovarian cancer
Authors: Cuilan Li, Vincent WS Liu, Pui Man Chiu, Kwok-Ming Yao, Hextan YS Ngan, David W Chan
Journal: Molecular Cancer (2014)

AMP-activated protein kinase (AMPK) is a key energy sensor that is involved in regulating cell metabolism. Our previous study revealed that the subunits of the heterotimeric AMPK enzyme are diversely expressed during ovarian cancer progression. However, the impact of the variable expression of these AMPK subunits in ovarian cancer oncogenesis remains obscure. Here, we provide evidence to show that reduced expression of the AMPK-β1 subunit during tumor progression is associated with the increased oncogenic capacity of advanced ovarian cancer cells. Immunohistochemical analysis revealed that AMPK-β1 levels were reduced in advanced-stage (P = 0.008), high-grade (P = 0.013) and metastatic ovarian cancers (P = 0.008). Intriguingly, down-regulation of AMPK-β1 was progressively reduced from tumor stages 1 to 3 of ovarian cancer. Functionally, enforced expression of AMPK-β1 inhibited ovarian-cancer-cell proliferation, anchorage-independent cell growth, cell migration and invasion. Conversely, depletion of AMPK-β1 by siRNA enhanced the oncogenic capacities of ovarian cancer cells, suggesting that the loss of AMPK-β1 favors the aggressiveness of ovarian cancer. Mechanistically, enforced expression of AMPK-β1 increased AMPK activity, which, in turn, induced cell-cycle arrest via inhibition of AKT/ERK signaling activity as well as impaired cell migration/invasion through the suppression of JNK signaling in ovarian cancer cells. Taken together, these findings suggest that the reduced expression of AMPK-β1 confers lower AMPK activity, which enhances the oncogenic capacity of advanced-stage ovarian cancer.
Noninvasive Imaging of Angiogenesis With a <sup>99m</sup> Tc-Labeled Peptide Targeted at α <sub>v</sub> β <sub>3</sub> Integrin After Murine Hindlimb Ischemia
Authors: Jing Hua, Lawrence W. Dobrucki, Mehran M. Sadeghi, Jiasheng Zhang, Brian N. Bourke, Patti Cavaliere, James Song, Conroy Chow, Neda Jahanshad, Niels van Royen, Ivo Buschmann, Joseph A. Madri, Marivi Mendizabal, Albert J. Sinusas
Journal: Circulation (2005)

Background— Noninvasive imaging strategies play a critical role in assessment of the efficacy of angiogenesis therapies. The α v β 3 integrin is activated in angiogenic vessels and represents a potential target for noninvasive imaging of angiogenesis. Methods and Results— We evaluated a 99m Tc-labeled peptide (NC100692) targeted at α v β 3 integrin for imaging in an established murine model of angiogenesis induced by hindlimb ischemia. Control mice (n=9) or mice with surgical right femoral artery occlusion (n=29) were injected with NC100692 (1.5±0.2 mCi IV) at different times after femoral occlusion (1, 3, 7, and 14 days) for in vivo pinhole planar gamma camera imaging. Tissue from hindlimb proximal and distal to occlusion was excised for gamma well counting and for immunostaining. On in vivo pinhole images, increased focal NC100692 activity was seen distal to the occlusion at days 3 and 7. This increase in relative NC100692 activity was confirmed by gamma well counting. Lectin staining confirmed increased angiogenesis in the ischemic hindlimb at these time points. A fluorescent analogue of NC100692 was used to confirm specificity and localization of the targeted tracer in cultured endothelial cells. In addition, endothelial cell specificity was confirmed on tissue sections with the use of dual immunofluorescent staining of endothelium and the fluorescent analogue targeted at the α v β 3 integrin. Conclusions— A 99m Tc-labeled peptide (NC100692) targeted at α v β 3 integrin selectively localized to endothelial cells in regions of increased angiogenesis and could be used for noninvasive serial “hot spot” imaging of angiogenesis. This targeted radiotracer imaging approach is a major advance in tracking therapeutic myocardial angiogenesis and has an important clinical potential.
Terminal Illness and Risk of Suicide
Authors: P. Anthony Chapdelaine
Journal: JAMA (1993)

To the Editor.  —The report by Cote et al1showing that men with acquired immunodeficiency syndrome (AIDS) have a 7.4-fold higher suicide rate than men in the general population was carefully done, with underreporting and overreporting properly addressed. The authors note that a better comparison for computing the relative risk of suicide in persons with AIDS is by using men in similar risk groups (homosexuals and drug users) rather than the general population. Although there are no accurate suicide rates for homosexual men, suicide attempts and completions are higher than for the general population, especially for male homosexual youth.2Likewise, drug abuse is a recognized risk factor for suicide and a potential confounder. Nonetheless, the authors' risk estimate is reasonable.  The parallel between Huntington's disease and AIDS is clear, the former having a genetic and the latter an acquired defect, both leading to physical and neurological/mental disability and
Effect of weight reduction in obese patients diagnosed with knee osteoarthritis: a systematic review and meta-analysis
Authors: R. Christensen, E. M. Bartels, A. Astrup, H. Bliddal
Journal: Annals of the Rheumatic Diseases (2006)

This review aims to assess by meta-analysis of randomised controlled trials (RCTs) changes in pain and function when overweight patients with knee osteoarthritis (OA) achieve a weight loss. Systematic searches were performed and reference lists from the retrieved trials were searched. RCTs were enclosed in the systematic review if they explicitly stated diagnosis of knee OA and reported a weight change as the only difference in intervention from the control group. Outcome Measures for Arthritis Clinical Trials III outcome variables were considered for analysis. Effect size (ES) was calculated using RevMan, and meta-regression analyses were performed using weighted estimates from the random effects analyses. Among 35 potential trials identified, four RCTs including five intervention/control groups met our inclusion criteria and provided data from 454 patients. Pooled ES for pain and physical disability were 0.20 (95% CI 0 to 0.39) and 0.23 (0.04 to 0.42) at a weight reduction of 6.1 kg (4.7 to 7.6 kg). Meta-regression analysis showed that disability could be significantly improved when weight was reduced over 5.1%, or at the rate of >0.24% reduction per week. Clinical efficacy on pain reduction was present, although not predictable after weight loss. Meta-regression analysis indicated that physical disability of patients with knee OA and overweight diminished after a moderate weight reduction regime. The analysis supported that a weight loss of >5% should be achieved within a 20-week period--that is, 0.25% per week.
Isochromosome of Chromosome 12: Clinically Useful Marker for Male Germ Cell Tumors
Authors: J.G. Bosl, E. Dmitrovsky, V. E. Reuter, F. Samaniego, E. Rodriguez, N. L. Geller, R. S. K. Chaganti
Journal: JNCI Journal of the National Cancer Institute (1989)

Twenty-nine tumor specimens were obtained from 24 males with germ cell tumors. All primary sites and histologies were represented. An isochromosome of the short arm of chromosome 12 [i (12p)] was found in 20 specimens obtained from 16 patients, a 46,XY normal karyotype was present in seven specimens, and one specimen was a cytogenetic failure. The i(12p) was found in tumors from all primary sites and in all histologies, including a choriocarcinoma. The presence of three or more additional copies of 12p was associated with a statistically significant greater likelihood of treatment failure. With diagnostic and possibly prognostic importance in germ cell tumors in males, the high frequency of i(12p) in our series of studies and in those of others indicates that it probably occurs as a very early defect in the development of these tumors. Further studies of chromosome 12 in males with these tumors are warranted.
Effects of sustained hypoxia on sternohyoid and diaphragm muscle during development
Authors: Jayne C. Carberry, Clodagh McMorrow, Aidan Bradford, James F.X. Jones, Ken D. O’Halloran
Journal: European Respiratory Journal (2013)

Sustained hypoxia is a dominant feature of respiratory disease. Despite the clinical significance, the effects of sustained hypoxia on the form and function of respiratory muscle during development are relatively underexplored. Wistar rats were exposed to 1 week of sustained hypoxia (ambient pressure 450 mmHg) or normoxia at various time points during development. Sternohyoid and diaphragm muscle contractile and endurance properties were assessed in vitro. Muscle succinate dehydrogenase and myosin heavy chain composition were determined. The role of reactive oxygen species in hypoxia-induced muscle remodelling was assessed. Sustained hypoxia increased sternohyoid muscle force and fatigue in early but not late development, effects that persisted after return to normoxia. Hypoxia-induced sternohyoid muscle fatigue was not attributable to fibre type transitions or to a decrease in oxidative capacity. Chronic supplementation with the superoxide scavenger tempol did not prevent hypoxia-induced sternohyoid muscle fatigue, suggesting that mechanisms unrelated to oxidative stress underpin hypoxia-induced maladaptation in sternohyoid muscle. Sustained hypoxia had no effect on diaphragm muscle fatigue. We conclude that there are critical windows during development for hypoxia-induced airway dilator muscle maladaptation. Sustained hypoxia-induced impairment of upper airway muscle endurance may persist into later life. Upper airway muscle dysfunction could have deleterious consequences for the control of pharyngeal airway calibre in vivo.
Enhanced cytoplasmic expression of desmocollin 3 in epidermal rete ridges of Dowling-Degos syndrome
Authors: M. Braun-Falco, J. Ring
Journal: British Journal of Dermatology (2003)

Journal Article Enhanced cytoplasmic expression of desmocollin 3 in epidermal rete ridges of Dowling–Degos syndrome Get access M. Braun‐Falco, M. Braun‐Falco Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteinerstr. 29, 80802 München, Germany E‐mail: mbf@lrz.tum.de Search for other works by this author on: Oxford Academic Google Scholar J. Ring J. Ring Klinik und Poliklinik für Dermatologie und Allergologie am Biederstein, Technische Universität München, Biedersteinerstr. 29, 80802 München, Germany E‐mail: mbf@lrz.tum.de Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 149, Issue 6, 1 December 2003, Pages 1293–1296, https://doi.org/10.1111/j.1365-2133.2003.05645.x Published: 01 December 2003
Human blood basophils do not act as antigen‐presenting cells for the major birch pollen allergen <scp>B</scp>et v 1
Authors: C. Kitzmüller, B. Nagl, S. Deifl, C. Walterskirchen, B. Jahn‐Schmid, G. J. Zlabinger, B. Bohle
Journal: Allergy (2011)

Abstract Background: Several studies in mice have recently shown that basophils can act as antigen‐presenting cells ( APC ) inducing T h2‐mediated immune responses against parasites or protease allergens. The aim of this study was to investigate whether human basophils function as APC for the major birch pollen allergen B et v 1. Methods: Fluorescently labeled B et v 1 was used to assess surface binding and internalization of allergen by basophils and different types of APC from birch pollen‐allergic and nonallergic individuals. Sorted basophils were analyzed in terms of up‐regulation of MHC class II and co‐stimulatory molecules in the absence and presence of IL ‐3 and IFN ‐γ by flow cytometry. Expression of proteins crucial for antigen presentation, namely cathepsin S and invariant chain, was determined. Basophils were used as APC in co‐culture experiments with B et v 1‐specific T ‐cell clones ( TCC s). Results: Basophils from birch pollen‐allergic donors very efficiently bound B et v 1 through I g E / F cε RI complexes on their surface. In contrast to professional APC , basophils did not internalize allergen and expressed marginal levels of cathepsin S and invariant chain. HLA ‐ DP , HLA ‐ DQ , CD 80/ CD 86, and CD 40 were absent from purified basophils even when stimulated with IL ‐3 plus IFN ‐γ. IL ‐3/ IFN ‐γ marginally up‐regulated HLA ‐ DR . B et v 1‐pulsed basophils failed to induce proliferative and cytokine responses in B et v 1‐specific, HLA ‐ DR ‐restricted TCC s. Conclusion: Human basophils neither internalize, process nor present B et v 1. Because B et v 1 is a highly relevant allergen, we conclude that basophils play no role as APC in I g E ‐mediated allergy in humans.