tbuckley/cabot-search huggingface dataset:
Increased Brain Activation During Working Memory in Cognitively Intact Adults With the APOE ε4 Allele
Authors: Heather A. Wishart, Andrew J. Saykin, Laura A. Rabin, Robert B. Santulli, Laura A. Flashman, Stephen J. Guerin, Alexander C. Mamourian, Dorothy R. Belloni, C. Harker Rhodes, Thomas W. McAllister
Journal: American Journal of Psychiatry (2006)

Objective: Altered patterns of brain activity during cognitive tasks have been demonstrated using functional magnetic resonance imaging (fMRI) in mild cognitive impairment and Alzheimer's disease. However, there have been few studies of adults at genetic risk for Alzheimer's disease prior to the onset of symptoms. The purpose of this study was to determine whether brain activation patterns associated with working memory differ as a function of apolipoprotein E (APOE) genotype in cognitively intact adults. Method: Participants were cognitively intact, healthy adults who completed genotyping, comprehensive neuropsychological testing, and structural and functional neuroimaging. Twenty-two participants had the APOE ε3/ε3 genotype, and 13 participants had the APOE ε3/ε4 genotype. The study employed an auditory verbal N-back task to probe working memory-related brain activity. Results: The ε3/ε3 and ε3/ε4 groups did not differ in demographic characteristics, cognitive ability, mood, or in-scanner task performance. The ε3/ε4 group showed greater activity during working memory in the medial frontal and parietal regions bilaterally and in the right dorsolateral prefrontal cortex. There were no regions in which the ε3/ε3 group showed greater activation than the ε3/ε4 group. Conclusions: These results indicate that differences in brain activity are evident in cognitively intact individuals who are at risk for late-onset Alzheimer's disease by virtue of their APOE allele status. As neuroprotective interventions become available, early detection will increase in importance. The combination of genetic and functional neuroimaging strategies may prove useful for monitoring individuals at risk for Alzheimer's disease before the onset of cognitive symptoms.
Pincer nail deformity as the main manifestation of Clouston syndrome
Authors: Y.‐H. Hu, Y.‐C. Lin, W.‐L. Hwu, Y.‐M. Lee
Journal: British Journal of Dermatology (2015)

Funding sources: National Taiwan University Hospital Fund. Conflicts of interest: none declared. Dear Editor, Pincer nail deformity is characterized by an increase in the transverse curvature along the longitudinal axis of the nail.1 Acquired pincer nails are not symmetrical. The most common causes are onychomycosis, psoriasis, tumours of the nail apparatus, and poorly fitting shoes.2 3 Pincer nail deformity may be associated with systemic diseases, such as renal failure.4 Hereditary pincer nail deformity is rare and only a few cases have been reported.5 Clouston syndrome is an autosomal dominant hidrotic ectodermal dysplasia initially suspected to be caused by a defect in the keratin proteins.6 It is characterized by alopecia, palmoplantar hyperkeratosis and nail dystrophy. In 1996, the GJB6 gene, encoding connexin‐30, was determined to be mutated in these patients.7 The c.31G>A (p.G11R) mutation was first identified in two unrelated French families, and other disease‐causing mutations in the gene were also identified.7 8 The spectrum of clinical manifestations of Clouston syndrome was later extended to include pachyonychia congenita,9 a group of ectodermal dysplasias with the most obvious phenotypic characteristics of subungual hyperkeratosis and palmoplantar keratoderma. Pachyonychia congenita is associated with mutations in keratins 6a, 6b, 16 and 17.10 11 Several families with nail abnormalities had previously been diagnosed as having pachyonychia congenita; subsequently GJB6 p.G11R and p.A88V mutations were identified, and those patients actually exhibited Clouston syndrome.9
Control of carbapenemase-producing Klebsiella pneumoniae: a region-wide intervention
Authors: C Gagliotti, V Cappelli, E Carretto, M Marchi, A Pan, P Ragni, M Sarti, R Suzzi, G A Tura, M L Moro, collective on behalf of the Emilia-Romagna Group for CPE Control
Journal: Eurosurveillance (2014)

Starting in 2010, there was a sharp increase in infections caused by Klebsiella pneumoniae resistant to carbapenems in the Emilia-Romagna region in Italy. A region-wide intervention to control the spread of carbapenemase-producing K. pneumoniae (CPKP) in Emilia-Romagna was carried out, based on a regional guideline issued in July 2011. The infection control measures recommended to the Health Trusts (HTs) were: phenotypic confirmation of carbapenemase production, active surveillance of asymptomatic carriers and contact isolation precautions for carriers. A specific surveillance system was activated and the implementation of control measures in HTs was followed up. A significant linear increase of incident CPKP cases over time (p&lt;0.001) was observed at regional level in Emilia-Romagna in the pre-intervention period, while the number of cases remained stable after the launch of the intervention (p=0.48). Considering the patients hospitalised in five HTs that provided detailed data on incident cases, a downward trend was observed in incidence after the release of the regional guidelines (from 32 to 15 cases per 100,000 hospital patient days). The spread of CPKP in Emilia-Romagna was contained by a centrally-coordinated intervention. A further reduction in CPKP rates might be achieved by increased compliance with guidelines and specific activities of antibiotic stewardship.
Open-label, pilot study examining sequential therapy with oral tacrolimus and topical tacrolimus for severe atopic dermatitis
Authors: Terrence Colin Keaney, Tina Bhutani, Priya Sivanesan, Grace D. Bandow, Sari Beth Weinstein, Lawrence C.C. Cheung, Farah Malick, John Koo
Journal: Journal of the American Academy of Dermatology (2012)
Oxidants increase paracellular permeability in a cultured epithelial cell line.
Authors: M J Welsh, D M Shasby, R M Husted
Journal: Journal of Clinical Investigation (1985)

Inflammation of epithelia is an important step in the pathophysiology of a wide variety of diseases. Because reactive oxygen metabolites are important effector molecules of acute inflammation, we examined the effect of oxidants on the barrier function of a cultured epithelium, Madin Darby Canine Kidney cells, by measuring the transepithelial electrical conductance, Gt, of monolayers grown on permeable supports. We found that H2O2, added directly or generated with glucose oxidase, increased Gt. Similar effects were observed with addition of xanthine and xanthine oxidase, a system which enzymatically generates superoxide radical O2-. The oxidant-induced increase in Gt was reversible if the exposure to oxidants was not prolonged (less than 20 min), and if the concentration of H2O2 was less than 5 X 10(-3) M. The increase in Gt suggested that oxidants increase the permeability of the paracellular pathway, a suggestion supported by an oxidant-induced increase in the permeability to 14C-mannitol, which primarily crosses epithelia via the extracellular route. In addition to functional changes in the epithelial monolayer, oxidants changed the cell morphology; after H2O2 exposure, the cells tended to pull apart, most prominently at their basolateral surfaces. These changes were heterogeneous with most areas showing no changes. Some of the morphologic changes could be reversed if the exposure to H2O2 was limited. We also observed a disruption of the normal pattern of the actin-cytoskeleton, particularly in the area of cell to cell junctions, as demonstrated by fluorescent staining of f-actin with rhodamine phallicidin. These functional and structural findings indicate that oxidants increase the permeability of the paracellular pathway in a cultured epithelium. The changes can be reversible, and are accompanied by alterations in organization of the cell cytoskeleton. These studies demonstrate the dynamic nature of the interaction between epithelial cells and oxygen metabolites.
Abstract 1211: Application of PDX models in mimic clinical trials for anticancer drug development
Authors: Taiping Chen, Yan Hu, Hui Zhang, Xiaoqin Sun
Journal: Cancer Research (2014)

Abstract The utilization of patient derived xenograft (PDX) models has recently gained huge recognition in anticancer drug research and development. Based on molecular profiling the resemblance between patient tumor and PDX is significantly closer than that between patient tumor and traditional cell lines. Therefore, new initiatives are proposed to apply PDX models in in vivo target validation, clinical relevant MOA study, tumor addiction and heterogeneity characterization, sensitivity and resistance to chemotherapeutics and targeted therapeutics, and even mimic clinical trials for cancer type indication. In order to evaluate the efficacious and pharmacodynamic responses in PDX models and support the rationale for mimic clinical trials, we freshly established PDX models from the patients with colorectal (CRC), lung, pancreatic, gastric, liver cancers. The tumor take rate was very high for CRC and lung cancer patient, 90% and 70% respectively. Irinotecan and Cetuximab for colorectal PDX model, Docetaxel and Tarceva for lung PDX model were organized as mimic clinical trials. The high tumor take-rate (9 of 10 colorectal; 7 of 10 lung cancer) will ascertain pharmacologic significance when tested in mimic clinical trials. To illustrate the usefulness of this platform, we first evaluate the responders and non-responders based on efficacious trials. Then we will further continue with single dose for pharmacodynamic (PD) biomarker evaluation from selected drug targets or related pathway regulators. Efficacy results and corresponding PD biomarkers confirmed in this approach have potential to be used for cancer indication and patient stratification in later phase II clinical trials. Citation Format: Taiping Chen, Yan Hu, Hui Zhang, Xiaoqin Sun. Application of PDX models in mimic clinical trials for anticancer drug development. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1211. doi:10.1158/1538-7445.AM2014-1211
Nonmelanoma Skin and Mucosal Cancers After Hematopoietic Cell Transplantation
Authors: Wendy Leisenring, Debra L. Friedman, Mary E.D. Flowers, Jeffrey L. Schwartz, H. Joachim Deeg
Journal: Journal of Clinical Oncology (2006)

To evaluate the incidence of and risk factors for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in survivors of hematopoietic cell transplantation (HCT).The impact of patient-, disease-, treatment-, and toxicity-related factors on risk of BCC and SCC was determined in a retrospective cohort study of 4,810 patients who received allogeneic HCT and who survived for at least 100 days.Among allogeneic HCT recipients, 237 developed at least one skin or mucosal cancer (BCC, n = 158; SCC, n = 95). Twenty-year cumulative incidences of BCC and SCC were 6.5% and 3.4%, respectively. Total-body irradiation was a significant risk factor for BCC (P = .003), most strongly among patients younger than 18 years old at HCT (P = .02, interaction). Light-skinned patients had an increased risk of BCC (P = .01). Acute graft-versus-host disease (GVHD) increased the risk of SCC (P = .02), whereas chronic GVHD increased the risk of both BCC (P = .01) and SCC (P < .001).This analysis suggests that immutable factors, such as age and complexion, have a significant impact on BCC and SCC. However, specific treatment (radiotherapy) and transplantation complications (GVHD) may modify that risk. These additional risk factors suggest the contribution of immunologic mechanism DNA and tissue repair in the development of BCC and SCC. We confirm previous reports that exposure to ionizing radiation increases the risk of BCC but not SCC. Survivors of HCT should be monitored for the development of BCC and SCC and use preventive strategies.
Comparative proteomic analysis between normal skin and keloid scar
Authors: C.T. Ong, Y.T. Khoo, A. Mukhopadhyay, J. Masilamani, D.V. Do, I.J. Lim, T.T. Phan
Journal: British Journal of Dermatology (2010)

Journal Article Comparative proteomic analysis between normal skin and keloid scar Get access C.T. Ong, C.T. Ong Department of Surgery Yong Loo Lin School of Medicine Search for other works by this author on: Oxford Academic Google Scholar Y.T. Khoo, Y.T. Khoo Department of Surgery Yong Loo Lin School of Medicine Search for other works by this author on: Oxford Academic Google Scholar A. Mukhopadhyay, A. Mukhopadhyay Department of Surgery Yong Loo Lin School of Medicine Search for other works by this author on: Oxford Academic Google Scholar J. Masilamani, J. Masilamani Department of Surgery Yong Loo Lin School of Medicine Search for other works by this author on: Oxford Academic Google Scholar D.V. Do, D.V. Do Centre for Craniofacial & Regenerative Biology Search for other works by this author on: Oxford Academic Google Scholar I.J. Lim, I.J. Lim Department of Surgery Yong Loo Lin School of Medicine Search for other works by this author on: Oxford Academic Google Scholar T.T. Phan T.T. Phan Department of Surgery Yong Loo Lin School of MedicineCentre for Craniofacial & Regenerative BiologyFaculty of Dentistry and NUS Tissue Engineering and Stem Cell Research Program, National University of Singapore, Singapore Thang T. Phan. E‐mail: surptt@nus.edu.sg Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 6, 1 June 2010, Pages 1302–1315, https://doi.org/10.1111/j.1365-2133.2010.09660.x Published: 01 June 2010
Dynamic Evolution of Base Composition: Causes and Consequences in Avian Phylogenomics
Authors: B. Nabholz, A. Kunstner, R. Wang, E. D. Jarvis, H. Ellegren
Journal: Molecular Biology and Evolution (2011)

Resolving the phylogenetic relationships among birds is a classical problem in systematics, and this is particularly so when it comes to understanding the relationships among Neoaves. Previous phylogenetic inference of birds has been limited to mitochondrial genomes or a few nuclear genes. Here, we apply deep brain transcriptome sequencing of nine bird species (several passerines, hummingbirds, dove, parrot, and emu), using next-generation sequencing technology to understand features of transcriptome evolution in birds and how this affects phylogenetic inference, and combine with data from two bird species using first generation technology. The phylogenomic data matrix comprises 1,995 genes and a total of 0.77 Mb of exonic sequence. First, we find an unexpected heterogeneity in the evolution of base composition among avian lineages. There is a pronounced increase in guanine + cytosine (GC) content in the third codon position in several independent lineages, with the strongest effect seen in passerines. Second, we evaluate the effect of GC content variation on phylogenetic reconstruction. We find important inconsistencies between the topologies obtained with or without taking GC variation into account, each supporting different conclusions of past studies and also influencing hypotheses on the evolution of the trait of vocal learning. Third, we demonstrate a link between GC content evolution and recombination rate and, focusing on the zebra finch lineage, find that recombination seems to drive GC content. Although we cannot reveal the causal relationships, this observation is consistent with the model of GC-biased gene conversion. Finally, we use this unparalleled amount of avian sequence data to study the rate of molecular evolution, calibrated by fossil evidence and augmented with data from alligator transcriptome sequencing. There is a 2- to 3-fold variation in substitution rate among lineages with passerines being the most rapidly evolving and ratites the slowest. This study illustrates the potential of next-generation sequencing for phylogenomic studies but also the pitfalls when using genome-wide data with heterogeneous base composition.
Novel Angiogenic Signaling Pathways and Vascular Targets
Authors: Roy Bicknell, Adrian L. Harris
Journal: The Annual Review of Pharmacology and Toxicology (2004)

Intense investigation into the molecular basis of angiogenesis is rapidly revealing novel signaling pathways involved in the generation of new vasculature. These range from elucidation of the mechanism by which hypoxia initiates expression of a proangiogenic gene repertoire via the hypoxia-inducible transcription factors (HIFs) to molecular pathways involved in extra- and intracellular signaling during new vessel formation. Extracellular pathways include those of the Notch/delta, ephrin/Eph receptor and roundabout/slit families, and intracellular pathway members of the hedgehog and sprouty families. The involvement of these pathways in angiogenesis is discussed, together with some comments on recently identified targets in the vasculature that present new therapeutic opportunities.
Inhaled micronised gentamicin powder: a new delivery system.
Authors: J M Goldman, S M Bayston, S O'Connor, R E Meigh
Journal: Thorax (1990)

Forty patients undergoing routine bronchoscopy were randomised to receive inhaled micronised gentamicin powder (180 mg) or nebulised gentamicin solution (160 mg) one hour before the procedure. Similar levels of gentamicin were detected in bronchoalveolar lavage fluid in the two groups (micronised powder (n = 20) 9.3 (SD 9.3) mg/l, nebulised solution (n = 20) 8.0 (7.8) mg/l). The micronised gentamicin powder preparation caused cough in half the patients but this did not stop their receiving a full dose. Dry powder gentamicin may be a convenient formulation for long term inhaled treatment if the problem of cough can be overcome.
Profile of Circulating Vasoactive Substances in Hemorrhagic Shock and Their Pharmacologic Manipulation
Authors: Barbara A. Jakschik, Garland R. Marshall, Janet L. Kourik, Philip Needleman
Journal: Journal of Clinical Investigation (1974)

(a) Hemorrhage in dogs (to 45-50 mm Hg) was associated with a 10-fold increase in plasma renin activity (PRA) which remained elevated throughout the time-course of shock including the irreversible (decompensation) stage. The presence of angiotensin II (AII) in arterial blood was demonstrated by the bloodbathed organ technique and confirmed by blockade with specific AII antagonists (cysteine(8)-AII or isoleucine(8)-AII). The contribution of AII to systemic peripheral resistance during hemorrhage shock in dogs was established by administering AII antagonists which immediately cause a further fall in blood pressure.(b) Plasma catecholamines (CA) steadily increased during hemorrhage and peaked during compensation (a 100-fold increase). The CA decreased progressively during decompensation.(c) Prostaglandin (PG) E-like material was observed in arterial blood for 15-60 min (after hemorrhage); the peak arterial concentration was 2.6 ng/ml blood. Indomethacin (i.v., before 80% of maximum bleedout): (i) confirmed the presence of PGE, (ii) increased blood pressure, and (iii) increased blood loss.(d) Thus: peripheral resistance during hemorrhagic shock seems temporally correlated with blood CA levels (and not PRA), and the renin-AII system contributes to the maintenance of vascular resistance and may markedly decrease perfusion of organs, such as kidney; the administration of the proper combination of specific antagonists of vasoconstrictor humoral substances may radically improve organ perfusion and could contribute to ultimate recovery from hemorrhagic shock.
Intracoronary adenosine as an adjunct to combined use of primary angioplasty in acute myocardial infarction: Beneficial effects on angiographically assessed no-reflow
Authors: Mario Marzilli, Paolo Marraccini, Enri Gliozheni, Enrico Orsini, Eugenio Picano
Journal: Journal of the American College of Cardiology (1996)
Regional Hemodynamic Effects of a Digitalis Glycoside in the Conscious Dog with and without Experimental Heart Failure
Authors: CHARLES B. HIGGINS, STEPHEN F. VATNER, EUGENE BRAUNWALD
Journal: Circulation Research (1972)

The effects of intravenous ouabain (G-strophanthin), 20 µg/kg, on the superior mesenteric, renal, and external iliac beds were studied over a 30-minute period in eight normal conscious dogs before, and in five of them after, cholinergic blockade and in six conscious dogs with heart failure produced by tricuspid avulsion and progressive pulmonary stenosis. Blood flows were measured with Doppler ultrasonic and electromagnetic flowmeters. In normal dogs, prior to cholinergic blockade, ouabain caused early increases in mesenteric, renal, and external iliac resistances but later, between 15 and 30 minutes, mesenteric resistance decreased below the control level while renal and external iliac resistances remained elevated. After cholinergic blockade, the ouabain-induced alterations in renal and iliac resistance were unaltered, but the later decline in resistance in the mesenteric bed was reversed, resulting in sustained constriction. The late decline in mesenteric resistance also was not observed in the conscious animal after the injection of ouabain, 5 µg/kg, directly into the mesenteric artery or in the majority of dogs given ouabain intravenously after having been anesthetized with pentobarbital sodium. In the conscious dogs with heart failure, ouabain resulted in increased renal and iliac resistances initially, and in vasodilatation later while mesenteric resistance fell initially and remained below control for the entire 30 minutes. Thus, in the normal conscious dog, ouabain causes vasoconstriction in the regional vascular beds, apparently by its direct vascular action, and, in addition, a cholinergically mediated vasodilatation in the mesenteric bed. In the conscious dog with heart failure, ouabain increases blood flow to all beds, reducing the compensatory vasoconstriction of the low output state.
Influence of Genomic Loci on Measures of Chronic Kidney Disease in Hypertensive Sibships
Authors: Stephen T. Turner, Sharon L.R. Kardia, Thomas H. Mosley, Andrew D. Rule, Eric Boerwinkle, Mariza de Andrade
Journal: Journal of the American Society of Nephrology (2006)

Genomewide linkage analyses were conducted of serum creatinine, estimated GFR (eGFR), and urine albumin-creatinine ratio (UACR) in search of genetic susceptibility loci for chronic kidney disease in 1351 black (median age 63 yr, 70% women, 79% hypertensive) and 1022 white individuals (median age 61 yr, 56% women, 75% hypertensive) from sibships in which two or more members had essential hypertension diagnosed before age 60 yr. After adjustment for gender, age, diabetes, and use of angiotensin inhibitors, the logarithm-transformed measure of serum creatinine was heritable in both ethnic groups (0.45 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]), as was eGFR (0.52 in black individuals [P < 0.001]; 0.39 in white individuals [P < 0.001]). Log UACR was heritable in black individuals (0.30, P < 0.001) but not in white individuals (0.12; P = 0.059). In black individuals, the univariate maximum multipoint logarithm of odds scores (MLS) were observed on chromosome 7 for log serum creatinine (MLS = 3.65, at 43 cM from pter; P = 0.00002) and eGFR (MLS = 2.52, at 45 cM from pter; P = 0.00033) and for log UACR (MLS = 2.91, at 112 cM from pter; P = 0.00012). In white individuals, only one MLS for log serum creatinine and one for eGFR achieved the logarithm of odds score criterion for "suggestive" evidence of linkage (2 < or = MLS < 3), both on chromosome 3 (at 211 and 209 cM, respectively); however, none did so for log UACR. In black individuals, bivariate linkage analyses of log serum creatinine and pulse pressure (i.e., systolic-diastolic BP) provided "suggestive" evidence of a region on chromosome 5 with pleiotropic effects on both traits (MLS = 3.62, at 85 cM from pter; P = 0.00023). These findings support the utility of genetic linkage analyses for identification of novel risk factors that influence measures of chronic kidney disease, particularly among black individuals.