tbuckley/cabot-search huggingface dataset:
Filaggrin breakdown products determine corneocyte conformation in patients with atopic dermatitis
Authors: Christoph Riethmuller, Maeve A. McAleer, Sjors A. Koppes, Rawad Abdayem, Jonas Franz, Marek Haftek, Linda E. Campbell, Stephanie F. MacCallum, W.H. Irwin McLean, Alan D. Irvine, Sanja Kezic
Journal: Journal of Allergy and Clinical Immunology (2015)

BackgroundLoss-of-function (LOF) mutations in the filaggrin gene (FLG) are a well-replicated risk factor for atopic dermatitis (AD) and are known to cause an epidermal barrier defect. The nature of this barrier defect is not fully understood. Patients with AD with FLG LOF mutations are known to have more persistent disease, more severe disease, and greater risk of food allergies and eczema herpeticum. Abnormalities in corneocyte morphology have been observed in patients with AD, including prominent villus-like projections (VP); however, these ultrastructural features have not been systematically studied in patients with AD in relation to FLG genotype and acute and convalescent status.ObjectiveWe sought to quantitatively explore the relationship between FLG genotype, filaggrin breakdown products (natural moisturizing factor [NMF]), and corneocyte morphology in patients with AD.MethodsWe studied 15 children at first presentation of AD and after 6 weeks of standard therapy. We applied atomic force microscopy to study corneocyte conformation in patients with AD stratified by FLG status and NMF level. By using a new quantitative methodology, the number of VPs per investigated corneocyte area was assessed and expressed as the Dermal Texture Index score. Corneocytes were also labeled with an anti-corneodesmosin antibody and visualized with scanning electron microscopy.ResultsWe found a strong correlation between NMF levels and Dermal Texture Index scores in both acute and convalescent states (respective r = −0.80 and −0.75, P < .001 and P = .002). Most, but not all, VPs showed the presence of corneodesmosin abundantly all over the cell surface in homozygous/compound heterozygous FLG patients and, to a lesser extent, in heterozygous and wild-type patients.ConclusionsNMF levels are highly correlated with corneocyte morphology in patients with AD. These corneocyte conformational changes shed further insight into the filaggrin-deficient phenotype and help explain the barrier defect in patients with AD with FLG LOF mutations.
Outbreak of severe acute respiratory syndrome in a tertiary hospital in Singapore, linked to an index patient with atypical presentation: epidemiological study
Authors: K. Y. Chow
Journal: BMJ (2004)

<h3>Abstract</h3> <b>Objective</b> To describe an outbreak of severe acute respiratory syndrome (SARS) in a tertiary hospital in Singapore, linked to an index patient with atypical presentation, and the lessons learnt from it. <b>Design</b> Descriptive study. <b>Setting</b> A tertiary hospital in Singapore. <b>Participants</b> Patients, healthcare workers, and visitors who contracted SARS in Singapore General Hospital. <b>Main outcome measures</b> Probable SARS as defined by the World Health Organization. <b>Results</b> The index patient presented with gastrointestinal bleeding, initially without changes to his chest radiograph. Altogether 24 healthcare workers, 15 patients, and 12 family members and visitors were infected. The incubation period ranged from three to eight days. Only 13 patients were isolated on their dates of onset. <b>Conclusions</b> Atypical presentation of SARS infection must be taken into consideration when managing patients with a history of contact with SARS patients. The main gap in the containment strategy in this outbreak was the failure to identify the index patient as someone who had been discharged from a ward in another hospital that managed probable SARS cases. Strict infection control measures, a good surveillance system, early introduction of isolation procedures, and vigilant healthcare professionals are essential for controlling outbreaks.
Abstract MP29: Patient Characteristics And Outcomes Associated With In-hospital Onset Of Acute Decompensated Heart Failure
Authors: Corey A Kalbaugh, Patricia P Chang, Kunihiro Matsushita, Sunil K Agarwal, Melissa Caughey, Hanyu Ni, Wayne Rosamond, Lisa Wruck, Laura Loehr
Journal: Circulation (2014)

Introduction: There has been little focus on hospitalized acute decompensated heart failure (ADHF) that develops after admission, which may occur because of comorbid conditions, over-administration of fluid or post-surgical complications. Aims: To compare patient characteristics, case fatality, and hospital length of stay (LOS) associated with ADHF that develops after hospital admission as compared to those with ADHF at admission. Methods: Hospitalizations with possible ADHF were sampled, based on HF ICD codes, among those aged &gt; 55 years from the four communities of the Atherosclerosis Risk in Communities Study (2005-2010). Medical records were abstracted with events classified by physician panel or computer classified. Case fatality was obtained through the National Death Index. We identified 4,503 (unweighted) events with definite/probable ADHF, after excluding those with unknown time of decompensation (n=81), hospital transfers (n=102), and race other than black or white (n=118). Demographic and clinical characteristics were compared by ADHF onset (at/after admission). Logistic regression was used to evaluate the association of ADHF onset with in-hospital mortality, and 28-days and one-year mortality, adjusted for demographics and comorbidity. Linear regression was used to evaluate the association of ADHF onset with log-transformed hospital LOS, adjusted for demographics. All analyses were weighted to account for the stratified sampling design. Results: Of 21,052 (weighted) ADHF events, 7.4% (n=1561) developed ADHF after admission. Patients with ADHF occurring after admission were older (mean: 79 vs. 75 years), and more likely white and female. Those with ADHF at admission were more likely to have a positive smoking history, COPD, and to be on dialysis. Presence of diabetes, hypertension and coronary artery disease were not significantly different between groups. In hospital mortality (16.5% vs. 6.3%; OR= 2.7, 95% CI=1.9-3.8) and 28-day mortality (23.9% vs. 10.1%; OR= 2.4, 95% CI=1.7-3.4) was higher among those who developed ADHF after admission. One-year case fatality was similar (39.4% vs. 33.6%; OR= 1.2, 95% CI=0.9-1.6). Unadjusted mean LOS was longer for those with ADHF occurring after admission (12.8 days, 95% CI=11.8-13.8) than those with ADHF at admission (7.2 days, 95% CI=6.8-7.6). The adjusted and geometric mean LOS was 1.3 days (95% CI=1.2-1.4) longer for those who developed ADHF after admission. Conclusion: Although patients with ADHF onset after admission were slightly older, differences in comorbidity do not indicate an easily identifiable subgroup for closer in-hospital monitoring. Development of ADHF after admission was associated with an alarmingly high early case fatality and longer hospital LOS compared to those with ADHF at hospital admission.
Attempts to Optimise Induction and Consolidation Chemotherapy in Patients with Acute Myeloid Leukaemia: Results of the MRC AML15 Trial.
Authors: Alan K Burnett, Robert K Hills, Donald Milligan, Ann E. Hunter, Anthony H. Goldstone, Archie Prentice, Brenda ES Gibson, Lars Kjeldsen, John AL Yin, Keith Wheatley, Nigel H. Russell
Journal: Blood (2009)
Abstract 16765: Clinical Outcomes and Thromboembolic Complications Related to Recombinant Factor VII Activated Use for Refractory Medical Bleeding After Pediatric Cardiac Surgery
Authors: Michael J Troncone, Leonardo R Brandao, Christopher A Caldarone, Cedric Manlhiot, Brian W McCrindle, Steven M Schwartz, Glen Van Arsdell, V B Sivarajan
Journal: Circulation (2011)

Introduction: Resolution of refractory bleeding after cardiac surgery with Recombinant Factor VII activated (rFVIIa) has been demonstrated. Increased use for this indication and resultant thromboembolic complications (TCs) have been described. Hypothesis: rFVIIa use after pediatric cardiac surgery reduces postoperative bleeding without increasing the risk of TCs or death. Methodology: A matched case-control analysis of pediatric inpatients from 2004-2009 was performed. Cases received rFVIIa intraoperatively or in the intensive care unit after cardiac surgery. Cases were matched 1:1 to controls by age and operation. Demographic and perioperative clinical variables were collected. Primary outcomes of interest were death or TCs; secondary outcomes were blood product utilization, chest tube drainage, duration of ventilation and length of stay. TCs were defined as intravascular thrombosis (venous, arterial, intracardiac), cardioembolic stroke or pulmonary embolism confirmed by radiologic methods, surgery, catheterization or autopsy performed at any point after the index operation. Results: 50 cases were reviewed; cases had median weight at operation of 6 kg. Index operations for which rFVIIa was given included single ventricle palliations(26%) and heart transplantation(24%). Cases had longer cardiopulmonary bypass (157 vs 124 minutes, p=0.003) time with greater postoperative red blood cell (13 vs 10 ml/kg; p=0.008) and platelet (29 vs 6 ml/kg; p=0.008) transfusion requirements. The median rFVIIa dose was 150 mcg/kg with thirty-six (72%) patients receiving it intraoperatively; bleeding reduced significantly after rFVIIa administration (10.5 vs 2.0 mL/kg/h; p=0.001). Cases had a longer duration of postoperative ventilation (4 vs 1.5 days, p=0.02) and hospital stay (19 vs 9 days, p=0.03). After rFVIIa use, rate of TCs (32 vs 26%, p=0.66) and mortality (32 vs 20%, p=0.25) were comparable to controls. Conclusions: rFVIIa dramatically reduces refractory bleeding after pediatric cardiac surgery; these patients still have increased blood product requirements and length of stay. There does not appear to be an incremental risk of TCs after rFVIIa administration. This may be reflective of the high burden of TCs in this population.
Abstract 19138: Reperfusion Therapy for ST-Elevation Acute Myocardial Infarction in Eastern Europe: The ISACS-TC Registry
Authors: Edina Cenko, Sasko Kedev, Zorana Vasiljevic, Maria Dorobantu, Olivija Gustiene, Irfan Daullxhiu, Božidarka Kneževic, Davor Milicic, Mirza Dilic, Dijana Trninic, Olivia Manfrini, Raffaele Bugiardini
Journal: Circulation (2014)

Introduction:  Widespread availability of tertiary hospitals with catheterization facilities, although vigorously promoted, has yet to become a reality in many countries with economy in transition.   Hypothesis:  To evaluate the clinical profile and mortality of patients who were hospitalized with a diagnosis of STEMI, and either received reperfusion therapy or remained without reperfusion in Eastern Europe.   Methods:  Data were obtained from the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC; NCT01218776) on 6690 STEMI patients admitted to 57 hospitals in 8 Eastern Europe countries (Bosnia and Herzegovina, Croatia, Kosovo, Lithuania, Macedonia, Montenegro, Romania and Serbia) from January 2010 to May 2014. The primary endpoint was in-hospital mortality. Estimates of the ORs and 95%CI were obtained by multivariable logistic regression analysis.   Results:  The prevalent reperfusion strategies were: pPCI in Croatia (87.7%), Lithuania (81.1%), Macedonia ( 93.6%) and Serbia (69.1%) and fibrinolysis in Bosnia and Herzegovina (50.4%), Kosovo (22.6%), Montenegro (51.3%) and Romania (37.0%). Of the overall population, 1191 patients (17.8%) received fibrinolysis, 3547 patients (53.0%) underwent pPCI, and 1952 (29.2%) received no reperfusion therapy. The rates of non reperfused patients ranged from 1.9% to 77.4%, in Lithuania and Kosovo, respectively. Mortality rates were higher in non reperfused patient (16.0% vs. 5.3% in the pPCI group and 7.1% in fibrinolysis group). After adjustment, female sex (OR:1.26 CI: 1.08-1.47), age ≥ 65 yr (OR: 1.14 CI: 1.06-1.22), prior MI (OR: 1.82 CI:1.47-2.25), prior CABG (OR: 2.51 CI: 1.39-4.54), peripheral artery disease (OR: 2.91 CI: 1.90-4.46), Killip class ≥ 2 (OR: 1.88 CI: 1.57-2.25), and time to admission >12 h (OR: 7.12 CI: 6.09-8.32), were all independent variables associated with no reperfusion therapy.   Conclusions:  A substantial number of patients are still not offered any reperfusion therapy in many countries with economy in transition. Reperfusion therapies are mostly applied to relatively lower-risk patients. Due to the dishomogeneity of centers enrolled (secondary vs. tertiary), a direct comparison between countries should be performed with caution.
Abstract 2859: The genetic polymorphisms of <i>ATG5</i> and <i>COL4A3</i> are associated with the prognosis of patients with esophageal squamous cell carcinoma
Authors: Jang-Ming Lee, Pei-Wen Yang, Tzu-Hsuan Chiang, Ya-Chuan Huang, Ching-Yueh Hsieh
Journal: Cancer Research (2014)

Abstract PURPOSE: To investigate the association between the prognosis of patients with esophageal squamous cell carcinoma (ESCC) and the autophagy or collagen related single nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: The study was analyzed retrospectively. A total of 570 patients diagnosed with ESCC were enrolled in the study and randomly assigned to a training set (n=188) or replication set (n=382). The genotypes of 16 candidate SNPs involved in autophagy or collagen-related functions were analyzed using iPLEX Gold technology from the genomic DNA of peripheral leukocytes. The association of the genotypes and the overall survival or progression-free survival of patients was analyzed by multivariate Cox regression analysis and Kaplan-Meier survival function. RESULTS: Among these subjects, 239 patients were with early stage (stage IIa or earlier), and 331 patients were with advanced stages (stage IIb or advanced). In patients with early stages, the genetic variants of ATG5:rs1322178, ATG5:rs3804329 and COL4A3: rs28381984 was associated with increased risk of death in the training set. The associations were confirmed in the replication set and in the combined set (HR[95 % CI]=2.47 [1.31-4.65], P=0.005 in ATG5:rs1322178; HR[95 % CI]=2.16[1.08-4.31], P=0.029 in ATG5:rs3804329; HR[95 % CI]=1.48[1.00-2.20], P=0.052 in COL4A3: rs28381984, in combined set). In cumulative effect analysis of multiple SNPs, patients carrying the unfavorable genotypes at all these 3 genes exhibited a 3.87 fold increasd risk of death in early ESCC patients (HR[95 % CI]=3.87 [1.37-10.93], P=0.011). Finally, the Kaplan-Meier survival curves were constructed for overall survival by the number of unfavorable genotypes. The overall survival duration differed significantly between those with 0, 1, 2, and 3 cumulative unfavorable genotypes (log-rank P=0.012). CONCLUSION: The hereditary genetic polymorphisms of ATG5 and COL4A3 genes can serve as prognostic predictors of the patients with early ESCC. Citation Format: Jang-Ming Lee, Pei-Wen Yang, Tzu-Hsuan Chiang, Ya-Chuan Huang, Ching-Yueh Hsieh. The genetic polymorphisms of ATG5 and COL4A3 are associated with the prognosis of patients with esophageal squamous cell carcinoma. [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 2859. doi:10.1158/1538-7445.AM2014-2859
Abstract 15489: Hematopoietic PI3-Kinase δ-Deficiency Exacerbates Lesional Macrophage Infiltration and Atherosclerosis in LDLR-/- Mice
Authors: Mario Zierden, Christopher Millarg, Marius Vantler, Eva Berghausen, Stephan Baldus, Stephan Rosenkranz
Journal: Circulation (2014)

Atherosclerosis and its consequences such as myocardial infarction and ischemic stroke remains the leading cause of death in western countries. Atherosclerosis is a chronic inflammatory disease of arterial blood vessels, critically involving macrophages, dendritic cells and T lymphocytes. Leukocytes highly express the catalytic phosphoinositide 3-kinase isoform p110δ (PI3Kδ), exerting a key role in the regulation of immune responses including activation, differentiation and effector function of lymphocytes. Therefore, PI3Kδ represents a promising target for the modulation of inflammatory processes during atherogenesis. To investigate the role of leukocytic PI3Kδ during atherogenesis, lethally irradiated LDLR -/- mice were either transplanted with bone marrow from PI3Kδ -/- or PI3Kδ +/+ mice. After recovery, recipient mice were fed an atherogenic diet for 6 weeks. Hypercholesterolemic PI3Kδ -/- recipient LDLR -/- mice displayed a profound reduction of peripheral B and T cells as well as strongly impaired CD4 + T-cell activation, T-helper 1 response and regulatory T-cell numbers in paraaortic lymph nodes and spleen compared with PI3Kδ +/+ transplanted controls. Surprisingly, the profound impairment of the adaptive immune system by PI3Kδ-deficiency caused a considerable aggravation of atherosclerosis in LDLR -/- mice. Atherosclerotic lesion area at the aortic root and abdominal aorta of PI3Kδ -/- recipient LDLR -/- mice was significantly increased by 72% and 218% compared with PI3Kδ +/+ recipients, respectively (n = 10[[Unable to Display Character: &amp;#8211;]]20; P &lt; 0.001). Importantly, atherosclerotic lesions of PI3Kδ-deficient LDLR -/- mice were characterized by a lower fraction of CD4 + T cells and a higher proportion of MOMA-2 + monocytes/macrophages compared with controls despite unaltered circulating monocyte subsets. Thus, PI3Kδ-deficiency in mononuclear phagocytes may contribute to enhanced plaque growth. In summary, we demonstrate that hematopoietic PI3Kδ plays a crucial role in regulating innate and adaptive immune responses within the arterial wall by exerting protective functions during atherogenesis. Current studies aim to dissect PI3Kδ-dependent mechanisms that modulate inflammatory and regulatory processes in multiple stages of atherosclerosis.
Recombinant mite allergens
Authors: M. D. Chapman, A. M. Smith, L. D. Vailes, L. K. Arruda
Journal: Allergy (1997)

The introduction of molecular cloning techniques has led to advances in allergen identification and sequencing, production of recombinant allergens, identification of B‐cell and T‐cell epitopes, and tertiary structural analysis of allergen molecules. Over 10 groups of mite allergens have been cloned from Dermatophagoides spp., as well as several homologous allergens from Euroglyphus maynei, Lepidoglyphus destructor , and Blomia tropicalis. The availability of these allergens has made it feasible to consider their use for both diagnostic and therapeutic purposes. Several recombinant Dermatophagoides allergens show comparable reactivity on skin testing and in serologic assays to natural allergens, and cocktails of the recombinant proteins could be used as diagnostic reagents. New technologies have been developed for detection of allergen‐specific IgE and for environmental allergen detection using rapid diagnostic tests. Novel approaches to immunotherapy are also being investigated, including T‐cell‐peptide‐based vaccines, allergen variants which lack IgE reactivity, and naked DNA vaccines. The application of allergen biotechnology should lead to improvements in the management of mite‐allergic patients with asthma and represents a logical step toward reducing asthma mortality and morbidity.
VEGF did not enhance lung metastatic potential of human osteosarcoma cells
Authors: Shu-Fang Jia, Hui Guan, Xiaoping Duan, Eugenie S. Kleinerman
Journal: Cancer Research (2006)

4330  Our previous studies demonstrated that Fas expression inversely correlated with the metastatic potential of osteosarcoma (OS) cells in a nude mouse model. Parental SAOS-2 human OS cells have high Fas expression and do not form lung metastases following iv injection while the LM7 subline with low Fas expression is highly metastasis to the lungs. Upregulating Fas expression in LM7 cells by transfection of the Fas gene (LM7/Fas) significantly decreased lung metastases. The purpose of this study was to determine whether upregulating the expression of VEGF also affected lung metastatic potential. LM7 and LM7/Fas cells were transfected with pcDNA4 plasmid expressing VEGF165. Following transfection the expression of VEGF protein (measured by ELISA) increased 7.4- to 11.1- fold compared to LM7/neo cells, & 5.1 to 17.5 fold compared with LM7/Fas/neo cells. The Fas expression (quantified by flow cytometric analysis) was unchanged following VEGF transfection. The doubling time was reduced from 32.3 hrs in LM7/neo cells to 21.5 hrs in LM7/VEGF cells (p=0.038). However, the doubling time did not change in LM7/Fas/VEGF cells. To assess the in vivo effect of VEGF-transfection on metastases potential, mice were iv injected with 1×106 LM7, LM7/neo, LM7/VEGF, LM7/Fas, LM7/Fas/neo, LM7/Fas/VEGF cells. The mice were sacrificed 12 weeks later and the number of lung metastases quantified. There was not change in metastatic potential in the LM7/Fas/VEGF cells compared with LM7/Fas/neo cells. We therefore conclude that unlike Fas expression, which was inversely correlated with lung metastatic potential, increasing the VEGF expression in LM7 or LM7/Fas cells did not increase lung metastatic potential. .
Thyrotropin-releasing Hormone Stimulation of Prolactin Release from Clonal Rat Pituitary Cells
Authors: Marvin C. Gershengorn, Sylvia T. Hoffstein, Mario J. Rebecchi, Elizabeth Geras, Brian G. Rubin
Journal: Journal of Clinical Investigation (1981)

Thyrotropin-releasing hormone (TRH) stimulates prolactin release and 45Ca2+ efflux from GH3 cells, a clonal strain of rat pituitary cells. Elevation of extracellular K+ also induces prolactin release and increases 45Ca2+ efflux from these cells. In this report, we distinguish between TRH and high K+ as secretagogues and show that TRH-induced release of prolactin and 45Ca2+ is independent of the extracellular Ca2+ concentration, but the effect of high K+ on prolactin release and 45Ca2+ efflux is dependent on the concentration of Ca2+ in the medium. The increment in 45Ca2+ efflux induced by 50 mM K+ during perifusion was reduced in a concentration-dependent manner by lowering extracellular Ca2+ from 1,500 to 0.02 μM (by adding EGTA), whereas 1 μM TRH enhanced 45Ca2+ efflux similarly over the entire range of extracellular Ca2+ concentrations. Although 50 mM K+ caused release of 150 ng prolactin from 40 × 106 GH3 cells exposed to 1,500 μM Ca2+ (control), reduction of extracellular Ca2+ to 2.8 μM decreased prolactin release caused by high K+ to <3% of controls and no prolactin release was detected after exposure to 50 mM K+ in medium with 0.02 μM free Ca2+. In contrast, TRH caused release of 64 ng of prolactin from 40 × 106 GH3 cells exposed to medium with 1,500 μM Ca2+, and release caused by TRH was still 50 and 35% of control in medium with 2.8 and 0.02 μM Ca2+, respectively. Furthermore, TRH transiently increased by 10-fold the fractional efflux of 45Ca2+ from GH3 cells in static incubations with 1,500 or 3.5 μM Ca2+, hereby confirming that the enhanced 45Ca2+ efflux caused by TRH in both low and high Ca2+ medium was not an artifact of the perifusion system.
Annexin-V imaging for noninvasive detection of cardiac allograft rejection
Authors: Jagat Narula, Elmo R. Acio, Navneet Narula, Louis E. Samuels, Billy Fyfe, Diana Wood, Jane M. Fitzpatrick, P.N. Raghunath, John E. Tomaszewski, Christine Kelly, Neil Steinmetz, Allan Green, John F. Tait, Jeffrey Leppo, Francis G. Blankenberg, Diwakar Jain, H. William Strauss
Journal: Nature Medicine (2001)