tbuckley/cabot-search huggingface dataset:
Abstract P363: Circulating Soluble CD163 and Risk of Cardiovascular Disease and All-Cause Mortality in Older Persons: The Cardiovascular Heart Study (CHS)
Authors: Jon P Durda
Journal: Circulation (2015)

Introduction: Macrophages play important roles in atherosclerotic plaque formation and stability. CD163 is a macrophage specific receptor involved in the clearance and endocytosis of hemoglobin-haptoglobin complexes; soluble CD163 (sCD163) may be a useful biomarker to assess macrophage activation. We are not aware of epidemiologic studies of sCD163 levels and cardiovascular disease (CVD) risk. Also it is not known whether common genetic variants are associated with sCD163. Methods: We tested whether sCD163 was associated with carotid intima-media thickness (IMT) and incident clinical events (overall mortality, coronary heart disease [CHD], myocardial infarction [MI], stroke, and congestive heart failure [CHF]) in 4,577 Cardiovascular Health Study (CHS) participants (95% white, 5% black; age range 65-100 y). We used linear regression with adjustment for sex, age, race, study site, current smoking, BMI, hypertension status, systolic blood pressure (SBP) and LDL cholesterol to test for association between sCD163 and IMT. We used 2 Cox proportional hazards models for incident events analyses: (1) adjusting for sex, age, race, study site, and current smoking; (2) model 1 plus BMI, hypertension status, SBP, LDL-cholesterol, C-reactive protein (CRP), interleukin-6 (IL6), and fibrinogen. We also performed a genome-wide association study (GWAS) for sCD163 in 2,769 unrelated CHS white participants, using Hapmap 2 imputed SNPs. Results: sCD163 was positively associated with female sex, white race, age, BMI, SBP, CRP, IL6 and fibrinogen, negatively associated with current smoking status (p&amp;lt0.0001), and not associated with LDL cholesterol or hypertension status. After adjustment for traditional CVD risk factors, sCD163 was positively associated with carotid IMT (p=0.027). In model 1, increased sCD163 levels were associated with overall mortality (p&amp;lt0.0001), incident CHD (p=0.0034), incident stroke (p=0.016), and incident CHF (p&amp;lt0.0001), but not incident MI (p=0.069). None of the model 2 analyses resulted in significant associations (all p&amp;gt0.05). Five variants upstream of chromosome 2q gene MGAT5 (top result rs4954118, p=7.1x10-14) and a single variant (rs314253, p=6.0x10-13) on chromosome 17p between ASGR1 and DLG4 were significantly (p&amp;lt5x10-8) associated with sCD163. The top result near the CD163 gene was for upstream variant rs6488429 (p=8.2x10-5). Conclusions: sCD163 was associated with carotid IMT after accounting for established CVD risk factors. There were associations of sCD163 with mortality and incident clinical CVD, although associations were attenuated after adjustment for other risk factors. Additional studies are needed to evaluate whether results are similar in younger age groups and other populations. The significant results in the GWAS for sCD163 implicate novel molecular pathways that warrant future fine-mapping and functional studies.
Abstract 3572: Endothelin Receptor Inhibitors Decrease Contractility in the Hypertrophied Right Ventricle: Direct Clinical Implications for Patients with Pulmonary Arterial Hypertension
Authors: Jayan Nagendran, Al Haromy, David Z Fu, Kyoko Hashimoto, David B Ross, Ivan M Rebeyka, Evangelos D Michelakis
Journal: Circulation (2008)
Abstract P6-02-07: Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835
Authors: Sergey A Tjulandin, Ilya V Tsimafeyeu, Mikhail Y Byakhov, Wei Yin, John Ludes-Meyers, Frits Daeyaert
Journal: Cancer Research (2015)

Abstract Background: FGFR2 is amplified in 4% of triple-negative breast cancers (TNBC). In addition, the mRNA expression levels of FGFR2 were significantly increased in amplified vs nonamplified tumor samples, suggesting a potential role for FGFR2 in TNBC (Turner et al. 2010). We evaluated efficacy of allosteric inhibition of FGFR2 in high- and low-expressing TNBC xenografts. Methods: Immunocompromised mice were used for xenotransplantation of FGFR2 high-expressing TNBC cells (SUM52PE) or FGFR2 low-expressing TNBC cells (HS578T). Forty animals with measurable tumors were selected on day 10 and randomized into treatment groups (low-molecular weight allosteric inhibitor RPT835, 30 mg/kg; gavage, daily) or vehicle (water; gavage, daily). Measurements of tumor volume (mm3) were performed by digital calipers every 3 days during 40 days after tumor inoculation. Results: RPT835 significantly inhibited aggressive growth of SUM52PE tumor xenograft (P&amp;lt;0.0001). At study day 31, mean tumor volumes (± SE) were 2712.2±37 mm3 in the vehicle group, and 1080.7±49 mm3 in the study group. In addition, animals of the study group received RPT835 from day 31 to day 40 with disease stabilization (no differences in tumor volume between days 31 and 40, P=0.167). The tumor growth curve shows a nearly exponential increase in median tumor volume up to day 31 in the vehicle group and a high rate of slow growing tumors up to day 40 in the study group. In the HS578T xenograft study differences in tumor volume between study and control groups were weak at day 31 (mean tumor volumes ± SE, 703±89.1 mm3 vs. 1053±179.8 mm3, respectively; P&amp;lt;0.001) and at day 40 (1104±162.2 mm3 vs. 1592±335 mm3; P=0.01). Conclusions: The allosteric FGFR2 inhibitor RPT835 significantly impacts on growth of FGFR2-expressing TNBC. Citation Format: Sergey A Tjulandin, Ilya V Tsimafeyeu, Mikhail Y Byakhov, Wei Yin, John Ludes-Meyers, Frits Daeyaert. Targeting triple-negative breast cancer with fibroblast growth factor receptor 2 allosteric inhibitor RPT835 [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-02-07.
How to make foods safer – genetically modified foods
Authors: Bevan E. B. Moseley
Journal: Allergy (2001)

It is the responsibility of companies developing genetically modified foods, and of regulatory authorities that approve their marketing, to ensure that they are at least as safe as the traditional foods they are intended to replace in the diet. This requires that any novel material introduced into the food material should not be allergenic. If the novel gene has come from an allergenic source, e.g. nuts, it is necessary to demonstrate using immunological procedures applied to the IgE fractions of pooled sera from individuals with confirmed allergies that the novel protein is non‐allergenic. When the novel gene is from a non‐allergenic source then it is necessary to demonstrate lack of significant amino acid sequence homology to known allergens together with sensitivity to food manufacturing and digestive processes. Consumer confidence in genetically modified foods would be significantly improved if hypoallergenic varieties of crops and food products that are currently allergenic could be developed. Techniques such as antisense technology and single site amino acid substitution have been shown to have such potential.
Maternal immune status in pregnancy is related to offspring’s immune responses and atopy risk
Authors: G. Herberth, D. Hinz, S. Röder, U. Schlink, U. Sack, U. Diez, M. Borte, I. Lehmann
Journal: Allergy (2011)

To cite this article: Herberth G, Hinz D, Röder S, Schlink U, Sack U, Diez U, Borte M, Lehmann I. Maternal immune status in pregnancy is related to offspring's immune responses and atopy risk. Allergy 2011; 66: 1065–1074. Background: The influence of maternal immune responses in pregnancy on children's immune competence and the development of atopic diseases later in life are poorly understood. To determine potential maternal effects on the maturation of children's immune system and resulting disease risks, we analysed immune responses in mother–child pairs in a prospective birth cohort study. Methods: Within the Lifestyle and Environmental factors and their Influence on Newborns Allergy risk (LINA) study, concentrations of Th1/Th2/Th17 and inflammatory cytokines/chemokines as well as IgE were measured in phytohemagglutinin and lipopolysaccharide stimulated maternal blood in the 34th week of gestation and in corresponding children's blood at birth and 1 year after (n = 353 mother–child pairs). Information on atopic outcomes during the first year of life was obtained from questionnaires. Results: Concentrations of inflammatory markers, excepting TNF-α, were manifold higher in cord blood samples compared with maternal blood. Th1/Th2 cytokines were lower in children's blood with a Th2 bias at birth. Maternal inflammatory parameters (MCP-1, IL-10, TNF-α) in pregnancy showed an association with corresponding cytokines blood levels in children at the age of one. High maternal IgE concentrations in pregnancy were associated with increased children's IgE at birth and at the age of one, whereas children's atopic dermatitis (AD) was determined by maternal AD. Conclusions: Maternal inflammatory cytokines during pregnancy correlate with children's corresponding cytokines at the age of one but are not related to IgE or AD. While maternal IgE predicts children's IgE, AD in children is only associated with maternal disease.
Paradoxical patient reactions to psychiatric life support: clinical and ethical considerations
Authors: S L Pauker, A M Cooper
Journal: American Journal of Psychiatry (1990)

The authors describe cases illustrating two types of high-risk and especially difficult suicidal psychiatric inpatients. In the first case, a suicidal patient reacted to psychiatric life support measures (maximum observation) with increasingly life-threatening acting out, necessitating a difficult, seemingly paradoxical staff decision to withdraw life support. In the second, a patient felt to be improving killed herself when life support was withdrawn. The authors argue that there are clinical limits to psychiatric life support and an appropriate goal of psychiatric treatment is to maximize the chances for patient survival, rather than to attempt to guarantee such survival.
Comparison of Culture-Confirmed Erythema Migrans Caused by Borrelia afzelii in Slovenia
Authors: Franc Strle
Journal: Annals of Internal Medicine (1999)

Background: The clinical manifestations of Lyme borreliosis in North America and Europe seem to differ, but a systematic comparison has never been done. Objective: To compare European and U.S. patients with culture-confirmed erythema migrans. Design: Prospective, clinical cohort study. Setting: University medical centers in Westchester County, New York, and Ljubljana, Slovenia. Patients: 119 U.S. patients with Borrelia burgdorferi sensu stricto infection and 85 Slovenian patients with B. afzelii infection. Measurements: Interview, physical examination, and laboratory assays. Results: Compared with Slovenian patients, U.S. patients had erythema migrans for a briefer duration (median duration, 4 days compared with 14 days; P < 0.001) but were more likely to have systemic symptoms (P = 0.01), abnormal findings on physical examination (P < 0.001), and seroreactivity (P < 0.001). Central clearing of erythema migrans lesions was more likely in Slovenian patients (P < 0.001). Conclusions: Erythema migrans caused by B. afzelii in Slovenia and erythema migrans caused by B. burgdorferi in New York have distinct clinical presentations. Caution should be used when clinical and laboratory experience from one side of the Atlantic is applied to patients on the other.
Correlation of Low CD73 Expression on Synovial Lymphocytes With Reduced Adenosine Generation and Higher Disease Severity in Juvenile Idiopathic Arthritis
Authors: Sophie Botta Gordon‐Smith, Simona Ursu, Simon Eaton, Halima Moncrieffe, Lucy R. Wedderburn
Journal: Arthritis & Rheumatology (2014)

Objective To investigate the expression and adenosine‐generating activity of the ecto‐5′‐nucleotidase CD73 on synovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from children with juvenile idiopathic arthritis (JIA). Methods Given the role of CD73 protein in the production of antiinflammatory adenosine and its intersection with inflammatory biologic pathways, the expression of CD73 on SF and PB lymphocytes from patients with JIA and PB lymphocytes from healthy control subjects was determined by flow cytometry. The AMPase activity of CD73 on PBMCs and SFMCs was measured by high‐performance liquid chromatography. The effects of cell activation on CD73 expression were examined by in vitro culture of PBMCs. Results CD8+ and CD19+ SFMCs from patients with JIA expressed decreased levels of CD73 when compared to paired PBMCs from JIA patients and PBMCs from healthy controls. When the percentages of CD73+ synovial lymphocytes were compared between the 2 clinical forms of oligoarthritis, children with extended oligoarthritis showed lower CD73 expression compared to those with the milder form of the disease. CD8+ SFMCs had a lower ability to produce adenosine from etheno‐AMP compared to CD8+ PBMCs. T cell activation through the T cell receptor (TLR) of CD8+CD73+ cells and B cell activation through TLR‐9 resulted in reduced expression of CD73. This down‐regulation occurred on dividing cells. Conclusion These findings show that low CD73 expression on T and B cells in the inflamed site is related to cell proliferation and is correlated with the clinical severity of oligoarticular JIA. The decreased CD73 expression on SFMCs, in turn, results in reduced adenosine production, which leads to a decreased potential for antiinflammatory activity.
Abstract P382: Continued Thienopyridine Use at Six Months After PCI is Not Associated with Better Outcomes in End-Stage Renal Disease Requiring Dialysis
Authors: Tara I Chang, Maria Montez-Rath, Matthew D Solomon, Jenny Shen, Wolfgang C Winkelmayer
Journal: Circulation (2014)

Introduction: While coronary disease is common in end-stage renal disease, there are few studies of thienopyridine use after PCI in this population. Guidelines recommend 1 to 12 months of thienopyridine use depending on stent type, but are based on patients without advanced kidney disease. However, patients on dialysis often have more severe coronary disease and higher risks of bleeding. We hypothesized that in patients on dialysis undergoing PCI with stenting: 1) most will discontinue thienopyridines prior to 1 year; 2) discontinuation of thienopyridines prior to 6 months post-PCI will associate with higher risks of death or MI, but a lower risk of bleeding. Methods: Using the US Renal Data System, we identified patients on dialysis with Medicare Parts A+B+D (with low-income subsidy) who had PCI with stenting between 7/07 and 12/09. Thienopyridine discontinuation was defined as &gt;30-day gap in supply. We performed a landmark analysis, selecting patients who were event-free at 6 months after PCI, and categorized them as having discontinued thienopyridines or not at that point. We propensity-matched patients for discontinued vs. continued use and fit Cox models to examine death, death or MI, and hospitalized bleeding. Results: We identified 4686 patients, 66% of whom received a drug-eluting stent [DES]. At 90-days, 78% of DES and 65% of bare metal stent (BMS) patients used a thienopyridine; this proportion fell to 64% and 48% at 6 months, and 42% and 29% at 1 year. Overall rates of death and MI were high (Table). In the matched cohorts, patients who discontinued thienopyridine use prior to 6 months (vs. continued use) had no significant differences in long-term outcomes (Table). Conclusions: In patients on dialysis who undergo PCI with stenting, most use thienopyridines for &lt;1 year. Continued thienopyridine use at 6 months was not associated with a significant benefit or with higher bleeding risk. Our study highlights the need for future trials to determine the optimal duration of thienopyridine use after PCI in this high-risk population.
Severe Acne in Female-to-Male Transgender Patients
Authors: Lucia Turrion-Merino, Marta Urech-García-de-la-Vega, Laura Miguel-Gomez, Antonio Harto-Castaño, Pedro Jaen-Olasolo
Journal: JAMA Dermatology (2015)

and grains, hyperkeratosis, and parakeratosis.Both present clinically with hyperkeratotic papules and warty plaques but differ in their age of onset and associated abnormalities.ADEN is often congenital, while DD typically manifests in the second or third decade of life.Typically, DD has associated nail abnormalities, mucous membrane involvement, palmoplantar pits, and punctate keratoses, while ADEN does not. 2 Genetic testing is available, as is immunohistochemical staining of tissue for SERCA2 protein expression.The genetic difference between the 2 disorders remains controversial.Darier disease is caused by mutations in ATP2A2, which encodes the SERCA2 pump.Mutations of SERCA2 have been discovered in at least 2 patients with ADEN, leading some clinicians to classify ADEN as segmental DD resulting from postzygotic mosaicism. 3Others maintain that congenital or early childhood onset and linear distribution suggest ADEN and not segmental DD. 4 There is 1 reported case of ADEN where lack of ATP2A2 mutation was confirmed by DNA analysis. 5n our patient, IHC staining identified SERCA2 protein in lesional skin.However, the IHC staining does not substantiate normal function of the protein.Genetic testing was not economically feasible for this family but may be appropriate when a patient desires genetic counseling, prenatal diagnosis, or identification of at-risk family members.The Genetic Testing Registry lists several laboratories that will perform sequence analysis of the ATP2A2 gene. 6With 96% specificity, the lack of ATP2A2 gene mutation nearly excludes a diagnosis of DD.Our case supports the premise that ADEN has clinical and prognostic features distinct from DD despite their overlapping histopathologic findings.Although IHC staining of SERCA2 can be helpful, further study of genotype-phenotype correlations may allow better distinction of these 2 clinical entities.
A CASE PRESENTING PULMONARY AND OSSEOUS LESIONS PRESUMABLY DUE TO SARCOID
Authors: Henry F. Stoll
Journal: Annals of Internal Medicine (1937)

Case Reports1 April 1937A CASE PRESENTING PULMONARY AND OSSEOUS LESIONS PRESUMABLY DUE TO SARCOIDHENRY F. STOLL, M.D., F.A.C.P.HENRY F. STOLL, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-10-10-1588 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptExcept among dermatologists, whose chief interest is confined to the skin manifestations, one rarely hears of sarcoid. The fact that there may be extensive involvement of the viscera and bones in addition to skin lesions appears to be quite generally unknown among internists though such cases were described over 20 years ago. When the skin manifestations are slight or even absent and the other lesions pronounced, a difficult diagnostic problem is presented as the case here reported illustrates.CASE REPORTW. C., aged 14 years, was referred to me January 16, 1929, for examination because of cough. His general health...References1. HUNTER FT: Hutchinson-Boeck's disease (generalized "sarcoidosis"); historical note and report of case with apparent cure, New Eng. Jr. Med., 1936, ccxiv, 346-352. CrossrefGoogle Scholar2. KIENBOCK R: Quoted by Hunter in his bibliography.1 Google Scholar3. KUGNITSKYBITTORF : Quoted by Hunter in his bibliography.1 Google Scholar4. GOECKERMAN WH: Sarcoids and related lesions; report of 17 cases; review of recent literature, Arch. Dermat. and Syph., 1928, xviii, 237-262. CrossrefGoogle Scholar5. SULZBERGER MB: Sarcoid of Boeck (benign miliary lupoid) and tuberculin anergy; report of case and general remarks, Am. Rev. Tuberc., 1933, xxviii, 734-745. Google Scholar6. NIELSEN J: Recherches radiologiques sur les lésions des os et des poumons dans les sarcoïdes de Boeck, Bull. Soc. franç. de dermat. et syph. (Réunion dermat., Strasbourg), 1934, xli, 1187-1218. Google Scholar7. PIÉRARD J: Le granulome annulaire doit-il être rangé parmi les sarcoïdes de Boeck? Bull. Soc. franç. de dermat. et syph. (Réunion dermat., Strasbourg), 1934, xli, 1275-1278. Google Scholar8. KISSMEYER A: La maladie de Boeck; Sarcoïdes cutanées bénignes multiples, 1932, Levin and Munksgaard, Copenhagen, Denmark. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Hartford, Connecticut*Presented at the Detroit meeting of the American College of Physicians, March 5, 1936.†Deceased. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1937Volume 10, Issue 10Page: 1588-1594KeywordsBoneLesions ePublished: 1 December 2008 Issue Published: 1 April 1937 PDF downloadLoading ...
Efflux of Rhodamine From CD56+ Cells as a Surrogate Marker for Reversal of P-Glycoprotein–Mediated Drug Efflux by PSC 833
Authors: Robert Robey, Susan Bakke, Wilfred Stein, Beverly Meadows, Thomas Litman, Sheela Patil, Tom Smith, Tito Fojo, Susan Bates
Journal: Blood (1999)
Weapons of War
Authors: Rebecca Voelker
Journal: JAMA (1999)

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