tbuckley/cabot-search huggingface dataset:
α-Type-1 Polarized Dendritic Cells
Authors: Robbie B. Mailliard, Anna Wankowicz-Kalinska, Quan Cai, Amy Wesa, Catharien M. Hilkens, Martien L. Kapsenberg, John M. Kirkwood, Walter J. Storkus, Pawel Kalinski
Journal: Cancer Research (2004)

Abstract Using the principle of functional polarization of dendritic cells (DCs), we have developed a novel protocol to generate human DCs combining the three features critical for the induction of type-1 immunity: (a) fully mature status; (b) responsiveness to secondary lymphoid organ chemokines; and (c) high interleukin-12p70 (IL-12p70)-producing ability. We show that IFN-α and polyinosinic:polycytidylic acid (p-I:C) synergize with the “classical” type-1-polarizing cytokine cocktail [tumor necrosis factor α (TNFα)/IL-1β/IFNγ], allowing for serum-free generation of fully mature type-1-polarized DCs (DC1). Such “α-type-1-polarized DC(s)” (αDC1) show high migratory responses to the CCR7 ligand, 6C-kine but produce much higher levels of IL-12p70 as compared to TNFα/IL-1β/IL-6/prostaglandin E2 (PGE2)-matured DCs (sDC), the current “gold standard” in DC-based cancer vaccination. A single round of in vitro sensitization with αDC1 (versus sDCs) induces up to 40-fold higher numbers of long-lived CTLs against melanoma-associated antigens: MART-1, gp100, and tyrosinase. Serum-free generation of αDC1 allows, for the first time, the clinical application of DCs that combine the key three features important for their efficacy as anticancer vaccines.
The ‘melanocyte-keratin’ mystery revisited: neither normal human epidermal nor hair follicle melanocytes express keratin 16 or keratin 6<i>in situ</i>
Authors: Y. Ramot, E. Gáspár, A. Dendorfer, L. Langbein, R. Paus
Journal: British Journal of Dermatology (2009)

Keratin family proteins are generally accepted as being restricted to epithelial cells. However, several studies have challenged this paradigm by reporting, for example, that melanoma cells can express keratins and that normal human epidermal melanocytes, which derive from the neural crest, express keratin 16 (K16) in situ.We wished to confirm or refute that K16 and/or its intermediate filament partner, keratin 6 (K6), are expressed in normal human epidermal and/or hair follicle melanocytes in situ.Cryosections of normal human scalp skin were subjected to highly sensitive double immunohistochemistry with specific antibodies against K16 or K6 and against the melanocyte-specific marker NKI/beteb (gp100). Immunoreactivity (IR) was visualized by conventional light microscopy and confocal fluorescence microscopy.Despite the use of different, high-sensitivity immunostaining methods, stringent positive and negative controls, and monospecific, well-characterized antikeratin antibodies, we could detect neither K16 nor K6 IR within intraepidermal or intrafollicular pigment cells of normal human scalp skin. Instead, NKI/beteb+ cells were found to be intimately embedded in foci of K16+ and/or K6+ keratinocytes, which might create the illusion of keratin expression by these cells.Human epidermal or hair follicle melanocytes do not express K16 and/or K6 while residing in their natural habitat.
Dominant gain-of-function STAT1 mutations in FOXP3 wild-type immune dysregulation–polyendocrinopathy–enteropathy–X-linked–like syndrome
Authors: Gulbu Uzel, Elizabeth P. Sampaio, Monica G. Lawrence, Amy P. Hsu, Mary Hackett, Morna J. Dorsey, Richard J. Noel, James W. Verbsky, Alexandra F. Freeman, Erin Janssen, Francisco A. Bonilla, Joseph Pechacek, Prabha Chandrasekaran, Sarah K. Browne, Anahita Agharahimi, Ahmed M. Gharib, Sara C. Mannurita, Jae Joon Yim, Eleonora Gambineri, Troy Torgerson, Dat Q. Tran, Joshua D. Milner, Steven M. Holland
Journal: Journal of Allergy and Clinical Immunology (2013)
Cardiovascular side effects of cancer therapies: a position statement from the Heart Failure Association of the European Society of Cardiology
Authors: Thomas Eschenhagen, Thomas Force, Michael S. Ewer, Gilles W. de Keulenaer, Thomas M. Suter, Stefan D. Anker, Metin Avkiran, Evandro de Azambuja, Jean‐Luc Balligand, Dirk L. Brutsaert, Gianluigi Condorelli, Arne Hansen, Stephane Heymans, Joseph A. Hill, Emilio Hirsch, Denise Hilfiker‐Kleiner, Stefan Janssens, Steven de Jong, Gitte Neubauer, Burkert Pieske, Piotr Ponikowski, Munir Pirmohamed, Mathias Rauchhaus, Douglas Sawyer, Peter H. Sugden, Johann Wojta, Faiez Zannad, Ajay M. Shah
Journal: European Journal of Heart Failure (2010)
Like-Triple Diabetes as First Manifestation of MODY2 in an Overweight Teenager With Transient Multiple Antibodies
Authors: Anna Wędrychowicz, Małgorzata Stelmach, Krystyna Wyka, Jerzy Starzyk
Journal: Diabetes Care (2014)

Patients with heterozygous inactivating mutations in the gene encoding glucokinase, which causes type 2 maturity-onset diabetes of the young (MODY2), have mild fasting hyperglycemia that usually remains considerably stable during life and requires only diabetic diet as treatment. Atypical course of disease is uncommon.

An 11-year-old, prepubertal, Caucasian overweight boy (BMI 22.5 kg/m2) with gynecomastia/steatomastia and diabetes was diagnosed on the basis of an oral glucose tolerance test without any typical symptoms (2-h blood glucose 215 mg/dL). Insulin levels were quite high (fasting 17.1 IU/mL, 2-h 114 IU/mL). Since 6 years of age he had been treated for Asperger syndrome, currently with risperidone. His family history was positive for diabetes in the previous three generations. At the time of diabetes diagnosis, dyslipidemia with elevated total cholesterol (212 mg/dL), triglycerides (150 mg/dL), and LDL cholesterol (133.1 mg/dL) was observed. Diabetes autoantibodies were significantly positive: islet antigen 2 antibodies …
Adjunctive biomarkers for improving diagnosis of tuberculosis and monitoring therapeutic effects
Authors: Yun-Gyoung Hur, Young Ae Kang, Sun-Hee Jang, Ji Young Hong, Ahreum Kim, Sang A Lee, Youngmi Kim, Sang-Nae Cho
Journal: Journal of Infection (2014)

To identify host biomarkers associated with latent tuberculosis infection (LTBI), active tuberculosis (TB), and nontuberculous mycobacteria (NTM) diseases to improve diagnosis and effective anti-TB treatment.Active TB and NTM patients at diagnosis, recent TB contacts, and normal healthy subjects were recruited. Tuberculin skin tests, QuantiFERON-TB Gold In-Tube tests, and multiplex bead arrays with 17 analytes were performed. TB patients were re-evaluated after 2 and 6 months of treatment.Mycobacterium tuberculosis (M. tb) antigen-specific IFN-γ, IL-2, and CXCL10 responses were significantly higher in active TB and LTBI compared with controls (P < 0.01). Only serum VEGF levels varied between the active TB and LTBI groups (AUC = 0.7576, P < 0.001). Active TB and NTM diseases were differentiated by serum IL-2, IL-9, IL-13, IL-17, TNF-α and sCD40L levels (P < 0.05). Increased sCD40L and decreased M. tb antigen-specific IFN-γ levels correlated with sputum clearance of M. tb after 2 months of treatment (P < 0.001).Serum IL-2, IL-9, IL-13, IL-17, TNF-α, sCD40L and VEGF-A levels may be adjunctive biomarkers for differential diagnosis of active TB, LTBI, and NTM disease. Assessment of serum sCD40L and M. tb antigen-specific IFN-γ, TNF-α, and IL-2 levels could help predict successful anti-TB treatment in conjunction with M. tb clearance.
Hypocapnia and measurement of airflow resistance and dynamic compliance as functions of respiratory frequency.
Authors: A Cutillo, A H Bigler, R Perondi, M Turiel, S Watanabe, A D Renzetti
Journal: Thorax (1982)

Measurements of lung mechanical behaviour as a function of respiratory frequency may be associated with significantly increased ventilation at high breathing rates. It follows that these measurements may be influenced by hypocapnia which has been shown to increase airflow resistance and to decrease dynamic compliance. To examine this possibility we continuously monitored the end-tidal CO2 tension during the determination of pulmonary resistance and dynamic compliance as functions of frequency and we compared measurements obtained by the standard method and by a technique designed to prevent the development of hypocapnia at high breathing rates. We studied 11 patients with chronic obstructive pulmonary disease and also two smokers with normal spirometry and resistance. Although conventional measurements at frequencies higher than 40-45 breaths/min were associated with a significant decrease in end-tidal CO2, no systematic differences were found between the values of pulmonary resistance and dynamic compliance obtained by the two techniques. Our data indicate that the development of hypocapnia at high breathing rates does not significantly affect measurements of resistance and compliance as functions of frequency, at least when the duration of each period of hyperventilation is limited to the minimum necessary for a single determination, which was less than 30 seconds in the present study. A comparison of our results with previously published data suggests that the time factor may be critical with respect to the possible effects of hypocapnia on these measurements.
Factors Associated With Spontaneous Transformation of Hamster Cells in Culture&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Avraham Yaniv, Tamar Gotlieb-Stematsky
Journal: JNCI Journal of the National Cancer Institute (1970)

Spontaneously transformed cells in primary hamster-embryo cultures were assayed. Dispersed cells yielded a high percentage of spontaneous, morphologically transformed colonies from the total number of colonies formed. Transformed colonies remained at about the same rate when primary cultures containing transformed cells were passaged, whereas cultures that did not contain transformed cells produced no such colonies when passaged. Embryos of different ages and various embryo organs used as the source of cell cultures failed to yield a higher percentage of transformed colonies. Only cultures of embryo lung produced higher rates of transformed colonies. Horse serum promoted the growth of fibroblast-type cells oriented in parallel arrangement, whereas calf serum inhibited cells of this type. The presence of cells with abnormal chromosomes even in the primary cultures, and particularly in embryo lung tissues, may account for the transformed cells. Also the change of chromosomes from diploid to heteroploid occurred rapidly in the transformed clones after culture in vitro. Cell lines obtained from cloned primary cultures produced tumors in hamsters after short latent periods and with fewer cells than cell lines obtained from uncloned cultures. The cloned cell lines also had generation times and growth potential in vitro that correlated with transplantability in vivo. In one cloned cell line, there was a marked discrepancy between morphological transformation and tumorigenicity.
Results of prospective randomized study of local enoxaparin delivery versus systemic heparinization for NIR stent placement
Authors: R.S. Kiesz, E. Deutsch, P. Buszman, J. Martin, M.M. Rozek, M. Rewick, P. Seweryniak, M. Kusmider, M. Tendera
Journal: Journal of the American College of Cardiology (1998)
A randomised trial of a brace for patellofemoral osteoarthritis targeting knee pain and bone marrow lesions
Authors: Michael J Callaghan, Matthew J Parkes, Charles E Hutchinson, Andrew D Gait, Laura M Forsythe, Elizabeth J Marjanovic, Mark Lunt, David T Felson
Journal: Annals of the Rheumatic Diseases (2015)

Objective Braces used to treat (PF) osteoarthritis (OA) may reduce contact stress across the PF joint. We hypothesised that in PF OA, braces would decrease knee pain and shrink PF bone marrow lesions (BMLs). Methods Eligible subjects had painful PF OA. Subjects were randomly allocated to brace or no brace for 6 weeks. Knee MRIs were acquired at baseline and 6 weeks. We measured BMLs on post-contrast fat suppressed sagittal and proton density weighted axial images. The primary symptom outcome was change in pain at 6 weeks during a preselected painful activity, and the primary structural outcome was BML volume change in the PF joint. Analyses used multiple linear regression. Results We randomised 126 subjects aged 40–70 years (mean age 55.5 years; 72 females (57.1%)). Mean nominated visual analogue scale (0–10 cm) pain score at baseline was 6.5 cm. 94 knees (75%) had PF BMLs at baseline. Subjects wore the brace for a mean of 7.4 h/day. 6 subjects withdrew during the trial. After accounting for baseline values, the brace group had lower knee pain than the control group at 6 weeks (difference between groups −1.3 cm, 95% CI −2.0 to −0.7; p&lt;0.001) and reduced PF BML volume (difference −490.6 mm 3 , 95% CI −929.5 to −51.7; p=0.03) but not tibiofemoral volume (difference −53.9 mm 3 , 95% CI −625.9 to 518.2; p=0.85). Conclusions A PF brace reduces BML volume in the targeted compartment of the knee, and relieves knee pain. Trial registration number UK. ISRCTN50380458 .
Combination Anastrozole and Fulvestrant in Metastatic Breast Cancer
Authors: Rita S. Mehta, William E. Barlow, Kathy S. Albain, Ted A. Vandenberg, Shaker R. Dakhil, Nagendra R. Tirumali, Danika L. Lew, Daniel F. Hayes, Julie R. Gralow, Robert B. Livingston, Gabriel N. Hortobagyi
Journal: New England Journal of Medicine (2012)

The aromatase inhibitor anastrozole inhibits estrogen synthesis. Fulvestrant binds and accelerates degradation of estrogen receptors. We hypothesized that these two agents in combination might be more effective than anastrozole alone in patients with hormone-receptor (HR)-positive metastatic breast cancer.
Sulphasalazine inhibits human antigen-specific immune responses in vivo
Authors: C. Trollmo, S. Gudmundsson, N. Feltelius, S. Rogberg, G. Smedegard, L. Klareskog
Journal: Annals of the Rheumatic Diseases (2006)

<b>Objective:</b> To study the effects of the antirheumatic drug sulphasalazine (SASP) on the immune system by analysing systemic and gut-associated immune responses. <b>Methods:</b> A total of 23 healthy volunteers were treated with either SASP or placebo for 5 weeks in a double-blind fashion and immunised 2 weeks after the initiation of treatment. Specific immune responses were triggered by subcutaneous immunisation with tetanus toxoid and by peroral immunisation with inactivated influenza vaccine. The effects of treatment on specific immunity to tetanus and influenza were evaluated by enzyme-linked immunospot assay quantifying the number of circulating specific and total antibody-producing cells (spot-forming cells (SFC)) at 6, 8 and 10 days after immunisation. <b>Results:</b> An immunosuppressive effect of SASP on systemic immune response was observed with a decrease in the total number of IgG-SFC, IgG anti-tetanus SFC and IgG anti-tetanus antibody levels in serum. SASP also exerted an immunosuppressive effect on the mucosa-associated immune system as seen from its down-regulating effect on the total number of circulating IgA SFC. <b>Conclusions:</b> These data show firstly that SASP exerts an immunosuppressive effect on defined immune responses to immunisation in vivo, and secondly that both mucosa-associated and systemic immunity are affected by SASP treatment.
Prognostic Significance of <i>CEBPA</i> Mutations in a Large Cohort of Younger Adult Patients With Acute Myeloid Leukemia: Impact of Double <i>CEBPA</i> Mutations and the Interaction With <i>FLT3</i> and <i>NPM1</i> Mutations
Authors: Claire L. Green, Kenneth K. Koo, Robert K. Hills, Alan K. Burnett, David C. Linch, Rosemary E. Gale
Journal: Journal of Clinical Oncology (2010)

Purpose To determine the clinical relevance of mutations in the CCAAT/enhancer binding protein α (CEBPA) gene in acute myeloid leukemia (AML) and to examine factors that might modify prognostic impact. Patients and Methods The entire CEBPA coding sequence was screened in 1,427 young adult patients with AML, excluding acute promyelocytic leukemia, using denaturing high-performance liquid chromatography and direct sequencing. Results Of 107 patients (7%) with CEBPA mutations, 48 patients (45%) had one mutation (CEBPA-single), and 59 patients (55%) had two mutations (CEBPA-double). The incidence of CEBPA-double patients was similar in intermediate cytogenetic risk patients with and without a normal karyotype (6% and 5%, respectively). CEBPA-double patients had evidence of a lower coincidence with FLT3/ITDs (P = .04) and were highly unlikely to have an NPM1 mutation (P &lt; .0001). CEBPA-double but not CEBPA-single patients had a significantly better overall survival (OS) at 8 years (34%, 31%, and 54% for CEBPA–wild-type [WT], CEBPA-single, and CEBPA-double, respectively, P = .004). This benefit was lost in the presence of a FLT3/ITD (OS for CEBPA-WT, CEBPA-single, and CEBPA-double FLT3/ITD-negative patients: 36%, 35%, 59%, respectively, P = .002; OS for CEBPA-WT, CEBPA-single, and CEBPA-double FLT3/ITD-positive patients: 26%, 21%, 14%, respectively, P = .05). There was no evidence of any additional favorable benefit for a CEBPA-single mutation in the presence of an NPM1 mutation (OS, 45%, 44%, and 56%, P = .2, for NPM1-positive/CEBPA-WT, NPM1-positive/CEBPA-single, and NPM1-negative/CEBPA-double patients, respectively). Conclusion Screening for CEBPA mutations can be restricted to patients with intermediate-risk cytogenetics lacking an FLT3/ITD or NPM1 mutation. Only the presence of a CEBPA-double mutation should be used for therapy risk stratification.
Association of Incident Cardiovascular Disease With Periodic Limb Movements During Sleep in Older Men
Authors: Brian B. Koo, Terri Blackwell, Sonia Ancoli-Israel, Katie L. Stone, Marcia L. Stefanick, Susan Redline
Journal: Circulation (2011)

Periodic limb movements during sleep (PLMS) cause repetitive sympathetic activation and may be associated with increased cardiovascular risk. We hypothesized that PLMS frequency (periodic limb movement index [PLMI]) and PLMS arousal frequency (periodic limb movement arousal index [PLMAI]) are predictive of incident cardiovascular disease, including coronary heart disease, peripheral arterial disease, and cerebrovascular disease, in an elderly male cohort.
Accuracy of pulse oximeters in estimating heart rate at rest and during exercise.
Authors: Y Iyriboz, S Powers, J Morrow, D Ayers, G Landry
Journal: British Journal of Sports Medicine (1991)

Pulse oximeters are being widely used for non-invasive, simultaneous assessment of haemoglobin oxygen saturation. They are reliable, accurate, relatively inexpensive and portable. Pulse oximeters are often used for estimating heart rate at rest and during exercise. However, at present the data available to validate their use as heart rate monitors are not sufficient. We evaluated the accuracy of two oximeters (Radiometer, ear and finger probe; Ohmeda 3700, ear probe) in monitoring heart rate during incremental exercise by comparing the pulse oximeters with simultaneous ECG readings. Data were collected on eight men (713 heart rate readings) during graded cycle ergometer and treadmill exercise to volitional fatigue. Analysis by linear regression revealed that general oximeter readings significantly correlated with those of ECG (r = 0.91, P less than 0.0001). However, comparison of heart rate at each level of work showed that oximeter readings significantly (P less than 0.05) under-estimated rates above 155 beats/min. These results indicate that the use of pulse oximeters as heart rate monitors during strenuous exercise is questionable. This inaccuracy may well originate from the instability of the probes, sweating, other artefacts during exercise, and measurement of different components in the cardiovascular cycle.
Responsiveness and interpretation of a symptom severity index specific to upper gastrointestinal disorders
Authors: Dennis A. Revicki, Anne M. Rentz, Jan Tack, Vincenzo Stanghellini, Nicholas J. Talley, Peter Kahrilas, Christine de la Loge, Elyse Trudeau, Dominique Dubois
Journal: Clinical Gastroenterology and Hepatology (2004)
Occurrence and relative risk of stroke in incident and prevalent contemporary rheumatoid arthritis
Authors: Marie Holmqvist, Emma Gränsmark, Ängla Mantel, Lars Alfredsson, Lennart T H Jacobsson, Solveig Wallberg-Jonsson, Johan Askling
Journal: Annals of the Rheumatic Diseases (2012)

In contrast with the wealth of data on ischaemic heart disease in rheumatoid arthritis (RA), data on stroke are scarce and contradictory. Despite the high clinical and aetiological relevance, there is no data regarding when (if ever) after RA diagnosis there is an increased risk. Our objective was to assess the risk of stroke (by subtype) in contemporary patients with RA, particularly in relation to time since RA diagnosis.One incident RA cohort diagnosed between 1997 and 2009 (n=8077) and one nationwide prevalent RA cohort followed at Swedish rheumatology clinics between 2005 and 2009 ((n=39 065) were assembled). Each cohort member was matched to a general population comparator. Information on first-time hospitalisations for stroke up to 2009 was retrieved from the Swedish Patient Register. HR and 95% CI were estimated using Cox models.In prevalent unselected RA, the HR of ischaemic stroke was 1.29 (95% CI 1.18 to 1.41). In the incident RA cohort, the overall risk increase was small and non-significant (overall HR 1.11, 95% CI 0.95 to 1.30). When stratified by RA disease duration, an increased risk of ischaemic stroke was indeed detectable but only after 10 or more years since RA diagnosis (HR>10 years: 2.33, 95% CI 1.25 to 4.34). Risk of haemorrhagic stroke was increased in prevalent but not in incident RA.The magnitude of stroke risk is lower than for ischaemic heart disease in RA, and the evolvement of this risk from RA diagnosis may be slower. This suggests different driving forces behind these two RA co-morbidities and has implications for the clinical follow-up of patients with RA.
Quality control of equipment in home mechanical ventilation: a European survey
Authors: R. Farre
Journal: European Respiratory Journal (2005)

Quality control of the equipment used in home mechanical ventilation is necessary in order to ensure that patients safely and accurately receive the prescribed ventilatory support. The aim of this study was to carry out a survey on the quality-control procedures in different centres and countries. The survey was carried out in the context of a European Commission Concerted Action covering 16 European countries. The study was extensive and detailed, involving 326 centres, which provided home ventilation to &gt;20,000 patients. The survey showed that: 1) ventilator servicing was mainly carried out by external companies (62% of centres), with a servicing frequency ranging 3–12 months; 2) interaction between servicing companies and prescribers was limited (only 61% of centres were always informed of major incidents); 3) participation of centres in equipment quality control was poor (only 56% of centres assessed that patients/caregivers correctly cleaned/maintained the ventilator); and 4) centres were insufficiently aware of vigilance systems (only 23% of centres). Moreover, the data showed considerable inter- and intra-country differences. The size of the centre was an important determinant of many of these quality-control aspects. This survey provides information that will enable the European Commission Concerted Action to formulate recommendations on procedures for home-ventilator quality control.
Heterogeneous gap junction remodeling in reentrant circuits in the epicardial border zone of the healing canine infarct☆
Authors: C CABO, J YAO, P BOYDEN, S CHEN, W HUSSAIN, H DUFFY, E CIACCIO, N PETERS, A WIT
Journal: Cardiovascular Research (2006)

Background: The epicardial border zone (EBZ) of surviving myocytes in the healing, 4- to 5-day-old canine infarct is an arrhythmogenic substrate characterized by both structural and functional remodeling of Cx43. Unknown is whether the remodeling of gap junction conductance is heterogeneous in the EBZ like that of sarcolemmal ion channel remodeling and how remodeling of the gap junction influences conduction and anisotropy.