tbuckley/cabot-search huggingface dataset:
In vitro molecular interactions and distribution of KCNE family with KCNQ1 in the human heart
Authors: S BENDAHHOU, C MARIONNEAU, K HAUROGNE, M LARROQUE, R DERAND, V SZUTS, D ESCANDE, S DEMOLOMBE, J BARHANIN
Journal: Cardiovascular Research (2005)

The voltage-gated K+ channel KCNQ1 associates with the small KCNE1 beta subunit to underlie the IKs repolarizing current in the heart. Based on sequence homology, the KCNE family is recognized to comprise five members. Controversial data have indicated their participation in several K+ channel protein complexes, including KCNQ1. The expression level and the putative functions of the different KCNE subunits in the human heart still require further investigation.We have carried out a comparative study of all KCNE subunits with KCNQ1 using the patch-clamp technique in mammalian cells. Real-time RT-PCR absolute quantification was performed on human atrial and ventricular tissue.While KCNQ1/KCNE1 heteromultimer reached high current density with slow gating kinetics and pronounced voltage dependence, KCNQ1/KCNE2 and KCNQ1/KCNE3 complexes produced instantaneous voltage-independent currents with low and high current density, respectively. Co-expression of KCNE4 or KCNE5 with KCNQ1 induced small currents in the physiological range of voltages, with kinetics similar to those of the KCNQ1/KCNE1 complex. However, co-expression of these inhibitory subunits with a disease-associated mutation (S140G-KCNQ1) led to currents that were almost undistinguishable from the KCNQ1/KCNE1 canonical complex. Absolute cDNA quantification revealed a relatively homogeneous distribution of each transcript, except for KCNE4, inside left atria and endo- and epicardia of left ventricular wall with the following abundance: KCNQ1 >> KCNE4 > or = KCNE1 > KCNE3 > KCNE2 > KCNE5. KCNE4 expression was twice as high in atrium compared to ventricle.Our data show that KCNQ1 forms a channel complex with 5 KCNE subunits in a specific manner but only interactions with KCNE1, KCNE2, and KCNE3 may have physiological relevance in the human heart.
Continuous Quality Improvement in the Cardiac Catheterization Laboratory
Authors: Ralph G. Brindis, Gregory J. Dehmer
Journal: Circulation (2006)

ontinuous quality improvement (CQI) has been described as a methodology to continually improve the processes associated with providing a product or service to meet or exceed customer expectations. 1In reality, the CQI process is a collection of techniques borrowed from the fields of systems theory, statistics, engineering, psychology, and others and is based on the work of pioneers in industrial management such as Deming and Juran. 2 As a management philosophy, CQI is an organized, scientific process for evaluating, planning, improving, and controlling quality.Simply stated, the goal of CQI is to reduce variation and improve overall performance.Positive experiences in other industries lead to the application of CQI methods in healthcare in the hope that reduced variation and better performance would improve patient outcomes and result in cost savings.This is fundamentally different than the earlier quality assurance (QA) process used in healthcare, which was geared to identify and eliminate "low-end performers or outliers," leaving only the acceptable performers.The CQI approach in healthcare has been promoted by individuals such as Donabedian, 3 Berwick et al, 4 and Jencks and Wilensky. 5It builds on traditional QA methods to develop programs that will reduce variation and improve overall performance.
Storage mite allergy among bakers
Authors: P. Revsbech, M. Dueholm
Journal: Allergy (1990)

Allergy to storage mites has been shown among farmers and grain elevator workers. This study aimed to examine whether bakers also are sensitized to storage mites. Twenty‐three bakers or other employees in bakeries suffering from nasal or pulmonary symptoms were compared with 17 control persons with no relation to bakery work or agriculture. All participants underwent skin prick test with a standard panel of allergens, four types of flour and the storage mites Acarus sin, Lepidoglyphus destructor and Tyrophagus putrescentiae , RAST to storage mites and flour, and measurement of total IgE. We found no difference between the baker group and the control group in prevalence and strength of positive skin prick test or RAST to any of the three storage mite species. In the baker group positive RAST to flour was related to positive RAST to A. siro and L. destructor , but not T. putrescentiae. Almost all bakers sensitized to flour were also sensitized to storage mites (6 of 7). We suggest that if a baker become sensitized to flour he will be more prone to develop specific IgE towards storage mites too.
Extended Dose Ipilimumab with a Peptide Vaccine: Immune Correlates Associated with Clinical Benefit in Patients with Resected High-Risk Stage IIIc/IV Melanoma
Authors: Amod A. Sarnaik, Bin Yu, Daohai Yu, Dawn Morelli, MacLean Hall, Dilip Bogle, Lulu Yan, Stephan Targan, Jolie Solomon, Geoff Nichol, Michael Yellin, Jeffrey S. Weber
Journal: Clinical Cancer Research (2010)

To determine safety and feasibility of adjuvant ipilimumab following resection of high-risk melanoma and to identify surrogate markers for benefit.In this phase II trial, 75 patients with resected stage IIIc/IV melanoma received the CTLA-4 antibody ipilimumab every 6 to 8 weeks for 1 year. Eligible patients received further maintenance treatments. The first 25 patients received 3 mg/kg of ipilimumab, and an additional 50 patients received 10 mg/kg. HLA-A*0201+ patients received multipeptide immunizations in combination with ipilimumab. Leukapheresis was performed prior to and 6 months after initiation of treatment.Median overall and relapse-free survivals were not reached after a median follow-up of 29.5 months. Significant immune-related adverse events were observed in 28 of 75 patients and were positively associated with longer relapse-free survival. Antigen-specific T cell responses to vaccine were variable, and vaccine combination was not associated with additional benefit. No effects on T regulatory cells were observed. Higher changes in Th-17 inducible frequency were a surrogate marker of freedom from relapse (P = 0.047), and higher baseline C-reactive protein (CRP) levels were associated with freedom from relapse (P = 0.035).Adjuvant ipilimumab following resection of melanoma at high risk for relapse appeared to be associated with improved outcome compared to historical reports. Significant immune-related adverse events were generally reversible and appeared to be associated with improved relapse-free survival. Although vaccination failed to induce a consistent in vitro measurable response, a higher change in Th-17 inducible cells and higher baseline CRP levels were positively associated with freedom from relapse.
Gefitinib (ZD1839) Monotherapy as a Salvage Regimen for Previously Treated Advanced Non-Small Cell Lung Cancer
Authors: Jinny Park, Byung Bae Park, Jee Youn Kim, Se-Hoon Lee, Soon Il Lee, Ho Young Kim, Jung Han Kim, Se Hoon Park, Kyung-Eun Lee, Joon Oh Park, Kihyun Kim, Chul Won Jung, Young Suk Park, Young-Hyuck Im, Won Ki Kang, Mark H. Lee, Keunchil Park
Journal: Clinical Cancer Research (2004)

Abstract Purpose: A worldwide compassionate-use program has enabled &amp;gt;42,000 patients with advanced non-small cell lung cancer (NSCLC) to receive gefitinib treatment. Here we report the outcome of gefitinib therapy in patients who enrolled in the “Iressa” Expanded Access Program at the Samsung Medical Center. Experimental Design: Patients with advanced or metastatic NSCLC who had progressed after prior systemic chemotherapy and for whom no other treatment option was available were eligible to receive gefitinib treatment as part of the Expanded Access Program. A post hoc assessment of potential prognostic factors for response and survival was performed by multivariate analysis. Results: All 111 evaluable patients had stage IV disease; most patients had a baseline performance status of 2 [n = 52 (47%)] or 3 [n = 18 (16%)] and had received ≥2 prior chemotherapy regimens (56%). The objective response rate was 26%, the disease control rate (measured over ≥8 weeks) was 40%, and the 1-year survival rate was 44%. Adenocarcinoma histology was associated with better response and disease control rates, and a performance status of 0–2 was also associated with a better disease control rate. Both of these factors, as well as female gender, were significantly associated with longer survival. Gefitinib was well tolerated; the most common adverse event was grade 1 skin rash. Conclusions: Gefitinib demonstrated significant antitumor activity and a favorable tolerability profile in this series of NSCLC patients with poor prognosis.
Restoration of Norepinephrine-Modulated Contextual Memory in a Mouse Model of Down Syndrome
Authors: A. Salehi, M. Faizi, D. Colas, J. Valletta, J. Laguna, R. Takimoto-Kimura, A. Kleschevnikov, S. L. Wagner, P. Aisen, M. Shamloo, W. C. Mobley
Journal: Science Translational Medicine (2009)

Cognitive deficits in mice with a Down syndrome–like genetic defect can be reversed with precursors to the neurotransmitter norepinephrine.
Virus-replicating T cells in the immune response of mice. III. Role of vesicular stomatitis virus-replicating T cells in the antibody response.
Authors: N Minato, Y Katsura
Journal: The Journal of Experimental Medicine (1978)

The functional role of the T cell (Tv) which can replicate vesicular stomatitis virus (VSV) on activation by the antigen was investigated in antibody response in vitro. By the inoculation of VSV into the culture, marked augmentation of antibody response to sheep erythrocytes (SRBC) was observed in the culture of spleen cells taken more than 3 days after the immunization with SRBC, suggesting that the VSV-susceptible suppressor cells were included in these spleen cells and the activity was eliminated by the effect of VSV. Development of two distinct types of suppressor T cells was revealed in the spleen of mice after the priming with SRBC. First, nylon wool nonadherent (NAd) suppressor T cells found in the spleen cells taken 3 days after immunization, and second, nylon wool adherent (Ad) suppressor T cells found in the spleen cells taken approximately 1 wk after immunization. The activity of nylon Ad suppressor T cells was completely abolished by VSV-preinfection, whereas that of nylon NAd suppressor T cells was unaffected. It was also shown that the helper T-cell activity was not influenced by VSV-preinfection. These results provided direct evidence that nylon Ad suppressor T cell but not nylon NAd suppressor T cell nor helper T cell can actually replicate VSV after antigenic stimulation. Thus it was strongly suggested that Tv represents the nylon Ad suppressor T cells.
P23. Efficient ex vivo lysis of acute myeloid leukaemic (AML) cells mediated by triplebodies with dual-targeting capability in conjunction with natural killer cells as effectors
Authors: G Fey, TA Braciak, S Wildenhain, CC Roskopf, C Schiller, N Fenn, IA Schubert, U Jacob, KP Hopfner, FS Oduncu
Journal: Journal for ImmunoTherapy of Cancer (2014)

Meeting abstracts Current chemotherapy of acute myeloid leukaemia (AML) is limited by systemic toxicity. New agents are needed with increased selectivity for malignant cells and reduced toxicity. Triplebodies are a new class of antibody derivatives developed by our team, which consist of 3 antigen
Glycodelin: A Major Lipocalin Protein of the Reproductive Axis with Diverse Actions in Cell Recognition and Differentiation
Authors: Markku Seppälä, Robert N. Taylor, Hannu Koistinen, Riitta Koistinen, Edwin Milgrom
Journal: Endocrine Reviews (2002)

Glycodelin is a glycoprotein that belongs to the lipocalin superfamily. Depending on glycosylation, glycodelin appears in various isoforms. In the uterus, glycodelin-A is the major progesterone-regulated glycoprotein secreted into uterine luminal cavity by secretory/decidualized endometrial glands. The other tissues expressing glycodelin include fallopian tubes, ovary, breast, seminal vesicle, bone marrow, and eccrine glands. Glycodelin-A potently and dose-dependently inhibits human sperm-egg binding, whereas differently glycosylated glycodelin-S from seminal plasma has no such effect. Absence of contraceptive glycodelin-A in the uterus during periovulatory midcycle is consistent with an open "fertile window." Glycodelin induced by local or systemic administration of progestogens may potentially reduce the fertilizing capacity of sperm in any phase of the menstrual cycle. Glycodelin also has immunosuppressive activity. Its high concentration at the fetomaternal interface may contribute to protection of the embryonic semiallograft. Besides being an epithelial differentiation marker, glycodelin appears to play a role in glandular morphogenesis, as transfection of glycodelin cDNA into a glycodelin-negative breast cancer cells resulted in formation of gland-like structures, restricted proliferation, and induction of other epithelial markers. These various properties, as well as the chemistry, biology, and clinical aspects of glycodelin, continue to be areas of active investigation reviewed in this communication.
Interleukin-18 production and pulmonary function in COPD
Authors: H. Imaoka, T. Hoshino, S. Takei, T. Kinoshita, M. Okamoto, T. Kawayama, S. Kato, H. Iwasaki, K. Watanabe, H. Aizawa
Journal: European Respiratory Journal (2007)

Interleukin (IL)-18 production and pulmonary function were evaluated in patients with chronic obstructive pulmonary disease (COPD) in order to determine the role of IL-18 in COPD. Immunohistochemical techniques were used to examine IL-18 production in the lungs of patients with very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV, n = 16), smokers (n = 27) and nonsmokers (n = 23). Serum cytokine levels and pulmonary function were analysed in patients with GOLD stage I-IV COPD (n = 62), smokers (n = 34) and nonsmokers (n = 47). Persistent and severe small airway inflammation was observed in the lungs of ex-smokers with very severe COPD. IL-18 proteins were strongly expressed in alveolar macrophages, CD8+ T-cells, and both the bronchiolar and alveolar epithelia in the lungs of COPD patients. Serum levels of IL-18 in COPD patients and smokers were significantly higher than those in nonsmokers. Moreover, serum levels of IL-18 in patients with GOLD stage III and IV COPD were significantly higher than in smokers and nonsmokers. There was a significant negative correlation between serum IL-18 level and the predicted forced expiratory volume in one second in patients with COPD. In contrast, serum levels of IL-4, IL-13 and interferon-gamma were not significantly increased in any of the three groups. In conclusion, overproduction of interleukin-18 in the lungs may be involved in the pathogenesis of chronic obstructive pulmonary disease.
Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline Update
Authors: Ethan Basch, Ann Alexis Prestrud, Paul J. Hesketh, Mark G. Kris, Petra C. Feyer, Mark R. Somerfield, Maurice Chesney, Rebecca Anne Clark-Snow, Anne Marie Flaherty, Barbara Freundlich, Gary Morrow, Kamakshi V. Rao, Rowena N. Schwartz,, Gary H. Lyman
Journal: Journal of Clinical Oncology (2011)

To update the American Society of Clinical Oncology (ASCO) guideline for antiemetics in oncology.
Expression of transforming growth factor- (TGF ) and the TGF signalling molecule SMAD-2P in spontaneous and instability-induced osteoarthritis: role in cartilage degradation, chondrogenesis and osteophyte formation
Authors: E N Blaney Davidson, E L Vitters, P M van der Kraan, W B van den Berg
Journal: Annals of the Rheumatic Diseases (2006)

<b>Background:</b> The primary feature of osteoarthritis is cartilage loss. In addition, osteophytes can frequently be observed. Transforming growth factor-β (TGFβ) has been suggested to be associated with protection against cartilage damage and new cartilage formation as seen in osteophytes. <b>Objective:</b> To study TGFβ and TGFβ signalling in experimental osteoarthritis to gain insight into the role of TGFβ in cartilage degradation and osteophyte formation during osteoarthritis progression. <b>Methods:</b> Histological sections of murine knee joints were stained immunohistochemically for TGFβ3 and phosphorylated SMAD-2 (SMAD-2P). Expression patterns were studied in two murine osteoarthritis models, representing spontaneous (STR/ort model) and instability-associated osteoarthritis (collagenase-induced instability model). <b>Results:</b> TGFβ3 and SMAD-2P staining was increasingly reduced in cartilage during osteoarthritis progression in both models. Severely damaged cartilage was negative for TGFβ3. In contrast, bone morphogenetic protein-2 (BMP-2) expression was increased. In chondrocyte clusters, preceding osteophyte formation, TGFβ3 and SMAD-2P were strongly expressed. In early osteophytes, TGFβ3 was found in the outer fibrous layer, in the peripheral chondroblasts and in the core. Late osteophytes expressed TGFβ3 only in the fibrous layer. SMAD-2P was found throughout the osteophyte at all stages. In the late-stage osteophytes, BMP-2 was strongly expressed. <b>Conclusion:</b> Data show that lack of TGFβ3 is associated with cartilage damage, suggesting loss of the protective effect of TGFβ3 during osteoarthritis progression. Additionally, our results indicate that TGFβ3 is involved in early osteophyte development, whereas BMP might be involved in late osteophyte development.
Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a multicentre, randomized, observer-blind phase III study in comparison with a registered methyl-5-aminolaevulinate cream and placebo
Authors: T. Dirschka, P. Radny, R. Dominicus, H. Mensing, H. Brüning, L. Jenne, L. Karl, M. Sebastian, C. Oster-Schmidt, W. Klövekorn, U. Reinhold, M. Tanner, D. Gröne, M. Deichmann, M. Simon, F. Hübinger, G. Hofbauer, G. Krähn-Senftleben, F. Borrosch, K. Reich, C. Berking, P. Wolf, P. Lehmann, M. Moers-Carpi, H. Hönigsmann, K. Wernicke-Panten, C. Helwig, M. Foguet, B. Schmitz, H. Lübbert, R.-M. Szeimies
Journal: British Journal of Dermatology (2011)

Photodynamic therapy (PDT) with 5-aminolaevulinic acid (ALA) or its methylester [methyl-5-aminolaevulinate (MAL) or 5-amino-4-oxopentanoate] was recently ranked as first-line therapy for the treatment of actinic keratosis (AK) and is an accepted therapeutic option for the treatment of neoplastic skin diseases. BF-200 ALA (Biofrontera Bioscience GmbH, Leverkusen, Germany) is a gel formulation of ALA with nanoemulsion for the treatment of AK which overcomes previous problems of ALA instability and improves skin penetration.To evaluate the efficacy and safety of PDT of AKs with BF-200 ALA in comparison with a registered MAL cream and with placebo.The study was performed as a randomized, multicentre, observer-blind, placebo-controlled, interindividual trial with BF-200 ALA, a registered MAL cream and placebo in a ratio of 3:3:1. Six hundred patients, each with four to eight mild to moderate AK lesions on the face and/or the bald scalp, were enrolled in 26 study centres in Germany, Austria and Switzerland. Patients received one PDT. If residual lesions remained at 3months after treatment, PDT was repeated.PDT with BF-200 ALA was superior to placebo PDT with respect to patient complete clearance rate (78·2% vs. 17·1%; P<0·0001) and lesion complete clearance rate (90·4% vs. 37·1%) at 3months after the last PDT. Moreover, superiority was demonstrated over the MAL cream regarding the primary endpoint patient complete clearance (78·2% vs. 64·2%; P<0·05). Significant differences in the patient and lesion complete clearance rates and severity of treatment-related adverse events were observed for the narrow- and broad-spectrum light sources.BF-200 ALA is a very effective, well-tolerated new formulation for AK treatment with PDT and is superior to a registered MAL medication. Efficacies and adverse events vary greatly with the different light sources used.
Transposable Elements: Insertion Pattern and Impact on Gene Expression Evolution in Hominids
Authors: M. Warnefors, V. Pereira, A. Eyre-Walker
Journal: Molecular Biology and Evolution (2010)

Transposable elements (TEs) can affect the regulation of nearby genes through several mechanisms. Here, we examine to what extent recent TE insertions have contributed to the evolution of gene expression in hominids. We compare expression levels of human and chimpanzee orthologs and detect a weak increase in expression divergence (ED) for genes with species-specific TE insertions compared with unaffected genes. However, we show that genes with TE insertions predating the human–chimpanzee split also exhibit a similar increase in ED and therefore conclude that the increase is not due to the transcriptional influence of the TEs. These results are further confirmed by lineage-specific analysis of ED, using rhesus macaque as an outgroup: Human–chimpanzee ortholog pairs, where one ortholog has suffered TE insertion but not the other, do not show increased ED along the lineage where the insertion occurred, relative to the other lineage. We also show that genes with recent TE insertions tend to produce more alternative transcripts but find no evidence that the TEs themselves promote transcript diversity. Finally, we observe that TEs are enriched upstream relative to downstream of genes and show that this is due to insertional bias, rather than selection, because this bias is only observed in genes expressed in the germ line. This provides an alternative neutral explanation for the accumulation of TEs in upstream sequences.
Angina pectoris-like pain provoked by intravenous infusion of adenosine.
Authors: C Sylven
Journal: BMJ (1986)

<h3>BACKGROUND AND OBJECTIVES:</h3> Infratentorial superficial siderosis (iSS) is a rare but disabling neurological condition characterised by progressive hearing loss, balance and mobility problems. The functional decline in these neurological domains with iSS progression is likely to adversely impact health-related quality of life (HRQoL). We studied HRQoL of adults with iSS using two common generic HRQoL measures (Health Utilities Index Mark III (HUI3) and EuroQoL EQ5D (5 Level) to determine the most impacted domains and evaluate the association between HRQoL scores and disease duration. <h3>METHODS:</h3> This observational study was an anonymous online survey. Following institutional Research Ethics Committee approval, we contacted dedicated international organisations, charities and patient-groups identified through online searches, social media and collaborative networks, to distribute the study information and study link, inviting their members diagnosed with iSS to participate. Participation required access to a digital device connected to the internet, confirmation of eligibility (aged ≥18 years and previously diagnosed with iSS) and informed consent to participate in the survey, which included study-specific questions (demographics, iSS, hearing) and HRQoL questionnaires. Survey responses were captured by the Research Electronic Data Capture (REDCap) survey software and analysed using the SPSS statistical package. Linear regression analysis was performed to investigate the association between HRQoL scores and disease duration. <h3>RESULTS:</h3> Of fifty participants,60% were male; the median (interquartile range, IQR) age was 60 (15) years. The median (IQR) multi-attribute scores for HUI3 and EQ5D were 0.36 (0.53) and 0.64 (0.33), respectively. The most frequently affected domains (moderate or worse category) were hearing (64%), and pain (48%) for HUI3, and mobility (54%) and pain (50%) for EQ5D. There was a weak association between disease duration and multi-attribute scores for HUI3 (R=0.353; adjusted R<sup>2</sup>=0.096; b=-0.008; p=0.047) but not EQ5D. <h3>DISCUSSION:</h3> Our findings demonstrate low HRQoL scores which capture low functional status in several domains typically affected in iSS, suggesting that iSS has a major adverse impact on quality of life in multiple functional domains. Measures of HRQoL in iSS should be included in clinical and research settings, including treatment trials.