tbuckley/cabot-search huggingface dataset:
Developmental control of <i>CFTR</i>: from bioinformatics to novel therapeutic approaches
Authors: Catherine M. Greene, Dominik Hartl
Journal: European Respiratory Journal (2014)

Celebrating the 25th anniversary of identifying the genetic cause of cystic fibrosis (CF), tremendous progress has been made in the understanding and the treatment of this complex, but still fatal disease [1]. Despite advances, several key questions about the pathomechanisms of CF remain poorly understood. For instance, the precise genetic and epigenetic mechanisms that regulate expression and stability of the cystic fibrosis transmembrane conductance regulator ( CFTR ) gene remain incompletely defined. miRNA-binding blocker oligonucleotides offer an appealing option for developing tools to correct CFTR function <http://ow.ly/AjS8a>
Expression of CD163 prevents apoptosis through the production of granulocyte colony-stimulating factor in meningioma
Authors: H. Kanno, H. Nishihara, L. Wang, S. Yuzawa, H. Kobayashi, M. Tsuda, T. Kimura, M. Tanino, S. Terasaka, S. Tanaka
Journal: Neuro-Oncology (2013)

CD163 is a 130-kDa transmembrane protein expressed in human monocytes and macrophages, and the aberrant expression of CD163 in breast and colorectal cancer associated with patients' poor prognosis was reported. Here, we analyzed the expression of CD163 in meningioma, a common intracranial tumor, and its molecular mechanism in association with meningioma progression. First, we performed immunohistochemical analysis using 50 human meningioma specimens. Next, we established CD163-overexpressing human meningioma cell lines and investigated its roles in tumor progression in vitro and in vivo. Immunohistochemically, 26 of 50 human meningioma specimens (52.0%) were positive for CD163 in tumor cells, including benign grade I (48.5%) and grade II (71.4%) cases. Furthermore, CD163 expression was correlated with histological atypical parameters that directly predict the prognosis of meningioma. CD163-overexpressing meningioma cells showed significant suppression of apoptosis and accelerated tumor growth in nude mice. In addition, unexpected splenomegaly affiliated with the xenograft predicted tumor-derived granulocyte colony-stimulating factor (G-CSF) production, which was confirmed by reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assay. To our knowledge, this is the first report that demonstrates CD163 expression in meningioma not only by immunohistochemistry but also by reverse-transcription polymerase chain reaction, using primary culture cells, and provides the novel molecular function of CD163 to prevent apoptosis through the production of G-CSF in meningioma.
Standards of care for occupational asthma
Authors: D Fishwick, C M Barber, L M Bradshaw, J Harris-Roberts, M Francis, S Naylor, J Ayres, P S Burge, J M Corne, P Cullinan, T L Frank, D Hendrick, J Hoyle, M Jaakkola, A Newman-Taylor, P Nicholson, R Niven, A Pickering, R Rawbone, C Stenton, C J Warburton, A D Curran
Journal: Thorax (2007)

Occupational asthma remains a common disease in the UK with up to 3000 new cases diagnosed each year. The Health and Safety Executive (HSE) estimates the cost to our society to be over £1.1 billion for each 10-year period.1 In October 2001 the Health and Safety Commission agreed a package of measures aimed at reducing the incidence of asthma caused by exposure to substances in the workplace by 30% by 2010. Key to this aim are primary prevention by proper risk assessment and exposure control, together with secondary prevention to ensure reduction in the delay between the development of allergic symptoms at work (normally nasal or respiratory) and appropriate advice to the affected worker and workplace.

Conservative estimates suggest that one in 10 cases of adult onset asthma relate directly to sensitisation in the workplace,2 with a smaller subset of workers with acute irritant induced asthma. The latter—formerly termed reactive airway dysfunction syndrome (RADS)—relates to asthma caused by exposure to high levels of airborne irritants.

The prognosis of individuals with occupational asthma is better if they are removed from exposure quickly, particularly within a year of first symptoms.3–5 However, removing individuals often leads to unemployment. If the diagnosis of occupational asthma is incorrect, advising individuals whose asthma is not caused by work to be removed from exposure may have unnecessary financial and social consequences.

The intent of this article is not to document the entire current evidence base related to occupational asthma, as the British Occupational Health Research Foundation (BOHRF) recently completed such an evidence review.7 The key points of this article are summarised in box …
Long-Term Persistence of a Polyclonal T Cell Repertoire After Gene Therapy for X-Linked Severe Combined Immunodeficiency
Authors: H. Bobby Gaspar, Samantha Cooray, Kimberly C. Gilmour, Kathryn L. Parsley, Stuart Adams, Steven J. Howe, Abdulaziz Al Ghonaium, Jinhua Bayford, Lucinda Brown, E. Graham Davies, Christine Kinnon, Adrian J. Thrasher
Journal: Science Translational Medicine (2011)

X-linked severe combined immunodeficiency (SCID-X1) is caused by mutations in the common cytokine receptor γ chain. These mutations classically lead to complete absence of functional T and natural killer cell lineages as well as to intrinsically compromised B cell function. Although human leukocyte antigen (HLA)-matched hematopoietic stem cell transplantation (HSCT) is highly successful in SCID-X1 patients, HLA-mismatched procedures can be associated with prolonged immunodeficiency, graft-versus-host disease, and increased overall mortality. Here, 10 children were treated with autologous CD34(+) hematopoietic stem and progenitor cells transduced with a conventional gammaretroviral vector. The patients did not receive myelosuppressive conditioning and were monitored for immunological recovery after cell infusion. All patients were alive after a median follow-up of 80 months (range, 54 to 107 months), and a functional polyclonal T cell repertoire was restored in all patients. Humoral immunity only partially recovered but was sufficient in some patients to allow for withdrawal of immunoglobulin replacement; however, three patients developed antibiotic-responsive acute pulmonary infection after discontinuation of antibiotic prophylaxis and/or immunoglobulin replacement. One patient developed acute T cell acute lymphoblastic leukemia because of up-regulated expression of the proto-oncogene LMO-2 from insertional mutagenesis, but maintained a polyclonal T cell repertoire through chemotherapy and entered remission. Therefore, gene therapy for SCID-X1 without myelosuppressive conditioning effectively restored T cell immunity and was associated with high survival rates for up to 9 years. Further studies using vectors designed to limit mutagenesis and strategies to enhance B cell reconstitution are warranted to define the role of this treatment modality alongside conventional HSCT for SCID-X1.
Impaired Myocardial Perfusion Is a Major Explanation of the Poor Outcome Observed in Patients Undergoing Primary Angioplasty for ST-Segment–Elevation Myocardial Infarction and Signs of Heart Failure
Authors: Giuseppe De Luca, Arnoud W.J. van’t Hof, Menko-Jan de Boer, Jan C.A. Hoorntje, A.T. Marcel Gosselink, Jan-Henk E. Dambrink, Jan Paul Ottervanger, Felix Zijlstra, Harry Suryapranata
Journal: Circulation (2004)

The aim of the present study was to investigate the prognostic implication of myocardial perfusion in patients with ST-segment-elevation myocardial infarction (STEMI) and signs of heart failure, treated with primary angioplasty.Our population is represented by 1548 consecutive patients undergoing primary angioplasty for STEMI. Congestive heart failure was defined as Killip class >1 at admission. Killip class was linearly associated with myocardial perfusion, enzymatic infarct size, predischarge ejection fraction, and 1-year mortality rate. Myocardial blush was an independent predictor of 1-year mortality (RR [95% CI]=2.92 [1.37 to 6.23], P=0.005) in patients with advanced Killip class at presentation.Our study shows that patients with heart failure complicating STEMI have impaired myocardial perfusion, which accounts for the poor outcome observed in these patients. Further efforts should be aimed at improving myocardial perfusion, beyond epicardial recanalization, to further improve the outcome of these high-risk patients.
Hemoglobin synthesis in β-thalassemia: the properties of the free α-chains
Authors: Arthur Bank
Journal: Journal of Clinical Investigation (1968)

The decrease in hemoglobin A (HbA, alpha(2)beta(2)) synthesis in the erythroid cells of patients with beta-thalassemia is due to a selective defect in beta-chain synthesis. Since alpha-chains continue to be formed at a normal rate in these cells, this results in a marked relative excess of alpha-chain synthesis over beta- and gamma-chain synthesis. The alpha-chains uncombined with beta- or beta-like-chains (delta, gamma) will be referred to as free alpha-chains. The experiments presented in this paper show that these free alpha-chains are capable of combining with beta-chains to form HbA and are, therefore, structurally normal. Alternatively, in the absence of added beta-chains, alpha-chains aggregates of various sizes are formed. Peripheral blood from patients with beta-thalassemia was incubated with radioactive amino acids and hemolysates were prepared. Column chromatography demonstrates that a majority of the free alpha-chains are not present in HbA. They are strongly bound to carboxymethylcellulose resin at pHs from 7.0 to 10.0, and do not elute with HbA. However, when chemically prepared hemoglobin H (Hbbeta(4)) is added to the fresh hemolysates, the free alpha-chains are readily recovered in the HbA peak. This indicates that the free alpha-chains are able to combine normally with beta-chains to form HbA. Freshly labeled hemolysates were also subjected to Sephadex G-100 chromatography. The free alpha-chains eluted as a broad peak migrating between myoglobin and hemoglobin, consistent with their forming alpha-chain aggregates of various mol wt between 16,000 and 64,000. It is suggested that the chromatographic behavior of the free alpha-chains reported herein simply reflects the chemical properties of normal alpha-chains in the absence of adequate numbers of beta- or gamma-chains. The tendency of these free alpha-chains to aggregate may lead to their intracellular precipitation and the subsequent destruction of the cells containing them.
Three distinct mechanisms predominate in non-contact anterior cruciate ligament injuries in male professional football players: a systematic video analysis of 39 cases
Authors: Markus Waldén, Tron Krosshaug, John Bjørneboe, Thor Einar Andersen, Oliver Faul, Martin Hägglund
Journal: British Journal of Sports Medicine (2015)

Background Current knowledge on anterior cruciate ligament (ACL) injury mechanisms in male football players is limited. Aim To describe ACL injury mechanisms in male professional football players using systematic video analysis. Methods We assessed videos from 39 complete ACL tears recorded via prospective professional football injury surveillance between 2001 and 2011. Five analysts independently reviewed all videos to estimate the time of initial foot contact with the ground and the time of ACL tear. We then analysed all videos according to a structured format describing the injury circumstances and lower limb joint biomechanics. Results Twenty-five injuries were non-contact, eight indirect contact and six direct contact injuries. We identified three main categories of non-contact and indirect contact injury situations: (1) pressing (n=11), (2) re-gaining balance after kicking (n=5) and (3) landing after heading (n=5). The fourth main injury situation was direct contact with the injured leg or knee (n=6). Knee valgus was frequently seen in the main categories of non-contact and indirect contact playing situations (n=11), but a dynamic valgus collapse was infrequent (n=3). This was in contrast to the tackling-induced direct contact situations where a knee valgus collapse occurred in all cases (n=3). Conclusions Eighty-five per cent of the ACL injuries in male professional football players resulted from non-contact or indirect contact mechanisms. The most common playing situation leading to injury was pressing followed by kicking and heading. Knee valgus was frequently seen regardless of the playing situation, but a dynamic valgus collapse was rare.
Airway response to methacholine during exercise induced refractoriness in asthma.
Authors: H Magnussen, G Reuss, R Jorres
Journal: Thorax (1986)

To investigate the mechanisms contributing to refractoriness in exercise induced asthma a methacholine challenge test was performed 30 minutes before and 30 minutes after two exercise tests 45 minutes apart. Exercise was performed by 12 asthmatic patients while they were breathing cold air. There was a smaller airway response to the second exercise test than to the first, though there was wide variation between subjects. The response to the second methacholine challenge was reduced in some patients but showed no significant change overall. Refractoriness to exercise induced asthma positively correlated with a reduced response to methacholine. These data suggest that mediator depletion does not fully explain refractoriness.
OC-080 Reduced circulating FGF19 levels are associated with symptoms of diarrhoea in crohn's disease
Authors: J D Nolan, I Johnston, T Dew, S Pattni, T Orchard, J R Walters
Journal: Gut (2012)

<h3>Introduction</h3> FGF19 is a polypeptide hormone produced in the ileum which inhibits hepatic synthesis of bile acid and is thought to have roles in regulation of bile acid pool size and in clinical conditions of diarrhoea. Fasting serum levels of FGF19 are reduced in patients with Crohn9s disease (CD) involving the ileum and also in patients with CD and ileal resections (IR). Aims: To investigate the relationship between serum FGF19 and disease activity in CD and length of ileal resection. <h3>Methods</h3> Blood samples were taken prospectively from patients after an overnight fast in 40 patients with Crohn9s disease (24 non resected and 16 with previous IR), 19 healthy controls and 75 disease controls with SeHCAT negative chronic idiopathic diarrhoea. In 9 IR patients clinical records were available to establish the precise length of ileum resected. Disease activity was assessed by Harvey-Bradshaw Index (HBI). Diarrhoea was defined as stool frequency ≥3, Bristol stool chart ≥6. Serum FGF19 was measured by ELISA and data are expressed as medians and ranges. Nonparametric statistical tests (Mann–Whitney and Spearman rank correlations) were used. <h3>Results</h3> Median levels of FGF19 were significantly lower in patients with non-resected CD (114 pg/ml, 3–339) compared to healthy controls (231 pg/ml, 74–655, p=0.002 and 0.005 respectively). Patients with previous IR (71 pg/ml, 17–152) had significantly lower levels than non-resected CD (p<i>=</i>0.02). Out of 15 patients with non resected CD with ileal or ileo-colonic disease, eight had active disease (HBI&gt;4) and had further radiological or endoscopic assessment of the ileum: four with symptomatic strictures had significantly higher FGF19 levels (328 pg/ml, 178–339) compared to the inactive patients (118 pg/ml, 46–256, p=0.04). Conversely, four with non-obstructive ileal inflammation had significantly lower FGF19 levels (33 pg/ml, 3–59) than inactive patients (p<i>=</i>0.01) and this group had the lowest observed levels of FGF19. Six non resected CD with diarrhoea had significantly lower levels of FGF19 (86 pg/ml, 30–169) compared to the diarrhoea controls (246 pg/ml, 72–1000, p=&lt;0.0001). In nine IR patients an inverse correlation between FGF19 levels and resection length was observed (<i>r=</i>−0.81, p 0.01). <h3>Conclusion</h3> Fasting serum levels of FGF19 are significantly reduced by IR or non obstructive ileal inflammation. Symptoms of diarrhoea in CD are associated with low levels of FGF19 and an inverse correlation is found between FGF19 and the length of previous ileal resections. <h3>Competing interests</h3> None declared.
CD39/CD73/A2AR pathway may involve in the occurrence allergic asthma
Authors: Linlin Wang, Guochao Shi, Huanying Wan
Journal: European Respiratory Journal (2013)

Objective  The ecto-enzyme CD39 and CD73 can successively hydrolyze extracellular ATP which has pro-inflammatory effects into AMP and adenosine. Accordingly, CD39 exerts its anti-inflammatory effects by removal extracellular ATP. Moreover, the produced adenosine can inhibit the activation and functions of effector T cells by combining to adenosine receptor A2A (A2AR). But CD39, CD73 and A2AR expression in patients with allergic asthma remains unknown.  Methods  Eighteen patients with persistent asthma allergic to house dust mites and nineteen healthy volunteers were enrolled.The expression of CD39, CD73, A2AR mRNA in PBMC were determined by SYRB Green I Real-time PCR. DP.sIgE(Dermatophagoides pteronyssinus specific immunoglobulin E) was detected by ELISA.  Results  Our data showed that the expression of CD39 mRNA in patients with asthma was significantly lower than that in normal controls (1.49±0.59×10 -3  vs 2.17±0.77×10 -3 ,  P  -3  vs 1.03±0.39×10 -3 ,  P >0.05). The expression of A2AR mRNA in patients with asthma was significantly higher than that in normal controls (0.45±0.29×10 -3  vs 0.21±0.06×10 -3 ,  P  Conclusions  The signal pathway of CD39/CD73/A2AR may participate in the occurrence of allergic asthma.
Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta2 adrenoceptors in the sinoatrial node
Authors: D. B FRIEDMAN, T. I MUSCH, R S. WILLIAMS, G. A ORDWAY
Journal: Cardiovascular Research (1987)

Journal Article Beta adrenergic blockade with propranolol and atenolol in the exercising dog: evidence for beta2 adrenoceptors in the sinoatrial node Get access DANIEL B FRIEDMAN, DANIEL B FRIEDMAN From the Departments of Internal Medicine and Physiology, University Texas Health Science Center, Dallas; Southwestern Medical School, Dallas, Texas; and Duke University Medical Center, Durham, North Carolina, USA Address for correspondence and reprints: Dr Daniel B Friedman, c/o Dr R S Williams, Box 3945, Duke University Medical Center, Durham, North Carolina 27710, USA. Search for other works by this author on: Oxford Academic PubMed Google Scholar TIMOTHY I MUSCH, TIMOTHY I MUSCH From the Departments of Internal Medicine and Physiology, University Texas Health Science Center, Dallas; Southwestern Medical School, Dallas, Texas; and Duke University Medical Center, Durham, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar R SANDERS WILLIAMS, R SANDERS WILLIAMS From the Departments of Internal Medicine and Physiology, University Texas Health Science Center, Dallas; Southwestern Medical School, Dallas, Texas; and Duke University Medical Center, Durham, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar GEORGE A ORDWAY GEORGE A ORDWAY From the Departments of Internal Medicine and Physiology, University Texas Health Science Center, Dallas; Southwestern Medical School, Dallas, Texas; and Duke University Medical Center, Durham, North Carolina, USA Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 21, Issue 2, February 1987, Pages 124–129, https://doi.org/10.1093/cvr/21.2.124 Published: 01 February 1987 Article history Received: 29 January 1986 Accepted: 08 July 1986 Published: 01 February 1987
Linkage‐disequilibrium of the senegal haplotype with the β<sup>s</sup> gene in the republic of guinea
Authors: Alhassane Sow, Eleanor Peterson, Olgiça Josifovska, Mary E. Fabry, Rajagopal Krishnamoorthy, Ronald L. Nagel
Journal: American Journal of Hematology (1995)

Abstract We have determined the β gene cluster haplotype in 40 chromosomes carrying the β s mutation from individuals of the major ethnic groups living in the Republic of Guinea. Thirty‐one of these were either the typical (n = 29) or the atypical (n = 2) Senegal haplotype demonstrating that in this region of Atlantic West Africa, the sickle mutation is in linkage disequilibrium with this particular β‐gene cluster haplotype. Two individuals carrying one chromosome bearing the Benin haplotype were of Malinke ethnic origin. This is in keeping with the hypothesis that the Senegal β‐gene cluster haplotype is linked to the β s gene in Atlantic West Africa.
Intraperitoneal Cisplatin and Paclitaxel in Ovarian Cancer
Authors: Deborah K. Armstrong, Brian Bundy, Lari Wenzel, Helen Q. Huang, Rebecca Baergen, Shashikant Lele, Larry J. Copeland, Joan L. Walker, Robert A. Burger
Journal: New England Journal of Medicine (2006)

Standard chemotherapy for newly diagnosed ovarian cancer is a platinum-taxane combination. The Gynecologic Oncology Group conducted a randomized, phase 3 trial that compared intravenous paclitaxel plus cisplatin with intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel in patients with stage III ovarian cancer.We randomly assigned patients with stage III ovarian carcinoma or primary peritoneal carcinoma with no residual mass greater than 1.0 cm to receive 135 mg of intravenous paclitaxel per square meter of body-surface area over a 24-hour period followed by either 75 mg of intravenous cisplatin per square meter on day 2 (intravenous-therapy group) or 100 mg of intraperitoneal cisplatin per square meter on day 2 and 60 mg of intraperitoneal paclitaxel per square meter on day 8 (intraperitoneal-therapy group). Treatment was given every three weeks for six cycles. Quality of life was assessed.Of 429 patients who underwent randomization, 415 were eligible. Grade 3 and 4 pain, fatigue, and hematologic, gastrointestinal, metabolic, and neurologic toxic effects were more common in the intraperitoneal-therapy group than in the intravenous-therapy group (P< or =0.001). Only 42 percent of the patients in the intraperitoneal-therapy group completed six cycles of the assigned therapy, but the median duration of progression-free survival in the intravenous-therapy and intraperitoneal-therapy groups was 18.3 and 23.8 months, respectively (P=0.05 by the log-rank test). The median duration of overall survival in the intravenous-therapy and intraperitoneal-therapy groups was 49.7 and 65.6 months, respectively (P=0.03 by the log-rank test). Quality of life was significantly worse in the intraperitoneal-therapy group before cycle 4 and three to six weeks after treatment but not one year after treatment.As compared with intravenous paclitaxel plus cisplatin, intravenous paclitaxel plus intraperitoneal cisplatin and paclitaxel improves survival in patients with optimally debulked stage III ovarian cancer.
The clinical and metabolic significance of jejunal diverticula
Authors: W. T. Cooke, E. V. Cox, D. J. Fone, M. J. Meynell, R. Gaddie
Journal: Gut (1963)

A study of 33 patients with jejunal diverticula showed that all except four had symptoms or metabolic upsets attributable to the presence of the diverticula. A disturbance of vitamin B12 metabolism or absorption was found in 16 patients and neuropathy was found in 12 patients. It is considered that abnormal bacterial activity in the small intestine is an important factor in these patients.