tbuckley/cabot-search huggingface dataset:
P2-01-19: Expression of Receptor Like Protein Tyrosine Phosphatases mu (PTPRM) in Breast Cancer and the Biological Effects of PTPRM on Breast Cancer Cells.
Authors: P-H Sun, L Ye, RE Mansel, WG Jiang
Journal: Cancer Research (2011)

Abstract Introduction: Protein tyrosine phosphatases (PTPs) play a major role in many cellular functions including cell survival, proliferation, differentiation and motility. The receptor-like protein tyrosine phosphatase mu (PTPRM) has a similar structure to cell-cell adhesion molecules and has been shown to exhibit homophilic binding and confer cell-cell adhesion in cells including epithelial and cancer cells. However, the role played by PTPRM in breast cancer remains unclear. The present study investigated the expression of PTPRM in breast cancer and the biological impact of PTPRM on breast cancer cells. Methods: Expression of PTPRM protein and gene transcript was examined in a cohort of primary breast cancer tumours. The association of PTPRM transcripts level and pathological and clinical aspects was then analysed. Expression of PTPRM transcript in breast cancer cells were knocked down using a specific anti-PTPRM transgene. The impact of PTPRM knockdown on breast cancer was evaluated using a series of in vitro cell models and in vivo tumour model. Result: PTPRM protein was seen generally distributed in the breast tissues, including tumours and normal background tissues. A stronger staining was revealed in cytoplasm of both mammary epithelia and cancer cells in comparison with the surrounding stromal cells. A significantly decrease was seen in poorly differentiated tumours (92.5±279), and moderately differentiated tumours (288±110), compared with that of well differentiated (472±114), p=0.011 and p=0.031 respectively. PTPRM transcript levels were decreased in patients died from breast cancer. The expression of PTPRM transcripts was significantly associated with disease free survival. Patients with lower expression of PTPRM had shorter survival compared with those with high level of PTPRM expression (p=0.029). Knocking down PTPRM from breast cancer cells significantly increased cell adhesion compared with control cells (p&amp;lt;0.001). Likewise, the knockdown also marked increase the rate of cell migration (102.9±11.3μm for control vs 115.3±10.5μm for PTPRM knockdown, p&amp;lt;0.05). Conclusion: The expression of PTPRM transcripts is decreased in poorly differentiated breast tumours and is correlated with poorer long term survival. This is likely to be contributed to by the biological impact of PTPRM on the aggressiveness of breast cancer cells. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-01-19.
The physiological basis of pulmonary gas exchange: implications for clinical interpretation of arterial blood gases
Authors: Peter D. Wagner
Journal: European Respiratory Journal (2014)

The field of pulmonary gas exchange is mature, with the basic principles developed more than 60 years ago. Arterial blood gas measurements (tensions and concentrations of O₂ and CO₂) constitute a mainstay of clinical care to assess the degree of pulmonary gas exchange abnormality. However, the factors that dictate arterial blood gas values are often multifactorial and complex, with six different causes of hypoxaemia (inspiratory hypoxia, hypoventilation, ventilation/perfusion inequality, diffusion limitation, shunting and reduced mixed venous oxygenation) contributing variably to the arterial O₂ and CO₂ tension in any given patient. Blood gas values are then usually further affected by the body's abilities to compensate for gas exchange disturbances by three tactics (greater O₂ extraction, increasing ventilation and increasing cardiac output). This article explains the basic principles of gas exchange in health, mechanisms of altered gas exchange in disease, how the body compensates for abnormal gas exchange, and based on these principles, the tools available to interpret blood gas data and, quantitatively, to best understand the physiological state of each patient. This understanding is important because therapeutic intervention to improve abnormal gas exchange in any given patient needs to be based on the particular physiological mechanisms affecting gas exchange in that patient.
Evaluating the health effects of social interventions
Authors: H. Thomson
Journal: BMJ (2004)

Is no evidence better than any evidence when controlled studies are unethical? 

Rigorous evidence on the health effects of social interventions is scarce1 2 despite calls for more evidence from randomised studies.3 One reason for the lack of such experimental research on social interventions may be the perception among researchers, policymakers, and others that randomised designs belong to the biomedical world and that their application to social interventions is both unethical and simplistic.4 Applying experimental designs to social interventions may be problematic but is not always impossible and is a desirable alternative to uncontrolled experimentation.3 However, even when randomised designs have been used to evaluate social interventions, opportunities to incorporate health measures have often been missed.5 For example, income supplementation is thought to be a key part of reducing health inequalities,6 but rigorous evidence to support this is lacking because most randomised controlled trials of income supplementation have not included health measures.5 Current moves to increase uptake of benefits offer new opportunities to establish the effects of income supplements on health. In attempting to design such a study, however, we found that randomised or other controlled trials were difficult to justify ethically, and our eventual design was rejected by funders.

#### Box 1 Attendance allowance

A pilot study carried out by one of us (RH) showed substantial health gains among elderly people after receipt of attendance allowance. We therefore decided to pursue a full scale study of the health effects of income supplementation. …
Premature Closure of the Mitral and Tricuspid Valves
Authors: DONALD A. SPRING, JOHN D. FOLTS, WILLIAM P. YOUNG, GEORGE G. ROWE
Journal: Circulation (1972)

Premature closure of an atrioventricular valve was observed in 80 of a group of 519 subjects catheterized for aortic insufficiency (AI) or mitral insufficiency (MI), or both. Sole premature mitral closure (PMC) was present in nine subjects, sole premature tricuspid closure (PTC) in 40, and combined PMC and PTC in 31. Clinically PMC was associated with a first sound that was soft or absent in 75% and an atrial contraction sound in 50% of the subjects with dominant aortic insufficiency. PMC or PTC, or both, were verified at surgery in three subjects and were produced experimentally in intact dogs by acute AI. The presence of PMC and PTC appears related to the severity and chronicity of valvular disease.
136. Recombinant Adeno-Associated Virus 2-Mediated Ectopic Expression of α4β1 Integrin in Mouse Mesenchymal Stem Cells Enhances Repopulation to Bone upon Syngeneic Transplantation in an Immunocompetent Mouse Model
Authors: Sanjay Kumar, Selvarangan Ponnazhagan
Journal: Molecular Therapy (2005)

Ex-vivo therapy with mesenchymal stem cells (MSC) is a novel approach for the treatment of genetic, age-related or segmental defects to increase bone mass. Recent identification that MSC differentiate into lineages that form bone, cartilage, adipose tissue, fibroblasts, neurons and cardiac tissues under controlled conditions offers unique advantage for potentially utilizing them in cell therapy or gene therapy. The pluripotent property of MSC necessitates selection of lineage-specific cells or restricted expression of therapeutic genes into committed progenitors with specific phenotypes for regulated gene therapy. Despite the potential of MSC to differentiate into desired lineages under controlled culture conditions, major limitation in the utilization of the culture-expanded MSC remains in the inability to restrict homing to bone upon autologous transfer. More recently, it is becoming increasingly evident that homing of hematopoietic stem cells to bone is critically dependent on the expression of matrix associated proteins, which interact with receptors on cells in the bone marrow. One of the matrix proteins that has been shown to effect significant influence on homing of not only hematopoietic stem cells but also of metastatic tumor cells to bone is the |[alpha]|4|[beta]|1integrin. |[alpha]|4|[beta]|1 integrin is a cell surface heterodimer, which mediates cell-cell and cell-extracellular matrix interactions. Towards developing conditions that will promote homing of the ex vivo modified MSC to bone and to test the hypothesis that enrichment of progenitor phenotype and homing signal on ex vivo cultured MSC, will enhance homing to bone upon systemic transplantation, bone marrow stromal cells from male C57BL/6 mouse were transduced with a recombinant AAV2 encoding mouse |[alpha]|4|[beta]|1 integrin. The cells were cultured for 10 days in the presence of 10-9 M FGF2 to avoid differentiation. Approximately 107 cells were transplanted into female recipients by tail vein injection. Cohorts of mice also received untransduced or rAAV2-GFP transduced MSC. Animals were sacrificed 15days post transplantation and tissues including lung, liver, adipose tissues, spleen, kidney, muscle, lymph node and bone marrow were harvested. FACS analysis of cultured bone marrow stromal cells from control and experimental mice, in situ hybridization of tissue with Y-chromosome specific probe, real-time PCR and southern blot analyses established significantly higher percentage of bone homing of culture-expanded MSC, transduced with rAAV expressing |[alpha]|4|[beta]|1 integrin. These studies indicate that rAAV encoding a4b1integrin can be effectively used to transduce MSC ex vivo to achieve enhanced repopulation of gene-modified MSC to bone, and can be combined with other cell/gene therapy applications for targeted delivery of therapeutic proteins.
Diffuse Gastric Antral Vascular Ectasia: Cause of Chronic Gastrointestinal Blood Loss
Authors: T. Arendt, M. Barten, V. Lakner, R. Arendt
Journal: Endoscopy (1987)

See also: Gastric Antral Vascular Ectasia and Primary Biliary CirrhosisEndoscopy 1988; 20(06): 334-334DOI: 10.1055/s-2007-1018210
Reactivity of autoantibodies of autoimmune hemolytic anemia with recombinant rhesus blood group antigens or anion transporter band3
Authors: Sadahiko Iwamoto, Toyomi Kamesaki, Takasi Oyamada, Hiroshi Okuda, Maki Kumada, Toshinori Omi, Junko Takahashi, Yoshihiko Tani, Mitsuhiro Omine, Eiji Kajii
Journal: American Journal of Hematology (2001)

Abstract The specificity of autoantibodies in autoimmune hemolytic anemia (AIHA) has been studied using the serological procedure and immunoprecipitation technique with rare phenotype red cells. We attempted to analyze specificity using recombinant rhesus (Rh) blood group and band3 antigens expressed on erythroleukemic cell lines, KU812E. The autoantibody eluates were isolated by the acid elution procedure from the red cells of 20 AIHA patients. The recombinant Rh antigens, RhD, cE, ce, CE, and chimera antigens CE‐D and D‐CE, were obtained by retroviral cDNA transduction into KU812E cells, and the cell line expressing the antigens was cloned. Band3 cDNA was also obtained and introduced into KU812E and cloned KU812 expressing RhcE. The reactivities of AIHA eluates with recombinant Rh and band3 antigens were studied by flow cytometry. Fifteen eluates reacted with at least one of the RhcE, ce, or CE antigens, and four eluates reacted with RhD. Seven eluates with strong Rh specificity were studied further using chimera antigen. Five eluates showed reduced or lost reactivity, although two eluates reacted identically with the chimera antigens as wild type. These results indicated that conformational epitopes constituted by RhD or CE specific exofacial peptide loops are important for autoantibodies in most cases. Seven eluates reacted with band3, five exclusively. The coexpression study of RhcE and band3 did not enhance the expression of either antigen nor the reactivity with patient eluates, indicating that association of Rh and band3 was not involved in the appearance of autoantigen. Am. J. Hematol. 68:106–114, 2001. © 2001 Wiley‐Liss, Inc.
Light activates the adrenal gland: Timing of gene expression and glucocorticoid release
Authors: Atsushi Ishida, Tatsushi Mutoh, Tomoko Ueyama, Hideki Bando, Satoru Masubuchi, Daiichiro Nakahara, Gozoh Tsujimoto, Hitoshi Okamura
Journal: Cell Metabolism (2005)
Glucagon for Propranolol Overdose-Reply
Authors: Richard C. Smith
Journal: JAMA (1986)

<h3>In Reply.—</h3> The authors infer that 50 mg of phenol will cause toxic manifestations, when in fact, this amount has rarely if ever caused side effects when glucagon has been used as an antidote for β-blocker overdose.<sup>1</sup>Acute oral injestions of 1 to 2 g or more of phenol usually result in the aforementioned toxic side effects.<sup>2-4</sup>Since the majority of patients with propranolol overdose have required fewer than 24 hours of glucagon infusion (5 mg/hr or less),<sup>1</sup>the recommended use of dextrose or saline as a diluent (shelf life cannot be guaranteed by the manufacturer) may not be appropriate. Overdose with β-blockers with a longer half-life or with sustainedrelease preparations may require longer glucagon infusions. In this setting, the use of a nonphenolcontaining diluent may be indicated.
Randomized, Double-Blind, Placebo-controlled Study of Brodalumab, a Human Anti–IL-17 Receptor Monoclonal Antibody, in Moderate to Severe Asthma
Authors: William W. Busse, Stephen Holgate, Edward Kerwin, Yun Chon, JingYuan Feng, Joseph Lin, Shao-Lee Lin
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

IL-17 signaling has been implicated in development and persistence of asthma. Cytokine-targeted strategies blocking IL-17 receptor signaling may be beneficial in asthma treatment.To determine efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody, in subjects with inadequately controlled moderate to severe asthma taking regular inhaled corticosteroids.Three hundred two subjects were randomized to brodalumab (140, 210, or 280 mg) or placebo. Primary endpoint was change in Asthma Control Questionnaire (ACQ) score from baseline to Week 12. Secondary endpoints included FEV1, symptom scores, and symptom-free days. Prespecified subgroup analyses were conducted to identify potential responsive subpopulations. Analyses included randomized subjects receiving one or more doses of investigational product using last-observation-carried-forward imputation.Demographics and baseline characteristics were generally balanced among groups (n = 302; n = 226 brodalumab). For the overall study population, no treatment differences were observed. Nine prespecified subgroups were examined without corrections for multiple testing. In only the high-reversibility subgroup (post-bronchodilator FEV1 improvement ≥ 20%; n = 112) was an ACQ change with nominal significance noted; ACQ responses were nominally significant in the 210-mg group (estimated treatment difference, 0.53) but not significant in the higher 280-mg group (estimated treatment difference, 0.38). Adverse events, generally balanced among groups, were most commonly asthma, upper respiratory tract infection, and injection site reaction.Inhibition of IL-17 receptor A did not produce a treatment effect in subjects with asthma. The results of the high-reversibility subgroup analysis are of uncertain significance, requiring further study of brodalumab in this asthma subpopulation. Clinical trial registered with www.clinicaltrials.gov (NCT01199289).
Audit finds 24 000 excess deaths among people with diabetes in England and Wales
Authors: Z. Kmietowicz
Journal: BMJ (2012)

An audit of nearly two million people with diabetes in England and Wales has found that in 2010-11 about 45 000 of them had heart failure, 17 700 (65%) more than the number that would be expected in the general population (27 300).1

However, the risk of heart failure varied widely across England and Wales. After standardisation to minimise differences in local populations, such as age and sex, the risk of heart failure in patients with diabetes in Havering was 27% more than the general population, while in Kensington and Chelsea it was 164% higher.

The national diabetes audit of diabetes related complications and mortality has quantified the risks of cardiovascular complications among people with diabetes for the first time. It included 85% of people with diabetes …
A new enrichment model for high sensitivity detection and downstream analyses of circulating tumor cells in breast cancer patients.
Authors: G Deng, M Mishaeli, M Miller, AA Zayed, D Huntsman, K Gelmon, R Yerushalmi, E Manna, D Krag, I Habib, J Williamson, J Burke
Journal: Cancer Research (2009)

Abstract Abstract #4162 The detection of circulating tumor cells (CTCs) in breast cancer patients have the potential to improve prognostication and the monitoring of response to treatment. Most CTC enrichment technologies are based on binding to anti-EpCAM antibodies. The sensitivity of such assays is limited by tumors that express no or undetectable levels of EpCAM. Improvements in CTC detection coupled with the development of systems to interrogate CTCs for therapeutic target expression could lead to novel applications for patient monitoring, clinical diagnosis and treatment. In this study, we describe a sensitive and reproducible enrichment method for CTCs. We defined cells as circulating tumor cells with three criteria: Positive for cytokeratin (CK+) and DAPI (nuclear) (DAPI+) and negative staining for CD45 (CD45-). We have previously reported that this system has a higher sensitivity for circulating tumor cell detection and provides a better platform for CTC downstream analyses compare to the methods currently available in the market. Herein, we describe the use of this platform for the evaluation of breast cancer biomarkers in CTCs. Blood samples from patients with metastatic breast cancer were used for CellSearch™ assay (Veridex , LLC ) and our CTC assay (A1000 CTC enrichment and detection kit, Genetix). We performed the CTC enrichment assay using the combination of anti-CK and anti-EpCAM antibodies. CTCs were identified with brightfield and fluorescence labeled anti-CK, anti-CD45 and DAPI (nuclear stain) images. The Ariol® system (Applied Imaging Corporation) was employed for automated cell image capture and analysis of CTCs on glass slides. CTCs enriched on the glass slides were used for CTC downstream analysis. Our CTC enrichment model is designed to have the capability to enrich all the three types of CTCs including CK+ &amp; EpCAM+, CK+ &amp; EpCAM-/low and CK-/low &amp; EpCAM+ cells. Compared to the enrichment methods using anti-EpCAM or anti-cytokeratin antibody alone, a higher CTC detection rate and a larger dynamic CTC detected range were obtained with our new enrichment model. Interestingly there were clear CTC number differences with enrichment methods in the higher CTC count patient samples which indicate that the different enrichment methods may enrich different types of CTCs from patient blood samples.&amp;#x2028; Results of DNA and RNA FISH analyses on enriched CTCs indicate that the CTCs on glass slides can be used for its downstream analyses directly or indirectly. Our method may have better performance on enrichment of heterogeneous CTCs and provide a better platform for CTCs profiling for biomarker evaluations and CTC downstream analyses. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4162.
On Management of Neonatal Asphyxia
Authors: Albert D. Warshauer
Journal: JAMA (1979)

ABSTRACT To the Editor.— Drs Peterson and Gregory (241:1835, 1979) have asked and thoughtfully discussed whether a severely hypoxic newborn should be intubated immediately or ventilated with bag and mask.A third alternative is mouth-tomouth ventilation. The technique requires skill. The physician stands at the side of the baby's head. His hands must support and lift forward both angles of the baby's mandible. His mouth fits on the baby's opened mouth, with the leak from the baby's nose controlled by pressure from the side of the physician's face. The chest is observed to make sure it rises well during inflation.The physician usually wears a porous surgical mask, but the procedure can be done without an interposed mask. Either way, no time should be lost in starting ventilation.Preliminary suctioning ordinarily is omitted. There is little risk of aspiration, since mucus or meconium in the nasopharynx and nose is blown out
A subpopulation of mouse esophageal basal cells has properties of stem cells with the capacity for self-renewal and lineage specification
Authors: Jiri Kalabis, Kenji Oyama, Takaomi Okawa, Hiroshi Nakagawa, Carmen Z. Michaylira, Douglas B. Stairs, Jose-Luiz Figueiredo, Umar Mahmood, J. Alan Diehl, Meenhard Herlyn, Anil K. Rustgi
Journal: Journal of Clinical Investigation (2008)

The esophageal epithelium is a prototypical stratified squamous epithelium that exhibits an exquisite equilibrium between proliferation and differentiation. After basal cells proliferate, they migrate outward toward the luminal surface, undergo differentiation, and eventually slough due to apoptosis. The identification and characterization of stem cells responsible for the maintenance of the esophageal epithelium remains elusive. Here, we employed Hoechst dye extrusion and BrdU label–retaining assays to identify in mice a potential esophageal stem cell population that localizes to the basal cell compartment. The self-renewing capacity of this population was characterized using a clonogenic assay and a 3D organotypic culture model. The putative esophageal stem cells were also capable of epithelial reconstitution in vivo in direct esophageal epithelial injury models. In both the 3D organotypic culture and direct mucosal injury models, the putative stem cells gave rise to undifferentiated and differentiated cells. These studies therefore provide a basis for understanding the regenerative capacity and biology of the esophageal epithelium when it is faced with injurious insults.
Hashimoto Thyroiditis and Takayasu Aortitis
Authors: George Shih, Wei-Jen Shih, Wen-Sheng Huang, Primo P. Milan
Journal: Clinical Nuclear Medicine (2008)

A woman with Hashimoto thyroiditis, treated with levothyroxine for 4 years, complained of chest pain that radiated to the neck and had progressively worsened for 2 months. CT of the chest showed circumferential thickening of the ascending aorta and aortic arch, compatible with Takayasu arteritis. She underwent F-18 FDG PET imaging, which revealed an abnormal thyroid gland and a ring-like appearance of the mediastinum.
High resolution computed tomography of the lungs
Authors: S. Worthy
Journal: BMJ (1995)

dimensional computer reconstruction of images obtained with x rays and other modalities, and the use of computer systems to enhance, store, and display images.Techniques such as ultrasonography and magnetic resonance imaging that do not use ionising radiation will continue to replace some x ray procedures.New imaging techniques may include infrared imaging and microwave tomography.In radio- therapy, technological improvements will enable the radiation beam to be confined more precisely to the tumour.The benefits of R6ntgen's discovery have been enormous, but there has been a down side.Initially, the dangers associated with the use of x rays were not known, and some of the pioneers received doses of radiation that proved fatal.Tremendous advances in protection against radiation and in reducing doses have taken place over the years and have considerably reduced the dangers from ionising radiation.Although the risks are slight, there should always be a valid clinical indication for any request for an x ray examination.