tbuckley/cabot-search huggingface dataset:
Exploring Massive Incomplete Lineage Sorting in Arctoids (Laurasiatheria, Carnivora)
Authors: Liliya Doronina, Gennady Churakov, Jingjing Shi, Jürgen Brosius, Robert Baertsch, Hiram Clawson, Jürgen Schmitz
Journal: Molecular Biology and Evolution (2015)

Freed from the competition of large raptors, Paleocene carnivores could expand their newly acquired habitats in search of prey. Such changing conditions might have led to their successful distribution and rapid radiation. Today, molecular evolutionary biologists are faced, however, with the consequences of such accelerated adaptive radiations, because they led to sequential speciation more rapidly than phylogenetic markers could be fixed. The repercussions being that current genealogies based on such markers are incongruent with species trees.Our aim was to explore such conflicting phylogenetic zones of evolution during the early arctoid radiation, especially to distinguish diagnostic from misleading phylogenetic signals, and to examine other carnivore-related speciation events. We applied a combination of high-throughput computational strategies to screen carnivore and related genomes in silico for randomly inserted retroposed elements that we then used to identify inconsistent phylogenetic patterns in the Arctoidea group, which is well known for phylogenetic discordances.Our combined retrophylogenomic and in vitro wet lab approach detected hundreds of carnivore-specific insertions, many of them confirming well-established splits or identifying and solving conflicting species distributions. Our systematic genome-wide screens for Long INterspersed Elements detected homoplasy-free markers with insertion-specific truncation points that we used to distinguish phylogenetically informative markers from conflicting signals. The results were independently confirmed by phylogenetic diagnostic Short INterspersed Elements. As statistical analysis ruled out ancestral hybridization, these doubly verified but still conflicting patterns were statistically determined to be genomic remnants from a time of ancestral incomplete lineage sorting that especially accompanied large parts of Arctoidea evolution.
Canine myocardial creatine kinase isoenzymes after chronic coronary artery occlusion.
Authors: S W Sharkey, M M Murakami, S A Smith, F S Apple
Journal: Circulation (1991)

BACKGROUND Creatine kinase (CK) exists as three cytosolic isoenzymes, CK-MM, CK-MB, and CK-BB, and one mitochondrial isoenzyme. Animal and human observations suggest that the CK-MB content of myocardium is dynamic and may increase in response to ischemia, but the response of the myocardial CK system to chronic coronary artery occlusion is not well-defined. METHODS AND RESULTS We measured serial changes in myocardial total CK, percent CK-MB, and percent CK-BB before and 3 weeks after coronary artery occlusion in 17 pentobarbital-anesthetized dogs. Tissue biopsies were obtained from the left anterior descending (LAD) coronary artery myocardium, the right coronary artery (RCA) myocardium, and the circumflex coronary artery myocardium at baseline and 3 weeks after LAD occlusion (n = 6), RCA occlusion (n = 5), and no coronary artery occlusion (n = 6). Tissue samples were assayed for total CK, percent CK-MB, and percent CK-BB. Samples were also examined by electron microscopy for evidence of ischemic myopathy. Total myocardial CK activity did not change over 3 weeks. Percent CK-MB increased significantly in the tissue supplied by the occluded artery (4.1-fold in dogs with LAD occlusion and 6.7-fold in dogs with RCA occlusion). Percent CK-BB did not change. Dogs with LAD occlusion had ultrastructural evidence of myopathic fibers interspersed with normal fibers in the LAD myocardium. Dogs with RCA occlusion had no ultrastructural evidence of myopathic fibers in the RCA myocardium. CONCLUSIONS Chronic coronary artery occlusion causes a pronounced change in the canine myocardial CK system that is limited to the tissue supplied by the occluded coronary artery. These biochemical alterations do not correlate with any cellular ultrastructural changes. Myocardial CK-MB content is dynamic, varies geographically within the heart, and increases rapidly after coronary artery occlusion.
A substantial cause of preventable illness
Authors: Jerry Avorn, William H Shrank
Journal: BMJ (2008)

Doctors should pay greater attention to managing the risk-benefit relationship to improve care of patients over 65, urge <b>Jerry Avorn</b> and <b>William Shrank</b>. The challenge of safer prescribing, says <b>Anne Spinewine</b> (doi: 10.1136/bmj.39520.686458.94), lies in shared decision making
Enhanced expression of Fas ligand (FasL) in fibrotic interstitial lung diseases (ILDs). The possible role of membrane-bound FasL form
Authors: Piotr Kopinski, Andrzej Dyczek, Barbara Balicka-Slusarczyk, Grzegorz Przybylski, Joanna Chorostowska-Wynimko, Adam Szpechcinski, Teresa Iwaniec, Karina Szablowska, Jerzy Szczeklik
Journal: European Respiratory Journal (2011)

Background: The exact role of FasL and particularly its soluble and membrane-bound form in the development of chronic ILDs and lung fibrosis has not been extensively explored.

Methods: We aimed at analyzing membrane-bound FasL expression on alveolar macrophages (AM) and lymphocytes (AL) as well as soluble FasL (sFasL) levels in bronchoalveolar lavage (BAL) from ILDs patients: pulmonary sarcoidosis (PS), hypersensitivity pneumonitis (HP), silicosis, asbestosis, idiopathic pulmonary fibrosis (IPF), nonspecific interstitial pneumonia (NSIP), and healthy subjects (n=89,12,7,8,23,6,17, resp.).

Results: In IPF significantly increased percentage of AM FasL+ and CD8+FasL+ cells as well as sFasL levels in BAL were found. Increased sFasL levels were also observed in HP. NSIP and asbestosis were characterized by higher AM FasL+ relative number; CD8+FasL+ population was expanded in asbestosis only. There was significant decline in AL FasL+ percentage in PS and HP. Systemic steroid treatment, assessed in PS and IPF subgroups, did not affect FasL expression. Smokers with ILD tended to present lower sFasL levels, but not BAL cell FasL+ numbers. Vital capacity was negatively correlated with sFasL levels, AM FasL+ and CD8+FasL+ cell relative count. CD4+FasL+ and CD8+FasL+ percentage strongly correlated with BAL neutrophilia, an unfavourable prognostic factor of lung fibrosis.

Conclusions: The concurrent comparative BAL analysis for FasL expression indicates that FasL+ AM and AL (especially Tc cells) comprise an important element of the fibrotic process, mostly in IPF. FasL might play a crucial role in other fibrosis-complicated ILDs, like NSIP and asbestosis.
Increased Frequency of a Unique Spleen Tyrosine Kinase Bright Memory B Cell Population in Systemic Lupus Erythematosus
Authors: Sarah J. Fleischer, Claudia Giesecke, Henrik E. Mei, Peter E. Lipsky, Capucine Daridon, Thomas Dörner
Journal: Arthritis & Rheumatology (2014)

Systemic lupus erythematosus (SLE) is characterized by B cell hyperactivity and autoantibody production. As spleen tyrosine kinase (Syk) is pivotal in B cell activation, these experiments aimed to examine the extent to which Syk was abnormally expressed in SLE B cells and the nature of the B cell subset that differently expressed Syk.B cells from healthy donors and SLE patients were analyzed by flow cytometry to assess basal expression of Syk and phosphorylated Syk. B cell subsets expressing higher levels of Syk were found, and their detailed phenotype, in vitro differentiation into plasmablasts/plasma cells, and Syk induction by cytokines were determined.Syk expression was higher in CD27+ memory B cells than in naive B cells from SLE patients. However, a significantly increased frequency of CD27- B cells with bright expression of Syk (Syk++) was found in SLE patients. CD27-Syk++ B cells showed enhanced basal expression of p-Syk and stronger Syk phosphorylation upon B cell receptor (BCR) engagement as compared to CD27-Syk+ B cells. CD27-Syk++ B cells were CD38- as well as CD19++, CD20++, and mainly CD21-, with decreased ABCB1 transporter activity. In contrast to CD27-Syk+ B cells, CD27-Syk++ B cells exhibited enhanced differentiation into CD27++ IgG-secreting cells and expressed somatically mutated BCR gene rearrangements. Syk++ B cells were inducible in vitro by stimulation with interferon-γ, lipopolysaccharide, or tumor necrosis factor α.SLE patients exhibit an increased frequency of hitherto unknown CD27-Syk++ memory-like B cells, indicating that intracellular Syk density could distinguish CD27- memory B cells from truly naive B cell subsets. Furthermore, the CD27-Syk++ subset is a candidate for a source of increased plasma cells in SLE.
Aerosol Insulin Induces Regulatory CD8 γδ T Cells That Prevent Murine Insulin-dependent Diabetes
Authors: Leonard C. Harrison, Majella Dempsey-Collier, David R. Kramer, Kazuma Takahashi
Journal: The Journal of Experimental Medicine (1996)

Cellular immune hyporesponsiveness can be induced by the presentation of soluble protein antigens to mucosal surfaces. Most studies of mucosa-mediated tolerance have used the oral route of antigen delivery and few have examined autoantigens in natural models of autoimmune disease. Insulin is an autoantigen in humans and nonobese diabetic (NOD) mice with insulindependent diabetes mellitus (IDDM). When we administered insulin aerosol to NOD mice after the onset of subclinical disease, pancreatic islet pathology and diabetes incidence were both significantly reduced. Insulin-treated mice had increased circulating antibodies to insulin, absent splenocyte proliferation to the major epitope, insulin B chain amino acids 9–23, which was associated with increased IL-4 and particularly IL-10 secretion, and reduced proliferation to glutamic acid decarboxylase, another islet autoantigen. The ability of splenocytes from insulin-treated mice to suppress the adoptive transfer of diabetes to nondiabetic mice by T cells of diabetic mice was shown to be caused by small numbers of CD8 γδ T cells. These findings reveal a novel mechanism for suppressing cell-mediated autoimmune disease. Induction of regulatory CD8 γδ T cells by aerosol insulin is a therapeutic strategy with implications for the prevention of human IDDM.
Kinetic Studies on the Hepatic Microsomal Metabolism of Dimethylnitrosamine, Diethylnitrosamine, and Methylethylnitrosamine in the Rat&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Irene Y. Chau, Doron Dagani, Michael C. Archer
Journal: JNCI Journal of the National Cancer Institute (1978)

The oxidative dealkylation of dimethylnitrosamine (DMN), diethylnitrosamine (DEN), and methylethylnitrosamine (MEN) by Sprague-Dawley rat liver microsomes was studied by a colorimetric assay for the simultaneous analysis of formaldehyde and acetaldehyde. Dealkylation in each instance followed Michaelis-Menten kinetics, but the Michaelis constant (Km) for DEN was an order of magnitude smaller than the Km for DMN. Km values for demethylation and deethylation of MEN were intermediate between those for DMN and DEN. DMN inhibited-deethylase, and DEN inhibited DMN-demethylase activity. The inhibition was of a mixed type in both instances.
Heparin Effect on DNA Synthesis in a Murine Fibrosarcoma Cell Line: Influence of Anionic Density&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: M W Piepkorn, R A Daynes
Journal: JNCI Journal of the National Cancer Institute (1983)

The effects of heparin subfractions on DNA synthesis in a murine cutaneous fibrosarcoma cell line were examined. Porcine mucosal heparin was preparatively fractionated for anionic charge density by DEAE-Sephadex chromatography and for molecular weight by Sephadex G-100 filtration. The cell line was plated from confluent monolayer cultures and grown in medium and fetal bovine serum, with or without a heparin fraction at a final concentration of 10 micrograms/ml. At intervals thereafter, the cells were pulsed with [3H]thymidine. A low-charge density heparin fraction stimulated [3H]thymidine incorporation (cpm/mg protein and cpm/cell) during the first 3 days of growth compared to control values without added heparin, whereas a high-charge density heparin fraction had little of this effect (186 +/- 35% of control vs. 101 +/- 14%, respectively; P less than .05). The augmentation of DNA synthesis observed with the low-charge density fraction correlated with increased proportions of cells in S and G2 phases compared with those of the controls, as determined by flow cytofluorometry. Low- and high-molecular-weight heparin fractions did not significantly alter DNA synthesis. Heparin subfractions are thus heterogeneous with respect to their effect on cellular DNA synthesis in this tumor line.
In Vitro Induction of Tumor-Specific Immunity. II. Activation of Cytotoxic Lymphocytes to Murine Oncofetal Antigens23
Authors: Stanley E. Chism, Robert C. Burton, Noel L. Warner
Journal: JNCI Journal of the National Cancer Institute (1976)

The presence of oncofetal antigens (OFA) on a wide variety of murine tumor cells was demonstrated by a totally in vitro system of cellular immunity. Nonimmune spleen lymphocytes were cocultivated with Irradiated syngeneic fetal liver cells and, at various times after initiation of culture, were tested for the presence of cytotoxic lymphocytes (CL) by 51Cr-release assay with labeled tumor target cells. Significant cytotoxic activity was regularly detected after such culture, whereas only minor levels appeared in control cultures of spleen lymphocytes with irradiated syngeneic spleen cells. Specificity of the reaction was assessed by inhibition tests in which nonlabeled cells were ad-mixed to the Cl and 51Cr-labeled tumor targets. Fetal liver cells gave significant Inhibition; however, no Inhibition was found with adult spleen cells. Various tumor types gave inhibition, and fibro-sarcomas were more effective than plasmacytomas or lymphomas. The results suggested that all tumor types tested possess such OFA, as well as their unique or virus-associated, tumor-associated transplantation antigens, and that the in vitro system permits a more active response to the tumor-associated OFA than that observed in in vivo studies.
Nontuberculous mycobacterial disease of the lungs in North-West region of Russia
Authors: Viacheslav Zhuravlev, Tatiayna Otten, Nataliya Melnikova, Ludmila Archakova, Pavel Gavrilov, Marina Shulgina
Journal: European Respiratory Journal (2014)

The incidence of (NTM) as human pathogens is increasing. There are no any statistical data for the incidence of NTM detection. Definitive diagnoses of pulmonary NTM infection are difficult. 450 NTM cultures were isolated from 359 patients with TB suspicion using solid media and/or BACTEC MGIT 960 (2011-13 years). Primary screening of cultures was performed using standard microbiological techniques blood agar culture and ZN stain. For suspected samples species identification using GenoTypeCM/AS (HAIN Lifescience, Germany) were carried out. Following spectra of NTM strains were detected: M.avium (240 strains 53.3%), M.intracellulare 39(8.6%), M.fortuitum 38(8.4%), M.chelonae 38(8.4%), M.abscessus 23( 5.1%), M.peregrinum 19(4.2%), M.lentiflavum 19(4.2%), M.gordonae15(3.3%), M.kansasii 5(1.1%), M.malmoense 5(1.1%), M.xenopi 3(0.6%), M.celatum 3(0.6%), M.scrofulacium 2(0.4% ), M.simiae 1(0.2%). The clinical symptoms of NTM pulmonary disease was variable and nonspecific. The clinical presentation frequently included fever, cough, weight loss, night sweats, hemoptysis, and dyspnea have been revealed only at 102 (28.4%) patients. 38 patients (10.6%) had HIV co infection. Pulmonary infiltrates were the most common (57.4%), disseminated forms (42.6%). The location was unilateral in 53.5% and affection in upper lobes was observed in 79.5% cases.

Conclusions:The most common NTM specie in our area is M.avium. Pulmonary disease by NTM has a clinical and radiological presentation similar to tuberculosis. Usage of exact and rapid molecular-genetic method - GenoTypeCM/AS helps to perform accuracy species identification of NTM, it helps physicians to ensure accurate diagnosis and prescribe adequate treatment.
Diagnostic yield of flexible bronchoscopy: A retrospective study over six months
Authors: Anna Werpachowska, Tania Kakoudaki, Shoaib Faruqi
Journal: European Respiratory Journal (2014)

Flexible bronchoscopy is a common invasive procedure performed for diagnostic or therapeutic purposes. In this study we assess the diagnostic yield of routine bronchoscopic procedures.  Methods: Data from consecutive flexible bronchoscopic procedures performed at our University Hospital over a period of 6 months were analyzed retrospectively using procedure reports and computerized patient information system. The yield of diagnostic procedures analysed included mucosal bronchial biopsies, bronchial washings and bronchial brushings. To estimate diagnostic yield the final conclusion based on all available investigations was used.  Results: Of 149 procedures (male 55%, mean age 65 yrs) 78 were for suspected lung cancer, 34 for haemoptysis and 37 for other indications such as cavitating lung lesions, infection in an immune compromised patient and chronic cough. The overall diagnostic yield was 76.9%. Bronchoscopy performed for suspected lung cancer confirmed malignancy in 52.6%. This increased to 80% if an occlusive tumour was seen. In the 66 cases of confirmed lung cancer bronchial biopsy was performed in 38. Of this 6 were not diagnostic and in these 1 case was diagnosed by both wash and brush and 1 by only brush, the rest being non-diagnostic on bronchoscopy. In 25 cases where biopsies were not done brush or wash was diagnostic in 12. None of the procedures done for haemoptysis with normal radiological imaging demonstrated significant pathology. No significant complications were documented.  Conclusions: We confirm that bronchoscopic samplings are safe and have a high diagnostic yield. We also demonstrate the importance of bronchial washings and brushings to increase the diagnostic yield in lung cancer.
Celebrating the ACP Centennial: From the <i>Annals</i> Archive—Cervical Cancer Screening
Authors: Deborah Cotton
Journal: Annals of Internal Medicine (2015)

Editorials16 June 2015Celebrating the ACP Centennial: From the Annals Archive—Cervical Cancer ScreeningDeborah Cotton, MD, MPH, Deputy EditorDeborah Cotton, MD, MPH, Deputy EditorSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M15-0760 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail During the 2015 centennial year of the American College of Physicians, publisher of Annals of Internal Medicine, Annals editors will link an article in each issue with an earlier paper from our archives addressing the same disease or clinical question. We hope our readers find this interesting and we welcome comments, especially from physicians who were practicing at the time of publication of the original paper who might offer insight into the impact of the earlier paper on their knowledge or practice.In this issue, Sawaya and colleagues (1) summarize current evidence for the benefits and harms of periodic cervical ...References1. Sawaya GF, Kulasingam S, Denberg TD, Qaseem A; Clinical Guidelines Committee of the American College of Physicians. Cervical cancer screening in average-risk women: best practice advice from the Clinical Guidelines Committee of the American College of Physicians. Ann Intern Med. 2015;162:851-9. doi:10.7326/M14-2426 LinkGoogle Scholar2. Papanicolaou GN. A survey of the actualities and potentialities of exfoliative cytology in cancer diagnosis. Ann Intern Med. 1949;31:661-74. doi:10.7326/0003-4819-31-4-661 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoA SURVEY OF THE ACTUALITIES AND POTENTIALITIES OF EXFOLIATIVE CYTOLOGY IN CANCER DIAGNOSIS GEORGE N. PAPANICOLAOU Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians George F. Sawaya , Shalini Kulasingam , Thomas D. Denberg , Amir Qaseem , and Cervical Cancer Screening in Average-Risk Women: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians George F. Sawaya , Shalini Kulasingam , Thomas D. Denberg , Amir Qaseem , and Metrics 16 June 2015Volume 162, Issue 12Page: 868KeywordsArchivesCancer screeningCell biologyCervical cancerCervical cancer screeningCervixDeath ratesLesions ePublished: 16 June 2015 Issue Published: 16 June 2015 Copyright & PermissionsCopyright © 2015 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Intrapulmonary asbestos concentrations in shipyard workers exposed to asbestos in El Ferrol, Spain
Authors: Carmen Diego, Maria Isabel Velasco-García, Maria Jesús Cruz, Uxío Calvo, Rafael de los Reyes, Maria José Mejuto, Jesús Moreno, Jaume Ferrer
Journal: European Respiratory Journal (2011)

Introduction: Asbestos has been used in almost all industrial sectors so the collection of work history data can be difficult. For this reason, quantitative analysis of asbestos bodies (AB) in lung tissue seems more sensitive indicator of exposure than standard questionnaires about exposure to asbestos.

Material and methods: Quantitative analysis was carried out on 31 lung samples of shipyard workers from El Ferrol, Spain with a history of occupational exposure to asbestos, obtained at autopsy, in order to ascertain the concentration of AB (expressed in AB/g of dry tissue) in the lungs. This analysis was carried out in accordance with the guidelines for the analysis of mineral fibres in biological samples set by De Vuyst et al, ERS Working Group. Observation period: 1/1/2008 to October 2010.

Results: 12 had pulmonary adenocarcinoma, 5 epidermoid carcinoma, 1 poorly differentiated carcinoma, 4 asbestosis, 5 mesothelioma, 2 pleural plaques and 2 did not have pathologies related to asbestos exposure. All but one of the patients had a concentration of over 1000 AB/g in dry tissue. The average AB/g was 5947 (range:249-4660059). The work history of 29 patients was collected; 27 had worked in naval shipyards. Average age at death: 67.5. A detailed work history was not collected for 8 patients. Average period of exposure: 24.21 years. 26 patients (83.8%) had been smokers with an average consumption of 26 cigarettes/day.

Conclusions: The quantification of AB in pulmonary tissue is a very useful tool to evaluate the history of exposure to asbestos. The shipyard workers from el Ferrol had a very high concentration of AB in the lung that are the cause of the pathology.
Brief Communication: In Vitro Inhibition of Cell-Mediated Cytotoxicity Against Syngeneic Friend Virus-Induced Leukemia by Immunoregulatory Alpha Globulin
Authors: Moshe Glaser, Chou-Chik Ting, Ronald B. Herberman
Journal: JNCI Journal of the National Cancer Institute (1975)

Immunoregulatory alpha-globulin (IRA) derived from normal human plasma decreased cytotoxic reactivity as measured by an in vitro 5-iodo-2'-deoxyridine release assay of immune mouse lymphocytes against the syngeneic Friend virus-induced leukemia, FBL-3. This inhibitory effect depended on the dose of IRA used and was not due to the cytotoxic effects of IRA on the effector cells or target tumor cells. We also found elevated levels of serum alpha-gloubins in FBL-3 tumor-bearing mice as compared to normal mice. These data and the demonstration of decreased specific cytotoxic reactivity in FBL-3 tumor-bearing mice suggest that IRA functions in the suppression of the host's immune response against tumors.