tbuckley/cabot-search huggingface dataset:
Alu elements shape the primate transcriptome by cis-regulation of RNA editing
Authors: Chammiran Daniel, Gilad Silberberg, Mikaela Behm, Marie Öhman
Journal: Genome biology (2014)

RNA editing by adenosine to inosine deamination is a widespread phenomenon, particularly frequent in the human transcriptome, largely due to the presence of inverted Alu repeats and their ability to form double-stranded structures--a requisite for ADAR editing. While several hundred thousand editing sites have been identified within these primate-specific repeats, the function of Alu-editing has yet to be elucidated.We show that inverted Alu repeats, expressed in the primate brain, can induce site-selective editing in cis on sites located several hundred nucleotides from the Alu elements. Furthermore, a computational analysis, based on available RNA-seq data, finds that site-selective editing occurs significantly closer to edited Alu elements than expected. These targets are poorly edited upon deletion of the editing inducers, as well as in homologous transcripts from organisms lacking Alus. Sequences surrounding sites near edited Alus in UTRs, have been subjected to a lesser extent of evolutionary selection than those far from edited Alus, indicating that their editing generally depends on cis-acting Alus. Interestingly, we find an enrichment of primate-specific editing within encoded sequence or the UTRs of zinc finger-containing transcription factors.We propose a model whereby primate-specific editing is induced by adjacent Alu elements that function as recruitment elements for the ADAR editing enzymes. The enrichment of site-selective editing with potentially functional consequences on the expression of transcription factors indicates that editing contributes more profoundly to the transcriptomic regulation and repertoire in primates than previously thought.
On the Relationship of Crystalline Lecithins to Cholesterol Esterase of Serum
Authors: ARNOLD WAGNER, MARJORIE ZIEBELL
Journal: Circulation Research (1959)

When serum is incubated in the presence of 1-α-dimyristoyl lecithin, the expected disappearance of free cholesterol is greatly enhanced. This effect is not seen in replicate experiments employing two other crystalline lecithins.
Woodchuck hepatitis and hepatocellular carcinoma: Correlation of histologic with virologic observations
Authors: Hans Popper, James W.-K. Shih, John L. Gerin, Doris C. Wong, Bill H. Hoyer, William T. London, David L. Sly, Robert H. Purcell
Journal: Hepatology (1981)

The livers of 33 captive woodchucks were examined histologically in 30 biopsy and 10 autopsy specimens and the findings were correlated with serum determinations for woodchuck hepatitis virus (WHV), surface antigen (WHsAg) and antibody (anti-WHs), and WHV DNA and DNA polymerase. The liver appeared normal in all 3 serum-negative animals, 7 of 16 with indeterminate WHV status, and 1 of 4 with anti-WHs, but not in 10 animals with WHsAg, WHV DNA, and DNA polymerase. Mild hepatic inflammation was found in 7 woodchucks with indeterminate status, 4 with anti-WHs, and 2 with each marker of WHV infection. Significant inflammation was found in 2 of indeterminate status and 4 with every marker, whereas more severe lesions (2 of chronic active type) occurred, almost always in autopsy specimens, in 8 animals with every marker. Eight of 10 animals with all markers had orcein-positive inclusions (Shikata’s technique) and 6 had hepatocellular carcinoma associated with acute and chronic hepatic inflammation and, usually, neoplastic nodules in the noncarcinomatous parenchyma. Features distinguishing the woodchuck lesion from human hepatitis B disease were: association of carcinoma with acute hepatic inflammation (but not with cirrhosis) and DNA polymerase in the serum; transition to carcinoma from neoplastic nodules; conspicuous plasma-cellular reaction of hepatic inflammation, and hematopoietic cells in the tumor. Significant hepatic lesions in the woodchucks were regularly associated with serum WHsAg, WHV DNA, and DNA polymerase. In contrast to man, hepatocellular carcinoma in woodchucks was regularly associated with these markers of active viral replication. The nature of the orcein-positive inclusions requires elucidation, although they may assist in screening for similar viruses in other species. The woodchuck may help in the study of the relation between hepatocellular carcinoma and hepatitis B, including the possibility of cocarcinogenic factors.
Origin, Kinetics, and characteristics of pulmonary macrophages in the normal steady state.
Authors: A B van oud Alblas, R van Furth
Journal: The Journal of Experimental Medicine (1979)

Pulmonary macrophages of mice in the steady state were isolated by lavage with PBS containing EDTA and subsequent enzymatic digestion of tissue with pronase and DNA-ase. By this method, the total pulmonary macrophage population was obtained in two cell suspensions, one with a pure population of pulmonary alveolar macrophages (PAM) and the other with a mixed population of pulmonary alveolar and pulmonary tissue macrophages (PTM). The morphological, cytochemical, and functional characteristics of both PAM and PTM were like those of mature tissue macrophages except for the presence of C3 receptors. These receptors were almost absent on PAM and present on a larger number of cells in the mixed population of PAM and PTM. The total pulmonary macrophage population of mice in the steady state is approximately equal to 2 x 10(6), of which about 93% are PAM and about 7% are PTM. In labeling experiments with 3H-thymidine, the low in vitro labeling indices (less than 3%) for both PAM and the mixture of PAM and PTM, showed that both are essentially nondividing cells. In vivo labeling studies showed an increase in the number of labeled macrophages that can only be attributed to labeled monocytes migrating into the lungs. Additional evidence was provided by a decrease in the labeling indices of pulmonary macrophages when mice were treated with hydrocortisone acetate, which causes a severe monocytopenia, thus preventing monocyte influx into the lungs. Confirmation of the bone marrow origin was obtained in mice labeled after x-irradiation with partial bone marrow shielding: labeled pulmonary macrophages were found in the exposed lungs. In all experiments, the labeling indices were identical in the two macrophage populations isolated. These results show that the influx of monocytes is the source of cell renewal for the pulmonary macrophages. No indications for an interstitial division or maturation compartment in the lung were found. Quantitation of the efflux of labeled monocytes from the blood, and the number of labeled pulmonary macrophages, showed that in the steady state about 15% of the monocytes leaving the circulation become pulmonary macrophages and that the turnover time of pulmonary macrophages is approximately equal to 27 d.
Histone acetylation and deacetylation: importance in inflammatory lung diseases
Authors: P. J. Barnes, I. M. Adcock, K. Ito
Journal: European Respiratory Journal (2005)

Inflammatory lung diseases are characterised by increased expression of multiple inflammatory genes that are regulated by proinflammatory transcription factors, such as nuclear factor-κB. Gene expression is regulated by acetylation of core histones through the action of coactivators, such as CREB-binding protein, with intrinsic histone acetyltransferase (HAT) activity. Conversely, gene repression is mediated via histone deacetylases (HDACs) and other corepressors. In asthma, there is an increase in HAT activity and some reduction in HDAC activity, which is restored by corticosteroid therapy. Corticosteroids switch off inflammatory genes in asthma through the inhibition of HAT activity and by the recruitment of HDAC2 to the activated inflammatory gene complex. In chronic obstructive pulmonary disease, there is a reduction in HDAC2 activity and expression, which may account for the amplified inflammation and resistance to the actions of corticosteroids. The reduction in HDAC2 may be secondary to oxidative and nitrative stress as a result of cigarette smoking and severe inflammation, and may also occur in severe asthma, smoking asthmatic patients and cystic fibrosis. Similar mechanisms may also account for the steroid resistance seen with latent adenovirus infections. The reduction in histone deacetylase activity can be restored by theophylline, which may be able to reverse steroid resistance in chronic obstructive pulmonary disease and other inflammatory diseases.
Electrophysiological Properties of the Canine Peripheral A-V Conducting System
Authors: ROBERT J. MYERBURG, JOHN W. STEWART, BRIAN F. HOFFMAN
Journal: Circulation Research (1970)

Action potential durations and local refractory periods were mapped along the course of canine conducting tissue from bundle branches to the termination of false tendons in ventricular muscle. Standard microelectrode techniques were used. Areas of maximum action potential duration, which coincided with areas of maximum local refractory periods, were consistently found 2 to 3 mm proximal to the termination of conducting fibers in muscle. The refractory periods at the areas of maximum action potential duration were quantitatively identical in the multiple false tendons of a segment of the conducting system, providing a uniform functional limit for the propagation of premature impulses across the distal end of the conducting system of the segments studied. It was demonstrated that appropriately timed premature impulses could be confined within conducting tissue either proximal or distal to the area of maximum action potential duration. This occurred when the area of maximum duration was still refractory, after other areas of the conducting system had recovered excitability. In most preparations, maximum action potential durations and functional refractory periods across distal false tendons were longer in tissue from the right side than from the left side of the conducting system.
<i>Interleukin‐13</i> promoter gene polymorphism ‐1112C/T is associated with the systemic form of mastocytosis
Authors: B. Nedoszytko, M. Niedoszytko, M. Lange, J. Van Doormaal, J. Gleń, M. Zabłotna, J. Renke, A. Vales, F. Buljubasic, E. Jassem, J. Roszkiewicz, P. Valent
Journal: Allergy (2009)

Mastocytosis is a heterogenous disease involving mast cells (MC) and their progenitors. Cutaneous and systemic variants of the disease have been reported. In contrast to cutaneous mastocytosis (CM), patients with systemic mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage haematopoietic neoplasm. Little is known, however, about factors predisposing for the development of SM. One factor may be cytokine regulation of MC progenitors.We examined the role of the interleukin-13 (IL-13) promoter gene polymorphism -1112C/T, known to be associated with increased transcription, in mastocytosis using allele-specific polymerase chain reaction method. Serum tryptase and IL-13 levels were determined by immunoassay, and expression of the IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain reaction and flow cytometry.The frequency of the -1112T allele of the IL-13 promoter was significantly higher in patients with SM compared with CM (P < 0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001). Correspondingly, the polymorphism was found to correlate with an elevated serum tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both of which are almost invariably associated with SM. Serum IL-13 levels were also higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC carriers (P < 0.05). Finally, we were able to show that neoplastic human MC display IL-13 receptors and grow better in IL-13-containing medium.The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.
Ascertainment Biases in SNP Chips Affect Measures of Population Divergence
Authors: A. Albrechtsen, F. C. Nielsen, R. Nielsen
Journal: Molecular Biology and Evolution (2010)

Chip-based high-throughput genotyping has facilitated genome-wide studies of genetic diversity. Many studies have utilized these large data sets to make inferences about the demographic history of human populations using measures of genetic differentiation such as F(ST) or principal component analyses. However, the single nucleotide polymorphism (SNP) chip data suffer from ascertainment biases caused by the SNP discovery process in which a small number of individuals from selected populations are used as discovery panels. In this study, we investigate the effect of the ascertainment bias on inferences regarding genetic differentiation among populations in one of the common genome-wide genotyping platforms. We generate SNP genotyping data for individuals that previously have been subject to partial genome-wide Sanger sequencing and compare inferences based on genotyping data to inferences based on direct sequencing. In addition, we also analyze publicly available genome-wide data. We demonstrate that the ascertainment biases will distort measures of human diversity and possibly change conclusions drawn from these measures in some times unexpected ways. We also show that details of the genotyping calling algorithms can have a surprisingly large effect on population genetic inferences. We not only present a correction of the spectrum for the widely used Affymetrix SNP chips but also show that such corrections are difficult to generalize among studies.
Cancer in global health: How do prevention and early detection strategies relate?
Authors: André M. Ilbawi, Benjamin O. Anderson
Journal: Science Translational Medicine (2015)

National cancer control plans are needed to stem the rapidly rising global cancer burden. Prevention and early detection are complementary but distinct strategies for cancer control. Some cancers are prevented through behavior and/or environmental modifications that reduce cancer risk, whereas other cancers are more amenable to treatment when they are successfully diagnosed at early stages. Prevention and early detection strategies should be prioritized on the basis of country-specific cancer demographics, modifiable risk factor distribution, and existing treatment resource availability. Following an individualized plan integrating prevention and early detection strategies, deficits can be targeted to strengthen national health systems for cancer control.
Acute lymphocytic leukemic transformation of chronic lymphocytic leukemia: Substantiation by flow cytometry
Authors: Eugene P. Frenkel, Frances S. Ligler, Mateel S. Graham, Jose A. Hernandez, John R. Kettman, R. Graham Smith
Journal: American Journal of Hematology (1981)

Abstract Acute leukemia, during the course of chronic lymphocytic leukemia, is a rare event and only a small fraction of such cases have been shown to be true transformations to acute lymphocytic leukemia. In one previous case, evidence suggested this was transformation of a single neoplastic clone. The present report describes the clinical and laboratory findings in a case of chronic lymphocytic leukemia in which an acute leukemic pattern evolved. The fluorescence‐activated cell sorter provided the resolution needed to distinguish low numbers of surface immunoglobulins on the acute leukemic cells, verifying their identity as B lymphoblasts. Furthermore, a small population of large cells bearing the same light chain type as the acute leukemic cells were detected in the spleen 3½ months before clinical or laboratory evidence of the onset of the acute leukemia.
Does Size Matter?
Authors: Frederick E. Dewey, David Rosenthal, Daniel J. Murphy, Victor F. Froelicher, Euan A. Ashley
Journal: Circulation (2008)

Extensive evidence is available that cardiovascular structure and function, along with other biological properties that span the range of organism size and speciation, scale with body size. Although appreciation of such factors is commonplace in pediatrics, cardiovascular measurements in the adult population, with similarly wide variation in body size, are rarely corrected for body size. In this review, we describe the critical role of body size measurements in cardiovascular medicine. Using examples, we illustrate the confounding effects of body size. Current cardiovascular scaling practices are reviewed, as are limitations and alternative relationships between body and cardiovascular dimensions. The experimental evidence, theoretical basis, and clinical application of scaling of various functional parameters are presented. Appropriately scaled parameters aid diagnostic and therapeutic decision making in specific disease states such as hypertrophic cardiomyopathy and congestive heart failure. Large-scale studies in clinical populations are needed to define normative relationships for this purpose. Lack of appropriate consideration of body size in the evaluation of cardiovascular structure and function may adversely affect recognition and treatment of cardiovascular disease states in the adult patient.
Romanian GPs to take control of their practices
Authors: T. Toma
Journal: BMJ (1999)

The Romanian government will be giving some GPs responsibil-ity for the practices where they currently work, Mr Hajdu Gabor, the state secretary of health, has announced. GPs who have worked in their practices for a certain number of years will be offered the new arrangement.

Starting in September 1999 the GPs will have to sign a renting …
Association of Depressive Syndrome and Early Deaths Among Patients After Stem-Cell Transplantation for Malignant Diseases
Authors: Fausto R. Loberiza, J. Douglas Rizzo, Christopher N. Bredeson, Joseph H. Antin, Mary M. Horowitz, Jane C. Weeks, Stephanie J. Lee
Journal: Journal of Clinical Oncology (2002)

PURPOSE: The association of depression and increased mortality in the general population, and also various medical conditions, is well documented. However, depression is not well studied in the setting of hematopoietic stem-cell transplantation (HSCT). We examined the association between depressive syndrome and survival after HSCT. PATIENTS AND METHODS: A total of 193 patients who received autologous or allogeneic HSCT from Brigham and Women’s Hospital or Dana-Farber Cancer Institute were evaluated prospectively. The self-rated Likert-scaled symptom checklist, the SF-36, and the Spitzer Quality of Life Index Scale were administered. Outcomes evaluated included survival and quality of life. RESULTS: Sixty-seven patients (35%) satisfied the criteria for depressive syndrome. The 1-year probability of survival for the depressed and nondepressed patients was 85% (95% confidence interval [CI], 74% to 92%) and 94% (95% CI, 89% to 97%), respectively (P = .04). In multivariable modeling, depressed patients have a three-fold greater risk of dying than nondepressed patients (95% CI, 1.07 to 8.30; P = .04) between 6 and 12 months after HSCT after adjusting for other prognostic factors. Global inferiority in quality of life was observed in the depressed cohort when last measured at 24 months after transplantation. CONCLUSION: Depressive syndrome after HSCT is associated with decreased survival, at least from 6 to 12 months after transplantation. Persistence of this association after controlling for possible confounding factors suggests that depression may be more than simply a marker for concurrent ill health. This study raises an interesting hypothesis as to whether psychological or pharmacologic intervention for depression after HSCT can improve survival and/or quality of life.
Socioeconomic status and race as risk factors for cockroach allergen exposure and sensitization in children with asthma
Authors: Sampson B. Sarpong, Robert G. Hamilton, Peyton A. Eggleston, N.Franklin Adkinson
Journal: Journal of Allergy and Clinical Immunology (1996)

The domestic cockroach has been identified as an important source of indoor aeroallergens worldwide in both temperate and tropical climates. Because cockroach populations are highest in crowded urban areas, some have suggested that the increased asthma morbidity and mortality rates in inner cities could be related in part to cockroach allergen exposure. We have examined cockroach allergen exposure in the homes of children with asthma in both urban and suburban locations and have related the rates of exposure and sensitization to socioeconomic, racial, and demographic factors.The study was designed to determine the independent contribution of race, socioeconomic status, and place of residence to the risk of cockroach allergen exposure and sensitization in children with asthma.Eighty-seven children with moderate to severe allergic asthma, aged 5 to 17 years, participating in a prospective trial of immunotherapy, were evaluated. Extracted dust samples from three home locations were analyzed by using two-site monoclonal immunoassays for major cockroach allergens (Bla g 1 and Bla g 2). A puncture skin test with a mixed cockroach allergen extract was performed in 81 of the 87 subjects.In the 87 homes evaluated, 26% of the bedroom dust samples had detectable levels of cockroach allergen. In homes with detectable bedroom cockroach allergen levels, mean Bla g 1 and Bla g 2 concentrations in urban and suburban homes were similar. Over 80% of children with bedroom Bla g 1 or Bla g 2 of 1 U/gm or greater demonstrated skin sensitivity to cockroach allergen. The rate of cockroach sensitization was directly related to the level of bedroom exposure. African-American race was the only factor that was independently associated with cockroach allergen exposure (p = 0.05). Lower socioeconomic status, age greater than 11 years, cockroach exposure, and African-American race were all independently associated with cockroach allergen sensitization on the basis of stepwise multiple linear regression analysis.African-American race and low socioeconomic status were both independent, significant risk factors for cockroach allergen sensitization in children with atopic asthma. Cockroach allergen is detectable throughout the house, including the critical bedroom environment.
Medial Thickness of Pulmonary Trunk in Rats with Cor Pulmonale induced by Ingestion of Crotalaria spectabilis Seeds
Authors: D. Heath, J. M. Kay
Journal: Cardiovascular Research (1967)

Medial hypertrophy of the pulmonary trunk is known to occur in man as a response to pulmonary hypertension, but it has never been demonstrated that this change can be produced experimentally in animals. In the present study pulmonary hypertension was induced in 10 rats by feeding them a diet which included 0·1% ground Crotalaria spectabilis seeds, which contain monocrotaline. The animals died after being on this diet for between 36 and 60 days. Thirteen control animals were also studied. All the test rats showed increased medial thickness of the pulmonary trunk (within one month) and there was a comparable increase of right ventricular weight and medial thickness of the small pulmonary arteries.