tbuckley/cabot-search huggingface dataset:
Quantitative Prediction of Molecular Clock and Ka/Ks at Short Timescales
Authors: G. I. Peterson, J. Masel
Journal: Molecular Biology and Evolution (2009)

Recent empirical studies of taxa including humans, fish, and birds have shown elevated rates of molecular evolution between species that diverged recently. Using the Moran model, we calculate expected divergence as a function of time. Our findings suggest that the observed phenomenon of elevated rates at short timescales is consistent with standard population genetics theory. The apparent acceleration of the molecular clock at short timescales can be explained by segregating polymorphisms present at the time of the ancestral population, both neutral and slightly deleterious, and not newly arising slightly deleterious mutations as has been previously hypothesized. Our work also suggests that the duration of the rate elevation depends on the effective population size, providing a method to correct time estimates of recent divergence events. Our model concords with estimates of divergence obtained from African cichlid fish and humans. As an additional application of our model, we calculate that K(a)/K(s) is elevated within a population before decaying slowly to its long-term value. Similar to the molecular clock, the duration and magnitude of K(a)/K(s) elevation depend on the effective population size. Unlike the molecular clock, however, K(a)/K(s) elevation is caused by newly arising slightly deleterious mutations. This elevation, although not as severe in magnitude as had been previously predicted in models neglecting ancestral polymorphism, persists slightly longer.
Transesophageal echocardiographically facilitated early cardioversion from atrial fibrillation using short-term anticoagulation: Final results of a prospective 4.5-year study
Authors: Warren J. Manning, David I. Silverman, Craig S. Keighley, Peter Oettgen, Pamela S. Douglas
Journal: Journal of the American College of Cardiology (1995)

We sought to validate the safety of transesophageal echocardiographically guided early cardioversion in conjunction with short-term anticoagulation as a strategy for guiding early cardioversion in hospitalized patients with atrial fibrillation. Because atrial thrombi are poorly seen by conventional imaging techniques, several weeks of prophylactic anticoagulation is routinely prescribed before cardioversion. Transesophageal echocardiography is a superior test for identifying atrial thrombi; preliminary feasibility studies have supported its use to guide early cardioversion for patients in whom no thrombus is observed, but safety has not been validated in any large series. All patients admitted to hospital with atrial fibrillation during a 4.5-year period were screened. The inclusion criterion was a clinical duration of atrial fibrillation >2 days or of unknown duration. Patients received anticoagulation with heparin/warfarin and underwent conventional transthoracic echocardiography followed by transesophageal study. Patients in whom transesophageal echocardiography revealed no atrial thrombus underwent pharmacologic or electrical cardioversion followed by warfarin therapy for 1 month. Cardioversion was deferred in patients with evidence of atrial thrombi, and they received prolonged warfarin treatment. Two hundred thirty-three patients (86% of those eligible) agreed to participate, and 230 underwent transesophageal echocardiography. Transesophageal echocardiography identified 40 atrial thrombi (left atrium 34, right atrium 6) in 34 patients (15%). One hundred eighty-six (95%) of 196 patients without thrombi had successful cardioversion to sinus rhythm, all without prolonged anticoagulation, and none (0%, 95% confidence interval 0% to 1.6%) experienced a clinical thromboembolic event. Eighteen patients with atrial thrombi underwent uneventful cardioversion after prolonged anticoagulation. Compared with smaller series that have shown only feasibility, this large prospective and consecutive study of patients undergoing transesophageal echocardiographically facilitated early cardioversion in conjunction with short-term anticoagulation validates the safety of this strategy. This treatment algorithm has a safety profile similar to conventional therapy and minimizes both the period of anticoagulation and the overall duration of atrial fibrillation.
Serum α2 globulin levels in granuloma annulare and necrobiosis lipoidica
Authors: B.B.J. MAJEWSKI, S. BARTER, E.L. RHODES
Journal: British Journal of Dermatology (1981)

Journal Article Serum α2 globulin levels in granuloma annulare and necrobiosis lipoidica Get access B.B.J. MAJEWSKI, B.B.J. MAJEWSKI Department of Dermatology, St Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar S. BARTER, S. BARTER Department of Dermatology, St Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar E.L. RHODES E.L. RHODES Department of Dermatology, St Helier Hospital, Carshalton, Surrey Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 105, Issue 5, 1 November 1981, Pages 557–562, https://doi.org/10.1111/j.1365-2133.1981.tb00799.x Published: 01 November 1981 Article history Accepted: 30 December 1980 Published: 01 November 1981
Functional Inhibition of Constitutive Nitric Oxide Synthase in a Rat Model of Sepsis
Authors: Jeremy A. Scott, Sanjay Mehta, Michele Duggan, Aurelia Bihari, David G. McCormack
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Induction of inducible nitric oxide synthase (iNOS) expression is likely important in the pathogenesis of sepsis. However, the sepsis-mediated induction of iNOS is associated with a decrease in constitutive NO synthase (cNOS) activity (which is reversible following acute but not chronic sepsis). Whether this decreased cNOS activity is due to functional inhibition of cNOS by the high concentrations of NO produced by iNOS or to downregulation of cNOS expression is not clear. Thus, we tested the hypothesis that sepsis produces a reversible iNOS/NO-mediated inhibition of cNOS activity. Using a rat cecal ligation and perforation (CLP) model of sepsis, we examined the time course of the changes in iNOS and cNOS activities in lung and thoracic aortae. Reversibility of the sepsis-induced decrease in cNOS activity was assessed in vitro by enzyme activity determination following selective inhibition of iNOS. iNOS and endothelial cNOS protein concentrations were determined by Western blotting. In all septic tissues, cNOS activity was depressed at 6, 12, 24, and 48 hours post-CLP. Inhibition of the increased iNOS activity with aminoguanidine, in vitro, partially restored cNOS activity following acute (6–12 hours) but not chronic sepsis (24–48 hours post-CLP). Consistent with the irreversible depression of cNOS activities in tissues following chronic sepsis, endothelial NOS protein concentrations declined progressively during the time course of sepsis. We have demonstrated the restoration of cNOS activity following in vitro inhibition of iNOS, early, and the downregulation of endothelial NOS, later, in a rat CLP model of sepsis. This suggests that further study is required before iNOS-selective inhibition can be considered in human sepsis.
Performance of HbA1c as an Early Diagnostic Indicator of Type 1 Diabetes in Children and Youth
Authors: Kendra Vehik, David Cuthbertson, David Boulware, Craig A. Beam, Henry Rodriguez, Laurent Legault, Mila Hyytinen, Marian J. Rewers, Desmond A. Schatz, Jeffrey P. Krischer
Journal: Diabetes Care (2012)

The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age.
A Cytoplasmic NF-κB Interacting Long Noncoding RNA Blocks IκB Phosphorylation and Suppresses Breast Cancer Metastasis
Authors: Bodu Liu, Lijuan Sun, Qiang Liu, Chang Gong, Yandan Yao, Xiaobin Lv, Ling Lin, Herui Yao, Fengxi Su, Dangsheng Li, Musheng Zeng, Erwei Song
Journal: Cancer Cell (2015)
Insulin independence in a type 1 diabetic patient after encapsulated islet transplantation
Authors: P. Soon-Shiong, R.E. Heintz, N. Merideth, Q.X. Yao, Z. Yao, T. Zheng, M. Murphy, M.K. Moloney, M. Schmehl, M. Harris, R. Mendez, R. Mendez, P.A. Sandford
Journal: The Lancet (1994)
Safety of endobronchial biopsy in 170 children with chronic respiratory symptoms
Authors: P S Salva
Journal: Thorax (2003)

There is a paucity of bronchial biopsy data in children. A major limitation is concern over the safety of the procedure. This paper reports the results of efforts to develop a method that is safe and provides adequate specimen for evaluation.170 children aged 2.5 to 16 years with chronic respiratory symptoms were studied under general anaesthesia in an outpatient surgery setting. Bronchoalveolar lavage and biopsies were obtained using a 4.9 mm flexible bronchoscope through a laryngeal mask airway. At least three bioipsies were taken.No patient required topical adrenaline to control bleeding, nor was there a change in the state of any of the patients. There were no episodes of pneumothorax, haemoptysis, pneumonia, or significant fever. All children less than four years old received a single dose of antibiotic intravenously after the procedure. The average length of time for the procedure was 12 minutes (range 6 to 27). Recovery time averaged 90 minutes. The limiting factor was the ability of the child's airway to accomodate the bronchoscope.This report should encourage clinicians to incorporate endobronchial biopsy into the evaluation of children with difficult respiratory problems.
Prepublication of NIH Consensus Conferences on the Internet
Authors: John H. Ferguson
Journal: JAMA (1997)

<h3>To the Editor.</h3> —The National Institutes of Health (NIH) Consensus Development Program, begun in 1977 and managed by the NIH Office of Medical Applications of Research (OMAR), is a unique technology assessment process in American medicine and is designed to produce a consensus statement at the end of a 3-day consensus conference. An NIH Consensus Statement is a thoughtful and thorough data-driven synthesis of the current science based on a comprehensive review of the existing peer-reviewed medical literature, a series of state-of-the-art presentations, and public testimony. Thus, it has been our long-standing opinion that NIH Consensus Statements do not fall into the category of traditional scientific articles reporting original research that require peer review. Nonetheless, each NIH Consensus Statement is subjected to peer review by the experts in the field who review the document at the time of its public release. Nearly half of the 106 NIH Consensus Statements produced
Missed Opportunities and Lost Lives: Consequences of Some Proposed Changes to Regulations on Research with Human Tissues—Letter
Authors: William E. Grizzle
Journal: Clinical Cancer Research (2015)

Archival collections of paraffin blocks remaining after the diagnosis and treatment of diseases are frequently touted as a “treasure” in the study of human diseases. If so, why are the Department of Health and Human Services and other federal departments and agencies proposing to put this
Simultaneous occurrence of folliculitis decalvans capillitii in identical twins
Authors: K.E. Douwes, M. Landthaler, R-M. Szeimies
Journal: British Journal of Dermatology (2000)

Folliculitis decalvans is a chronic purulent folliculitis resulting in permanent hair loss and follicular atrophy. We report 32-year-old identical female twins presenting with relapsing pruritic outbreaks on the scalp resulting in areas of permanent baldness. Staphylococcus aureus was detected in the lesions of both women. Histopathology confirmed the diagnosis of folliculitis decalvans. Immunological testing showed no alteration of the immune system. To our knowledge, this is the first report on folliculitis decalvans occurring in identical twins, suggesting a possible genetic component in this disease.
Early influx of glomerular macrophages precedes glomerulosclerosis in the obese Zucker rat model.
Authors: S Lavaud, O Michel, C Sassy-Prigent, D Heudes, R Bazin, J Bariéty, J Chevalier
Journal: Journal of the American Society of Nephrology (1996)

Because hyperlipidemia and macrophage influx appear to play a key role in the genesis of renal glomerulosclerosis, this study examined the temporal relationship between hyperlipidemia (triglycerides and cholesterol), mononuclear cell influx, changes in glomerular structure, and expansion of the extracellular matrices in obese Zucker rats, which rapidly develop hyperlipidemia and spontaneous glomerulosclerosis. Lean and obese Zucker rats were fed a standard diet, and were euthanized at 14 days, 1, 3, 6, 9, and 12 months. Plasma lipid, insulin, and creatinine levels were measured, and the presence of inflammatory cells in the glomerulus was assessed by immunohistochemistry on kidney sections. Plasma lipids and insulin and macrophage density were significantly greater in obese than in lean rats as early as 1 month. Computer-assisted image analysis was used to evaluate the glomerular domain surface areas. The morphometric measurements showed that glomeruli of obese rats rapidly became hypertrophied after 3 months, as a result of a very large increase in the mesangial domain. The expression of genes for extracellular matrix components and inhibitors of extracellular matrix proteinases (TIMP-1 and TIMP-2) was monitored in microdissected glomeruli. Reverse transcription-polymerase chain reaction showed increases in mRNA for Type IV collagen and fibronectin and for the two metalloproteinase inhibitors, each of which might participate in this matrix expansion. Thus, the development of hyperlipidemia plus macrophage influx at a very early age may initiate a sequence of events leading to glomerulosclerosis later on.
EXPERIMENTAL GLOMERULONEPHRITIS
Authors: Frank J. Dixon, Joseph D. Feldman, Jacinto J. Vazquez
Journal: The Journal of Experimental Medicine (1961)

Daily injections of any one of several foreign serum proteins produced in rabbits functional and morphological alterations similar to those seen in acute, subacute, and chronic human glomerulonephritis. The critical factor determining whether a rabbit would develop renal disease and the type of disease developed was the amount of antibody the rabbit formed. Those responding with much antibody were likely to develop an acute, self-limited glomerulonephritis and to be subsequently immune to further renal damage. Those responding with antibody barely sufficient to neutralize the antigen injected developed subacute and chronic glomerulonephritis. In the circulation of the rabbits with chronic glomerulonephritis, there was a daily recurring antigen-antibody reaction in the region of near antigen excess to near antibody excess which presumably led to the disease. Antigen apparently in the form of antigen-antibody complexes was deposited along the renal capillary basement membranes coincident with the development of subacute and chronic glomerulonephritis. Once developed, the morphologic stigmata of chronic glomerulonephritis persisted even after injections of antigen were stopped. However, in milder instances the renal function recovered in part after stopping antigen. This experimental model has several implications: first, the renal injury is precipitated by antigens with no known affinity for, or immunologic relationship to, kidney; second, antigen antibody complexes localize in the kidney, apparently on the basis of non-immunologic factors, and may be an etiologic agent of renal injury; third, severe hypersensitivity disorders can be related specifically to relatively poor as well as to good antibody responses; and finally, the pathogenesis suggested here offers an alternative to that of nephrotoxic serum nephritis for the experimental approach to the study of human glomerulonephritis.
An ethics committee for the BMJ
Authors: A. McCall Smith
Journal: BMJ (2000)

Readers wondering why the BMJ or any other medical journal needs an ethics committee should read the latest annual report of the United Kingdom's Committee on Publication Ethics.1 It describes cases that until 1997—when the committee was set up—editors had to tackle alone: authors who cannot agree on their respective contributions to a piece of research, allegations of fraud (against editors as well as researchers), victimisation of whistleblowers, investigators who slice their work up in to “least publishable units” and submit to several different journals simultaneously, and research papers that come without ethics committee approval “because there isn't one in our hospital in [unnamed country].” Less dramatic issues come up every day: reviewers who write …
ARTERIAL BLOOD GASES AND ACID-BASE BALANCE IN NORMAL CHILDREN 1
Authors: Donald E. Cassels, Minerva Morse
Journal: Journal of Clinical Investigation (1953)

Robinson (1) studied the effect of age on the arterial blood gases and the acid-base balance of normal males from 5 to 91 years of age.In addition to the well known increase in oxygen com- bining capacity which occurs during childhood and adolescence, Robinson found moderately lower mean values for hemoglobin saturation in adults above 40 years of age, and slightly higher mean values for arterial CO2 content and CO2 tension in adults as compared with children.In the case of the alkaline reserve, mean values varied be- tween 21.2 and 22.2 millimols per liter for all age groups except the youngest.Robinson found un- usually low values of alkaline reserve in children 4 to 6 years of age.The present study was under- taken to supplement the work of Robinson in the years of childhood and adolescence, in order to establish more firmly the range of variation that may be expected in healthy children, and to pro- vide a basis for the study of arterial blood gases and acid base balance in disease. MATERIALThe subjects of the study were drawn from three
An essential role for macrophage migration inhibitory factor in the tuberculin delayed-type hypersensitivity reaction.
Authors: J Bernhagen, M Bacher, T Calandra, C N Metz, S B Doty, T Donnelly, R Bucala
Journal: The Journal of Experimental Medicine (1996)

30 years ago, investigations into the molecular basis of the delayed-type hypersensitivity reaction (DTH) provided evidence for the first lymphokine activity: a lymphocyte-derived mediator called macrophage migration inhibitory factor (MIF), which inhibited the random migration of peritoneal macrophages. Despite the long-standing association of MIF with the DTH reaction and the cloning of a human protein with macrophage migration inhibitory activity, the precise role of MIF in this classic cell-mediated immune response has remained undefined. This situation has been further complicated by the fact that two other cytokines, interferon gamma and IL-4, similarly inhibit macrophage migration and by the identification of mitogenic contaminants in some preparations of cloned human MIF. Using recently developed molecular probes for mouse MIF, we have examined the role of this protein in a classical model of DTH, the tuberculin reaction in mice. Both MIF messenger RNA and protein were expressed prominently in DTH lesions, as assessed by reverse transcription polymerase chain reaction, in situ hybridization, and immunostaining with anti-MIF antibody. The predominant cellular origin of MIF appeared to be the monocyte/macrophage, a cell type identified recently to be a major source of MIF release in vivo. The administration of neutralizing anti-MIF antibodies to mice inhibited significantly the development of DTH, thus affirming the central role of MIF in this classic immunological response.
Increasing smokers' risk perception improves CT screening participation
Authors: R P Young, R J Hopkins
Journal: Thorax (2012)

We read with interest the article by Patel et al 1 and wish to comment on their findings with specific regard to smokers' risk perception, motivation and low participation rates in CT screening programmes.

Based on the studies to date, there is a consistent theme that smokers' participation in CT screening programmes for lung cancer is poor when their motivation is low and much greater when their perception of risk of lung cancer is high.1 ,2 …
The Apoptotic Initiator Caspase-8: Its Functional Ubiquity and Genetic Diversity during Animal Evolution
Authors: Kazuhiro Sakamaki, Kouhei Shimizu, Hiroaki Iwata, Kenichiro Imai, Yutaka Satou, Noriko Funayama, Masami Nozaki, Mamiko Yajima, Osamu Nishimura, Mayura Higuchi, Kumiko Chiba, Michi Yoshimoto, Haruna Kimura, Andrew Y. Gracey, Takashi Shimizu, Kentaro Tomii, Osamu Gotoh, Koji Akasaka, Tatsuya Sawasaki, David J. Miller
Journal: Molecular Biology and Evolution (2014)

The caspases, a family of cysteine proteases, play multiple roles in apoptosis, inflammation, and cellular differentiation. Caspase-8 (Casp8), which was first identified in humans, functions as an initiator caspase in the apoptotic signaling mediated by cell-surface death receptors. To understand the evolution of function in the Casp8 protein family, casp8 orthologs were identified from a comprehensive range of vertebrates and invertebrates, including sponges and cnidarians, and characterized at both the gene and protein levels. Some introns have been conserved from cnidarians to mammals, but both losses and gains have also occurred; a new intron arose during teleost evolution, whereas in the ascidian Ciona intestinalis, the casp8 gene is intronless and is organized in an operon with a neighboring gene. Casp8 activities are near ubiquitous throughout the animal kingdom. Exogenous expression of a representative range of nonmammalian Casp8 proteins in cultured mammalian cells induced cell death, implying that these proteins possess proapoptotic activity. The cnidarian Casp8 proteins differ considerably from their bilaterian counterparts in terms of amino acid residues in the catalytic pocket, but display the same substrate specificity as human CASP8, highlighting the complexity of spatial structural interactions involved in enzymatic activity. Finally, it was confirmed that the interaction with an adaptor molecule, Fas-associated death domain protein, is also evolutionarily ancient. Thus, despite structural diversity and cooption to a variety of new functions, the ancient origins and near ubiquitous distribution of this activity across the animal kingdom emphasize the importance and utility of Casp8 as a central component of the metazoan molecular toolkit.
Microparticles: major transport vehicles for distinct microRNAs in circulation
Authors: P. Diehl, A. Fricke, L. Sander, J. Stamm, N. Bassler, N. Htun, M. Ziemann, T. Helbing, A. El-Osta, J. B. M. Jowett, K. Peter
Journal: Cardiovascular Research (2012)

AimsCirculating microRNAs (miRNAs) have attracted major interest as biomarkers for cardiovascular diseases. Since RNases are abundant in circulating blood, there needs to be a mechanism protecting miRNAs from degradation. We hypothesized that microparticles (MP) represent protective transport vehicles for miRNAs and that these are specifically packaged by their maternal cells.