tbuckley/cabot-search huggingface dataset:
Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation
Authors: Timothy J. Henrich, Emily Hanhauser, Francisco M. Marty, Michael N. Sirignano, Sheila Keating, Tzong-Hae Lee, Yvonne P. Robles, Benjamin T. Davis, Jonathan Z. Li, Andrea Heisey, Alison L. Hill, Michael P. Busch, Philippe Armand, Robert J. Soiffer, Marcus Altfeld, Daniel R. Kuritzkes
Journal: Annals of Internal Medicine (2014)

Background: It is unknown whether the reduction in HIV-1 reservoirs seen after allogeneic hematopoietic stem cell transplantation (HSCT) with susceptible donor cells is sufficient to achieve sustained HIV-1 remission. Objective: To characterize HIV-1 reservoirs in blood and tissues and perform analytic antiretroviral treatment interruptions to determine the potential for allogeneic HSCT to lead to sustained, antiretroviral-free HIV-1 remission. Design: Case report with characterization of HIV-1 reservoirs and immunity before and after antiretroviral interruption. Setting: Tertiary care center. Patients: Two men with HIV with undetectable HIV-1 after allogeneic HSCT for hematologic tumors. Measurements: Quantification of HIV-1 in various tissues after HSCT and the duration of antiretroviral-free HIV-1 remission after treatment interruption. Results: No HIV-1 was detected from peripheral blood or rectal mucosa before analytic treatment interruption. Plasma HIV-1 RNA and cell-associated HIV-1 DNA remained undetectable until 12 and 32 weeks after antiretroviral cessation. Both patients experienced rebound viremia within 2 weeks of the most recent negative viral load measurement and developed symptoms consistent with the acute retroviral syndrome. One patient developed new efavirenz resistance after reinitiation of antiretroviral therapy. Reinitiation of active therapy led to viral decay and resolution of symptoms in both patients. Limitation: The study involved only 2 patients. Conclusion: Allogeneic HSCT may lead to loss of detectable HIV-1 from blood and gut tissue and variable periods of antiretroviral-free HIV-1 remission, but viral rebound can occur despite a minimum 3-log10 reduction in reservoir size. Long-lived tissue reservoirs may have contributed to viral persistence. The definition of the nature and half-life of such reservoirs is essential to achieve durable antiretroviral-free HIV-1 remission. Primary Funding Source: Foundation for AIDS Research and National Institute of Allergy and Infectious Diseases.
Computers in Medicine: Notification of Death Occurring after Discharge from Hospital
Authors: M. R. Hubbard, E. D. Acheson
Journal: BMJ (1967)

Thus, in these ways clinical virology provides fields where routine and research work may profitably coexist hand in hand, much rewarding research stemming from properly collected specimens from well-documented cases. SummaryA diagnosis was made on 96 (36.6%) of 262 patients referred for virological investigations between 21 January 1966 and 20 January 1967.The highest numbers of patients were referred by the departments of paediatrics and venereology and from the physician in charge of nurses' health.The highest diagnostic rates were achieved on those patients referred by the nurses' physician (46.4%) and by the paediatricians (44.4%).Investi- gations on women exposed to or contracting rubella in early pregnancy, on infants with congenital malformations or neonatal infections, and on exanthematous infections which presented atypically were thought to be among the most useful studies conducted.Difficulties encountered in providing a fully com- prehensive diagnostic service are described, and emphasis is placed on the importance of conducting epidemiological, clinical, and virological studies on carefully selected material alongside routine diagnostic investigations.
Girls homozygous for an IL-2–inducible T cell kinase mutation that leads to protein deficiency develop fatal EBV-associated lymphoproliferation
Authors: Kirsten Huck, Oliver Feyen, Tim Niehues, Franz Rüschendorf, Norbert Hübner, Hans-Jürgen Laws, Tanja Telieps, Stefan Knapp, Hans-Heinrich Wacker, Alfons Meindl, Hassan Jumaa, Arndt Borkhardt
Journal: Journal of Clinical Investigation (2009)

The fatal immune dysregulation that sometimes follows EBV infection in boys has been linked to mutations in two X chromosome-encoded genes, SLAM-associated protein (SAP) and X-linked inhibitor of apoptosis (XIAP). In this study we describe 2 girls from a consanguineous Turkish family who died after developing severe immune dysregulation and therapy-resistant EBV-positive B cell proliferation following EBV infection. SNP array-based genome-wide linkage analysis revealed IL-2-inducible T cell kinase (ITK) as a candidate gene for this immunodeficiency syndrome. Both girls harbored a homozygous missense mutation that led to substitution of a highly conserved residue (R335W) in the SH2 domain of ITK. Characteristics of ITK deficiency in mouse models, such as absence of NKT cells and high levels of eomesodermin in CD8+ cells, were seen in either one or both of the girls. Two lines of evidence suggested that R335W caused instability of the ITK protein. First, in silico modeling of the mutant protein predicted destabilization of the SH2 domain. Additionally, Western blot analysis revealed that, unlike wild-type ITK, the R335W mutant was nearly undetectable when expressed in 293 T cells. Our results suggest that ITK deficiency causes what we believe to be a novel immunodeficiency syndrome that leads to a fatal inadequate immune response to EBV. Because ITK deficiency resembles EBV-associated lymphoproliferative disorders in boys, we suggest that this molecular cause should be considered during diagnosis and treatment.
Phase III Study of Interferon Alfa-NL as Adjuvant Treatment for Resectable Renal Cell Carcinoma: An Eastern Cooperative Oncology Group/Intergroup Trial
Authors: Edward M. Messing, Judith Manola, George Wilding, Kathleen Propert, Jonathan Fleischmann, E. David Crawford, J. Edson Pontes, Richard Hahn, Donald Trump
Journal: Journal of Clinical Oncology (2003)

To evaluate the role of adjuvant interferon alfa after complete resection of locally extensive renal cell carcinoma.A total of 283 eligible patients with pT3-4a and/or node-positive disease were randomly assigned after radical nephrectomy and lymphadenectomy to observation or to interferon alfa-NL (Wellferon, Burroughs-Wellcome, Research Park, NC) given daily for 5 days every 3 weeks for up to 12 cycles. Patients were stratified on the basis of pathologic stage. Patients remained on treatment until documented recurrence, excessive toxicity, or patient/physician preference deemed removal appropriate.At median follow-up of 10.4 years, median survival was 7.4 years in the observation arm and 5.1 year in the treatment arm (log-rank P =.09). Median recurrence-free survival was 3.0 years in the observation arm and 2.2 years in the interferon arm (P =.33). Performance status (P =.003), nodal status (N2 v N0, P <.0001), and tumor stage (P =.0002) were significant prognostic factors in multivariate analysis. A proportional hazards model examining the effects of treatment arm and time to recurrence on survival after recurrence among patients who recurred found that random assignment to interferon treatment (P =.009) and shorter time to recurrence (P <.0001) were independent predictors of shorter survival after recurrence. Although no lethal toxicities were observed, severe (grade 4) toxicities including neutropenia, myalgia, fatigue, depression, and other neurologic toxicities occurred in 11.4% of those randomly assigned to interferon treatment.Adjuvant treatment with interferon did not contribute to survival or relapse-free survival in this group of patients.
Supernormal Conduction in the Human Atria
Authors: ABDUL S. AGHA, CESAR A. CASTILLO, AGUSTIN CASTELLANOS, ROBERT J. MYERBURG, MICHAEL P. TESSLER
Journal: Circulation (1972)

A supernormal period of intra- and interatrial conduction was observed in five patients during premature stimulation of various atrial sites with driving cycle lengths ranging between 500 and 600 msec. Electrograms were recorded with filtered, 1-mm apart, bipolar catheter electrodes placed in the high right atrium, coronary sinus, and midleft atrium. The supernormal period, which lasted from 90 to 140 msec, was located at the end of the relative refractory period. During this part of the cycle, the response 1 -response 2 (R 1 -R 2 ) intervals were shorter than the corresponding St 1 -St 2 intervals. As in experiments performed with plunge electrodes, the conduction time of premature atrial responses was shorter than in late diastolic or driven beats. Although a mechanical origin (due to inevitable catheter movement produced with cardiac motion) can be invoked in the genesis of these changes, it is highly probable that supernormality was a true electrophysiologic event involving, predominantly, the specialized atrial tracts.
Functional Connectivity in Autosomal Dominant and Late-Onset Alzheimer Disease
Authors: Jewell B. Thomas, Matthew R. Brier, Randall J. Bateman, Abraham Z. Snyder, Tammie L. Benzinger, Chengjie Xiong, Marcus Raichle, David M. Holtzman, Reisa A. Sperling, Richard Mayeux, Bernardino Ghetti, John M. Ringman, Stephen Salloway, Eric McDade, Martin N. Rossor, Sebastien Ourselin, Peter R. Schofield, Colin L. Masters, Ralph N. Martins, Michael W. Weiner, Paul M. Thompson, Nick C. Fox, Robert A. Koeppe, Clifford R. Jack, Chester A. Mathis, Angela Oliver, Tyler M. Blazey, Krista Moulder, Virginia Buckles, Russ Hornbeck, Jasmeer Chhatwal, Aaron P. Schultz, Alison M. Goate, Anne M. Fagan, Nigel J. Cairns, Daniel S. Marcus, John C. Morris, Beau M. Ances
Journal: JAMA Neurology (2014)

Autosomal dominant Alzheimer disease (ADAD) is caused by rare genetic mutations in 3 specific genes in contrast to late-onset Alzheimer disease (LOAD), which has a more polygenetic risk profile. To assess the similarities and differences in functional connectivity changes owing to ADAD and LOAD. We analyzed functional connectivity in multiple brain resting state networks (RSNs) in a cross-sectional cohort of participants with ADAD (n = 79) and LOAD (n = 444), using resting-state functional connectivity magnetic resonance imaging at multiple international academic sites. For both types of AD, we quantified and compared functional connectivity changes in RSNs as a function of dementia severity measured by the Clinical Dementia Rating Scale. In ADAD, we qualitatively investigated functional connectivity changes with respect to estimated years from onset of symptoms within 5 RSNs. A decrease in functional connectivity with increasing Clinical Dementia Rating scores were similar for both LOAD and ADAD in multiple RSNs. Ordinal logistic regression models constructed in one type of Alzheimer disease accurately predicted clinical dementia rating scores in the other, further demonstrating the similarity of functional connectivity loss in each disease type. Among participants with ADAD, functional connectivity in multiple RSNs appeared qualitatively lower in asymptomatic mutation carriers near their anticipated age of symptom onset compared with asymptomatic mutation noncarriers. Resting-state functional connectivity magnetic resonance imaging changes with progressing AD severity are similar between ADAD and LOAD. Resting-state functional connectivity magnetic resonance imaging may be a useful end point for LOAD and ADAD therapy trials. Moreover, the disease process of ADAD may be an effective model for the LOAD disease process.
Mental distress and social conditions and lifestyle in northern Norway.
Authors: V. Hansen, B. K. Jacobsen
Journal: BMJ (1989)

In a cross sectional survey of risk factors for coronary heart disease three questions about mental distress were included in a questionnaire completed by 13,704 people, 64% of the total population aged 20-54 in one municipality. Overall, 860 (12.5%) of the men and 1141 (16.8%) of the women reported having at least one symptom of mental distress. There were no distinct differences between the age groups. Single people, separated and divorced people, and those who reported that the financial situation of the family during their childhood was difficult reported more mental problems. Heavy smoking, frequent alcohol consumption, and, in men, little or no physical activity in leisure time were also associated with a high prevalence of mental distress. By multiple regression analyses, marital state, financial situation of family during childhood, and current lifestyle were found to be highly significantly associated with mental distress. Including a few questions on mental distress in health surveys provides a way to establish relations between such symptoms and social conditions and lifestyle in large numbers of subjects.
Defective antifungal T-helper 1 (TH1) immunity in a murine model of allogeneic T-cell–depleted bone marrow transplantation and its restoration by treatment with TH2 cytokine antagonists
Authors: Antonella Mencacci, Katia Perruccio, Angela Bacci, Elio Cenci, Roberta Benedetti, Massimo F. Martelli, Francesco Bistoni, Robert Coffman, Andrea Velardi, Luigina Romani
Journal: Blood (2001)
Growth and differentiation of intestinal endodermal cells in a coculture system.
Authors: M Kedinger, P Simon-Assmann, K Haffen
Journal: Gut (1987)

To investigate the role of epithelial-mesenchymal interactions on intestinal maturation, we cultured embryonic epithelial cells in several experimental conditions. Microexplants of 14-15 days fetal rat intestinal endoderm, separated from the mesenchyme by collagenase, were seeded on dishes coated with different extracellular matrix components (collagens I, III, IV, fibronectin, laminin) or on confluent monolayers of intestinal mesenchymal cells or of fetal skin fibroblasts. Only small variations in the attachment or spreading of the endodermal cells could be observed when they were cultured on the different substrata and their survival never exceeded one week. When cocultured with intestinal or skin fibroblasts, however, endodermal cells grew, formed a monolayer, survival time was prolonged up to two to three weeks, and differentiation occurred. This differentiation was assessed by cell polarisation, morphological maturation of apical brush borders, synthesis of microvillar digestive enzymes and of extracellular matrix molecules seen immunocytochemically. Finally, glucocorticoids which are known to stimulate or induce brush border enzymes, accelerated the morphological and enzymatic maturation only in the cocultures.
The cyclin-dependent kinase inhibitor p57Kip2 mediates proliferative actions of PTHrP in chondrocytes
Authors: Helen E. MacLean, Jun Guo, Melissa C. Knight, Pumin Zhang, David Cobrinik, Henry M. Kronenberg
Journal: Journal of Clinical Investigation (2004)

Parathyroid hormone–related peptide (PTHrP) is a positive regulator of chondrocyte proliferation during bone development. In embryonic mice lacking PTHrP, chondrocytes stop proliferating prematurely, with accelerated differentiation. Because the bone phenotype of mice lacking the cyclin-dependent kinase inhibitor p57Kip2 is the opposite of the PTHrP-null phenotype, we hypothesized that PTHrP’s proliferative actions in chondrocytes might be mediated by opposing p57. We generated p57/PTHrP-null embryos, which showed partial rescue of the PTHrP-null phenotype. There was reversal of the loss of proliferative chondrocytes in most bones, with reversal of the accelerated differentiation that occurs in the PTHrP-null phenotype. p57 mRNA and protein were upregulated in proliferative chondrocytes in the absence of PTHrP. Metatarsal culture studies confirmed the action of PTHrP to decrease p57 mRNA and protein levels in a model in which parathyroid hormone (PTH), used as an analog of PTHrP, increased chondrocyte proliferation rate and the length of the proliferative domain. PTH treatment of p57-null metatarsals had no effect on proliferation rate in round proliferative chondrocytes but still stimulated proliferation in columnar chondrocytes. These studies suggest that the effects of PTHrP on both the rate and extent of chondrocyte proliferation are mediated, at least in part, through suppression of p57 expression.
Well informed uncertainties about the effects of treatment
Authors: Benjamin Djulbegovic
Journal: BMJ (2004)

Editor—As inevitable and unpleasant as many uncertainties are, one can argue that patients (and their doctors) should not even strive to completely eliminate uncertainties. Although the role of scientific method is to reduce uncertainties, a total elimination of uncertainty would be undesirable, since, it has been argued, it would lead to deterministic life—meaning that all events would be known in advance, in turn implying no hope, no ethics, no freedom of choice.1

Hence, there is a paradox in dealing with uncertainty—we want to reduce uncertainty, but we do not want to eliminate it totally.1 Only because we do not know what the future holds can we have our hope and choices.1 In the context of informing patients about the effects of treatments, this means that the patients' basic right is whether to accept that uncertainty2 exists (which in practice often means disagreement among their doctors), and the proposed method for resolution of the existing uncertainties (which can include enrolment into a clinical trial as one of the means to resolve uncertainties).3-5

Therefore, uncertainty should not be looked on as the enemy but rather as a friend (or as the opportunity). Once uncertainty is recognised and acknowledged,2-5 more effective solutions for its resolution can be devised. Hence, “two cheers for uncertainty.”1
Innate talent or deliberate practice as determinants of exceptional performance: Are we asking the right question?
Authors: Wolfgang Schneider
Journal: Behavioral and Brain Sciences (1998)

Howe et al. proposed that the “talent account” is not suited to explain exceptional performance in specific domains. Their conclusion that early experiences and deliberate practice are highly important for high levels of skill is supported by numerous studies on the acquisition of expertise. However, the two popular views they contrast (experts are born versus experts are made) do not seem representative of current theorizing. Models that integrate the effects of basic abilities and deliberate practice are more appropriate in light of the available evidence.
Influenza Vaccination with 1/10th the Full Dose
Authors: Curtis L. Cooper, Heather Davis, D.W. Cameron
Journal: New England Journal of Medicine (2004)

To the Editor: As a result of the recent problems in the production of influenza vaccine, there is concern about whether the demand for vaccine will outstrip the supply for the upcoming influenza season.1 An ample vaccine supply is an ever-present concern, given the potential for future influenza pandemics and avian influenza.2 We recently evaluated 1/10th-dose influenza vaccine (Fluarix) as part of a larger phase 1b, randomized, controlled, double-blind vaccine study.3 Healthy volunteers (age range, 18 to 40 years) with negative results on screening tests of hemagglutination inhibition (HAI) for A/Beijing/262/95 and B/Harbin/7/94 were enrolled after they had given written . . .
the next frontier: moral heuristics and the treatment of animals
Authors: harold a. herzog, gordon m. burghardt
Journal: Behavioral and Brain Sciences (2005)

heuristics provide insight into the inconsistencies that characterize thinking related to the use of nonhuman animals. we examine paradoxes in judgments and policy related to the treatment of animals in science from a moral intuition perspective. sunstein's ideas are consistent with a model of animal-related ethical evaluation we developed twenty-five years ago and which appear readily formulated as moral heuristics.
A human homologue of the Drosophila eyes absent gene underlies Branchio-Oto-Renal (BOR) syndrome and identifies a novel gene family
Authors: Sonia Abdelhak, Vasiliki Kalatzis, Roland Heilig, Sylvie Compain, Delphine Samson, Christophe Vincent, Dominique Weil, Corinne Cruaud, Iman Sahly, Michel Leibovici, Maria Bitner-Glindzicz, Mary Francis, Didier Lacombe, Jacqueline Vigneron, Robert Charachon, Katia Boven, Philippe Bedbeder, Nicole Van Regemorter, Jean Weissenbach, Christine Petit
Journal: Nature Genetics (1997)
Immunoglobulins cytophilic for human lymphocytes, monocytes, and neutrophils.
Authors: D A Lawrence, W O Weigle, H L Spiegelberg
Journal: Journal of Clinical Investigation (1975)

The cytophilic activity of human myeloma proteins of different classes and subclasses for lymphocytes, monocytes, and neutrophils was investigated. Binding of both unaggregated immunoglobulins (Ig) and Ig aggregated with rabbit F(ab)2 anti-Fab fragment sera was determined. Lymphocytes bound unaggregated IgG1 and IgG3 proteins, but none of the proteins of the other classes. In contrast, after aggregation, IgG of all subclasses and IgE proteins bound to lymphocytes; aggregated proteins of the other classes did not bind. Monocytes bound unaggregated IgG1 and Ig3 better than Ig4 whereas the binding of proteins of other classes was insignificant. Neutrophils bound unaggregated IgG1 and IgG3 proteins and, in addition, IgA1, IgA2, secretory IgA, and IgG4 proteins. After aggregation, the neutrophils bound more Ig of all classes; however, the differences between the amounts bound remained similar to the amounts of unaggregated proteins. The native structure of the Ig molecule is necessary for the maintenance of complete activity, because Fc fragments bound less than intact Ig, and reduction and alkylation abolished cytophilia. The Fc receptors on all cell types tested showed no specificity for any of the respective cytophilic IgG subclasses; however, neutrophils appear to have separate receptors for IgG and IgA proteins.
Infectious diseases of the upper respiratory tract: implications for toxicology studies.
Authors: J I Everitt, C B Richter
Journal: Environmental Health Perspectives (1990)

The consequences of adventitious infectious agents upon the interpretation of toxicology studies performed in rats and mice are incompletely understood. Several prevalent murine pathogens cause alterations of the respiratory system that can confuse the assessment of chemically induced airway injury. In some instances the pathogenesis of infection with these agents has been relatively well studied in the lower respiratory tract. However, there are few well-controlled studies that have examined the upper respiratory region, which result in interpretive problems for toxicologic pathologists. The conduct and interpretation of both short-term and chronic rodent bioassays can be compromised by both the clinical and subclinical manifestations of infectious diseases. This paper reviews several important infectious diseases of the upper airway of rats and mice and discusses the potential influence of these conditions on the results of toxicology studies.
385 SIGNIFICANCE OF TRANSIENT ELASTOGRAPHY (TE) IN HBEAG-NEGATTVE CHRONIC HBV CARRIERS
Authors: G.V. Papatheodoridis, E. Margariti, M.-V. Papageorgiou, H. Kranidioti, A. Katoglou, A. Striki, G. Kaflri, S. Manolakopoulos
Journal: Journal of Hepatology (2011)
Association of HLA-DRB1–restricted CD4+ T cell responses with HIV immune control
Authors: Srinika Ranasinghe, Sam Cutler, Isaiah Davis, Richard Lu, Damien Z Soghoian, Ying Qi, John Sidney, Gregory Kranias, Michael D Flanders, Madelene Lindqvist, Bjorn Kuhl, Galit Alter, Steven G Deeks, Bruce D Walker, Xiaojiang Gao, Alessandro Sette, Mary Carrington, Hendrik Streeck
Journal: Nature Medicine (2013)