tbuckley/cabot-search huggingface dataset:
Impaired tuftsin activity in cirrhosis: relationship with splenic function and clinical outcome
Authors: F Trevisani
Journal: Gut (2002)

Cirrhotic patients show increased susceptibility to bacterial infections. It is not known whether tuftsin deficiency, which is associated with an increased incidence of infections in many disease states, is present in cirrhosis. Our aims were to determine whether tuftsin activity is deficient in cirrhosis and if so, whether this deficiency is related to splenic function, contributes to altered neutrophil granulocyte function, or influences the occurrence of bacterial infections and patient survival.Tuftsin activity and splenic function were assessed in 31 patients with liver cirrhosis and 31 healthy subjects. The phagocytic activity of neutrophil granulocytes from 23 patients was tested in vitro with addition of both autologous and pooled sera from healthy subjects. In 10 patients and eight controls it was also tested with addition of synthetic tuftsin. Patients were followed up until death or liver transplantation.Patients had reduced tuftsin activity (median 8% (range 3-24.5)) compared with controls (17% (11.5-37)) (p<0.001) and a higher pitted red cell count (p<0.001). Tuftsin activity was correlated with pitted cell count (p=0.02) and the Child-Pugh score (p=0.002). Nineteen of 23 patients showed deficient phagocytic activity of neutrophil granulocytes, which was correlated with tuftsin activity (p<0.001), improved in all cases but one with addition of serum from healthy subjects, and normalised with addition of synthetic tuftsin. Reduced tuftsin activity did not influence patient survival but was associated with a higher incidence of bacterial infections (p=0.029).Tuftsin activity was reduced in cirrhosis, and contributed to impaired phagocytic activity of neutrophil granulocytes. Such an abnormality appears to be related to impaired splenic function and severity of cirrhosis, and probably favours the occurrence of bacterial infections.
A Generalized Linear-Quadratic Model for Radiosurgery, Stereotactic Body Radiation Therapy, and High–Dose Rate Brachytherapy
Authors: Jian Z. Wang, Zhibin Huang, Simon S. Lo, William T. C. Yuh, Nina A. Mayr
Journal: Science Translational Medicine (2010)

A generalized mathematical model for the relation between radiation dose and tumor cell death enables better treatment planning and dose schedule designs for current targeted high-dose radiation therapies in cancer.
Poor prognosis for P2RY8-CRLF2 fusion but not for CRLF2 over-expression in children with intermediate risk B-cell precursor acute lymphoblastic leukemia
Authors: C Palmi, E Vendramini, D Silvestri, G Longinotti, D Frison, G Cario, C Shochat, M Stanulla, V Rossi, A M Di Meglio, T Villa, E Giarin, G Fazio, A Leszl, M Schrappe, G Basso, A Biondi, S Izraeli, V Conter, M G Valsecchi, G Cazzaniga, G te Kronnie
Journal: Leukemia (2012)
S119 Roles of TLR3, TLR4- and TLRs7–9 in Interferon Induction in Bronchial Epithelial Cells and Peripheral Blood Mononuclear Cells from Asthmatic and Non-Asthmatic Subjects
Authors: A Sykes, MR Edwards, J Macintyre, A del Rosario, OM Kon, SL Johnston
Journal: Thorax (2012)

<h3>Introduction</h3> Defective rhinovirus (RV) induced interferon (IFN)-β and IFN-λ production has been reported in primary human bronchial epithelial cells (HBECs) and peripheral blood mononuclear cells (PBMCs) from asthmatics. The mechanisms of defective IFN induction in asthma are unknown. Virus infection can induce IFNs through Toll like Receptors (TLR)3, TLR4 and TLRs7–9 and TLR agonists have been identified as potential therapeutic options for asthma. The role of these TLRs in IFN induction in asthma is unclear. <h3>Objective</h3> To investigate IFN responses to TLR stimulation in HBECs and PBMCs from atopic asthmatic and non-asthmatic individuals. <h3>Methods</h3> HBECs and PBMCs from atopic asthmatic and non-asthmatic subjects were stimulated with agonists to TLR3, TLR4 &amp; TLRs7–9 and type I and III IFN responses assessed by qPCR and ELISA. <h3>Results</h3> TLR3 and TLR7, but not TLR4, 8 or 9, stimulation induced IFN protein and mRNA expression in HBECs and PBMCs. IFNs induced were IFN-β and predominantly type III IFN-λ in HBECs and type I (–α and –β) with no IFN-λ in PBMCs. TLR function was not defective in asthmatic compared to non-asthmatic subjects. <h3>Conclusions</h3> TLR3 &amp; TLR7 were the predominant TLRs involved in IFN induction in HBECs and PBMCs. Defective IFN induction to TLR agonists was not observed in these well controlled asthmatic subjects. TLR3/7 agonists could be effective in inducing IFNs in more severe/less well controlled asthmatics who may have deficient virus induced IFN production.
Induction of idiotype-specific suppressor T cells with antigen/antibody complexes.
Authors: M J Caulfield, K J Luce, M R Proffitt, J Cerny
Journal: The Journal of Experimental Medicine (1983)

The effects of immune complexes on the antibody response of BALB/c mice to Streptococcus pneumoniae R36a (Pn) were investigated. The cell wall polysaccharide (PnC) extracted from Pn was used to form complexes with TEPC-15, a myeloma protein that binds to phosphorylcholine determinants on the PnC. Complexes formed at equivalence were cultured with splenic T cells from BALB/c mice for 2 d, and then the cells were added to fresh BALB/c spleen cell cultures to test their effect on the antibody response to Pn, a response dominated by the T15 idiotype family. The results indicate that TEPC-15/PnC complexes induced potent suppressor T cells (Ts) whereas cells cultured with free antigen or free antibody alone had no effect on the plaque-forming cell response to Pn. The suppression was specific since the response to control antigens such as sheep erythrocytes was unaffected. The suppression appears to be idiotype-specific since the Ts had a relatively weak (and in some cases no) effect on the anti-Pn response of BALB/c mice that had been suppressed for T15 idiotopes by neonatal injection of a monoclonal anti-T15 antibody, MaId 5-4. Furthermore, cells cultured with TEPC-15/PnC complexes were shown to express specific receptors for TEPC-15 idiotopes. The results indicate that antigen/antibody complexes may have important immunoregulatory effects because they are potent inducers of idiotype-specific Ts.
Factors Contributing to Therapists’ Distress After the Suicide of a Patient
Authors: Herbert Hendin, Ann Pollinger Haas, John T Maltsberger, Katalin Szanto, Heather Rabinowicz
Journal: American Journal of Psychiatry (2004)

Factors contributing to therapists' severe distress after the suicide of a patient were investigated.Therapists for 34 patients who died by suicide completed a semistructured questionnaire about their reactions, wrote case narratives, and participated in a workshop.Thirteen of the 34 therapists were severely distressed. Four factors were identified as sources of severe distress: failure to hospitalize an imminently suicidal patient who then died, a treatment decision the therapist felt contributed to the suicide, negative reactions from the therapist's institution, and fear of a lawsuit by the patient's relatives. Although one emotion was sometimes dominant in the therapist's response to the suicide, severely distressed therapists, compared to others, reported a significantly larger number of intense emotional states.Over one-third of therapists who experienced a patient's suicide were found to suffer severe distress, pointing to the need for further study of the long-term effects of patient suicide on professional practice.
Variation in DNA content of immature normal bone marrow cells
Authors: S. Widell, G. Auer, R. Hast, P. Reizenstein
Journal: American Journal of Hematology (1993)

A variability in DNA content detected was found with image cytometry, in immature bone marrow cells from 13 healthy donors (median age 31 yr). The mean coefficient of variation (C.V.) of the DNA content was found to be significantly (P = 0.0002) higher in immature blasts and promyelocytes than in mature granulocytes, lymphocytes, and monocytes. The finding was not due to high DNA contents secondary to DNA-synthesis in immature cells, since the percentage of such cells with a reduced DNA content was also significantly (P = 0.0424-0.0002) increased. The error of the method expressed as the variance of multiple measurements has been found to be 0.0002-0.0004. A staining error has been found for some hydrolysis times, but not for times between 60 and 120 minutes. A measuring error was found for an average of 1.38 to 3.38% of the cells. If many normal cells with DNA-aneuploidy are sterile, this would explain the present findings as well as previous ones about intra-marrow cell death, and also the fact that the variability in DNA content could not be detected with cytogenetic or flow cytometric methods.
Intermittent HIV-1 Viremia (Blips) and Drug Resistance in Patients Receiving HAART
Authors: Richard E. Nettles
Journal: JAMA (2005)

2][3] The current goal of antiretroviral therapy is suppression of viremia to below 50 copies/mL of HIV-1 RNA, the limit of detection of the most sensitive available clinical assay. 4,5Suppression to this level is necessary to prevent drug resistance, the major cause of treatment failure. 6,7][10][11][12][13][14][15][16] Blips may raise concern that resistance is developing and complicate management by increasing patient anxiety, triggering costly repeat measurements of viral load, and generating uncertainty re-
Atazanavir Plus Ritonavir or Efavirenz as Part of a 3-Drug Regimen for Initial Treatment of HIV-1
Authors: Eric S. Daar
Journal: Annals of Internal Medicine (2011)

Limited data compare once-daily options for initial therapy for HIV-1.To compare time to virologic failure; first grade-3 or -4 sign, symptom, or laboratory abnormality (safety); and change or discontinuation of regimen (tolerability) for atazanavir plus ritonavir with efavirenz-containing initial therapy for HIV-1.A randomized equivalence trial accrued from September 2005 to November 2007, with median follow-up of 138 weeks. Regimens were assigned by using a central computer, stratified by screening HIV-1 RNA level less than 100 000 copies/mL or 100 000 copies/mL or greater; blinding was known only to the site pharmacist. (ClinicalTrials.gov registration number: NCT00118898)59 AIDS Clinical Trials Group sites in the United States and Puerto Rico.Antiretroviral-naive patients.Open-label atazanavir plus ritonavir or efavirenz, each given with with placebo-controlled abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine.Primary outcomes were time to virologic failure, safety, and tolerability events. Secondary end points included proportion of patients with HIV-1 RNA level less than 50 copies/mL, emergence of drug resistance, changes in CD4 cell counts, calculated creatinine clearance, and lipid levels.463 eligible patients were randomly assigned to receive atazanavir plus ritonavir and 465 were assigned to receive efavirenz, both with abacavir-lamivudine; 322 (70%) and 324 (70%), respectively, completed follow-up. The respective numbers of participants in each group who received tenofovir DF-emtricitabine were 465 and 464; 342 (74%) and 343 (74%) completed follow-up. Primary efficacy was similar in the group that received atazanavir plus ritonavir and and the group that received efavirenz and did not differ according to whether abacavir-lamivudine or tenofovir DF-emtricitabine was also given. Hazard ratios for time to virologic failure were 1.13 (95% CI, 0.82 to 1.56) and 1.01 (CI, 0.70 to 1.46), respectively, although CIs did not meet prespecified criteria for equivalence. The time to safety (P = 0.048) and tolerability (P < 0.001) events was longer in persons given atazanavir plus ritonavir than in those given efavirenz with abacavir-lamivudine but not with tenofovir DF-emtricitabine.Neither HLA-B*5701 nor resistance testing was the standard of care when A5202 enrolled patients. The third drugs, atazanavir plus ritonavir and efavirenz, were open-label; the nucleoside reverse transcriptase inhibitors were prematurely unblinded in the high viral load stratum; and 32% of patients modified or discontinued treatment with their third drug.Atazanavir plus ritonavir and efavirenz have similar antiviral activity when used with abacavir-lamivudine or tenofovir DF-emtricitabine.National Institutes of Health.
Therapeutic Options for the Treatment of Impaired Gut Function
Authors: A Meier-Hellmann, K Reinhart, D L Bredle, S G Sakka
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Tissue hypoxia, especially in the splanchnic area, is still considered to be an important cofactor in the pathogenesis of multiple organ failure. Therefore, the specific effects of the various therapeutic interventions on splanchnic perfusion and oxygenation are of particular interest. Restoring and maintaining oxygen transport and tissue oxygenation is the most important step in the supportive treatment of patients with sepsis and impaired gut perfusion. Therefore, supportive treatment should be focused on an adequate volume resuscitation and appropriate use of vasoactive drugs. Adequate volume loading may be the most important step in the treatment of patients with septic shock. An elevated oxygen delivery may be beneficial in some patients, but the increase of oxygen delivery should be guided by the measurement of parameters assessing global and regional oxygenation. Forcing an elevation in oxygen delivery by the use of very high dosages of catecholamines can be harmful. Vasopressors should be used for achieving an adequate perfusion pressure. For norepinephrine, no negative effects on gut perfusion have been demonstrated. Epinephrine and dopamine should be avoided because they seem to redistribute blood flow away from the splanchnic region. There are no convincing data yet to support the routine use of low-dose dopamine or dopexamine to improve an impaired gut perfusion. There is even evidence that low-dose dopamine may reduce the mucosal perfusion in the gut in some patients. It has been suggested that dopexamine can improve splanchnic perfusion, but because these effects remain somewhat controversial, a general recommendation for dopexamine to improve gut perfusion is not justified.
CORTICAL PLASTICITY: From Synapses to Maps
Authors: Dean V. Buonomano, Michael M. Merzenich
Journal: Annual Review of Neuroscience (1998)

▪ Abstract It has been clear for almost two decades that cortical representations in adult animals are not fixed entities, but rather, are dynamic and are continuously modified by experience. The cortex can preferentially allocate area to represent the particular peripheral input sources that are proportionally most used. Alterations in cortical representations appear to underlie learning tasks dependent on the use of the behaviorally important peripheral inputs that they represent. The rules governing this cortical representational plasticity following manipulations of inputs, including learning, are increasingly well understood. In parallel with developments in the field of cortical map plasticity, studies of synaptic plasticity have characterized specific elementary forms of plasticity, including associative long-term potentiation and long-term depression of excitatory postsynaptic potentials. Investigators have made many important strides toward understanding the molecular underpinnings of these fundamental plasticity processes and toward defining the learning rules that govern their induction. The fields of cortical synaptic plasticity and cortical map plasticity have been implicitly linked by the hypothesis that synaptic plasticity underlies cortical map reorganization. Recent experimental and theoretical work has provided increasingly stronger support for this hypothesis. The goal of the current paper is to review the fields of both synaptic and cortical map plasticity with an emphasis on the work that attempts to unite both fields. A second objective is to highlight the gaps in our understanding of synaptic and cellular mechanisms underlying cortical representational plasticity.
A Diverse Population of Introns in the Nuclear Ribosomal Genes of Ericoid Mycorrhizal Fungi Includes Elements with Sequence Similarity to Endonuclease-Coding Genes
Authors: S Perotto, P Nepote-Fus, L Saletta, C Bandi, J P Young
Journal: Molecular Biology and Evolution (2000)

Ericoid mycorrhizal fungi form symbioses with the roots of members of the Ericales. Although only two genera have been identified in culture, the taxonomic diversity of ericoid symbionts is certainly wider. Genetic variation among 40 ericoid fungal isolates was investigated in this study. PCR amplification of the nuclear small-subunit ribosomal DNA (SSU rDNA) and of the internal transcribed spacer (ITS), followed by sequencing, led to the discovery of DNA insertions of various sizes in the SSU rDNA of most isolates. They reached sizes of almost 1,800 bp and occurred in up to five different insertion sites. Their positions and sizes were generally correlated with morphological and ITS-RFLP grouping of the isolates, although some insertions were found to be optional among isolates of the same species, and insertions were not always present in all SSU rDNA repeats within an isolate. Most insertions were identified as typical group I introns, possessing the conserved motifs characteristic of this group. However, other insertions lack these motifs and form a distinct group that includes other fungal ribosomal introns. Alignments with almost 70 additional sequences from fungal nuclear SSU rDNA introns indicate that introns inserted at the same site along the rDNA gene are generally homologous, but they also suggest the possibility of some horizontal transfers. Two of the ericoid fungal introns showed strong homology with a conserved motif found in endonuclease genes from nuclear rDNA introns.
Arginase 2 deficiency results in spontaneous steatohepatitis: A novel link between innate immune activation and hepatic de novo lipogenesis
Authors: Laura A. Navarro, Alexander Wree, Davide Povero, Michael P. Berk, Akiko Eguchi, Sudakshina Ghosh, Bettina G. Papouchado, Serpil C. Erzurum, Ariel E. Feldstein
Journal: Journal of Hepatology (2014)
Trajectories of Disability in the Last Year of Life
Authors: Thomas M. Gill, Evelyne A. Gahbauer, Ling Han, Heather G. Allore
Journal: New England Journal of Medicine (2010)

Despite the importance of functional status to older persons and their families, little is known about the course of disability at the end of life.We evaluated data on 383 decedents from a longitudinal study involving 754 community-dwelling older persons. None of the subjects had disability in essential activities of daily living at the beginning of the study, and the level of disability was ascertained during monthly interviews for more than 10 years. Information on the conditions leading to death was obtained from death certificates and comprehensive assessments that were completed at 18-month intervals after the baseline assessment.In the last year of life, five distinct trajectories were identified, from no disability to the most severe disability: 65 subjects had no disability (17.0%), 76 had catastrophic disability (19.8%), 67 had accelerated disability (17.5%), 91 had progressive disability (23.8%), and 84 had persistently severe disability (21.9%). The most common condition leading to death was frailty (in 107 subjects [27.9%]), followed by organ failure (in 82 subjects [21.4%]), cancer (in 74 subjects [19.3%]), other causes (in 57 subjects [14.9%]), advanced dementia (in 53 subjects [13.8%]), and sudden death (in 10 subjects [2.6%]). When the distribution of the disability trajectories was evaluated according to the conditions leading to death, a predominant trajectory was observed only for subjects who died from advanced dementia (67.9% of these subjects had a trajectory of persistently severe disability) and sudden death (50.0% of these subjects had no disability). For the four other conditions leading to death, no more than 34% of the subjects had any of the disability trajectories. The distribution of disability trajectories was particularly heterogeneous among the subjects with organ failure (from 12.2 to 32.9% of the subjects followed a specific trajectory) and frailty (from 14.0 to 27.1% of the subjects followed a specific trajectory).In most of the decedents, the course of disability in the last year of life did not follow a predictable pattern based on the condition leading to death.
The protein tyrosine phosphatase PTP1B is a negative regulator of CD40 and BAFF-R signaling and controls B cell autoimmunity
Authors: David Medgyesi, Elias Hobeika, Robert Biesen, Florian Kollert, Adriano Taddeo, Reinhard E. Voll, Falk Hiepe, Michael Reth
Journal: The Journal of Experimental Medicine (2014)

Tyrosine phosphorylation of signaling molecules that mediate B cell activation in response to various stimuli is tightly regulated by protein tyrosine phosphatases (PTPs). PTP1B is a ubiquitously expressed tyrosine phosphatase with well-characterized functions in metabolic signaling pathways. We show here that PTP1B negatively regulates CD40, B cell activating factor receptor (BAFF-R), and TLR4 signaling in B cells. Specifically, PTP1B counteracts p38 mitogen-activated protein kinase (MAPK) activation by directly dephosphorylating Tyr182 of this kinase. Mice with a B cell–specific PTP1B deficiency show increased T cell–dependent immune responses and elevated total serum IgG. Furthermore, aged animals develop systemic autoimmunity with elevated serum anti-dsDNA, spontaneous germinal centers in the spleen, and deposition of IgG immune complexes and C3 in the kidney. In a clinical setting, we observed that B cells of rheumatoid arthritis patients have significantly reduced PTP1B expression. Our data suggest that PTP1B plays an important role in the control of B cell activation and the maintenance of immunological tolerance.
Relative rates of non-pneumonic SARS coronavirus infection and SARS coronavirus pneumonia
Authors: Patrick CY Woo, Susanna KP Lau, Hoi-wah Tsoi, Kwok-hung Chan, Beatrice HL Wong, Xiao-yan Che, Victoria KP Tam, Sidney CF Tam, Vincent CC Cheng, Ivan FN Hung, Samson SY Wong, Bo-jian Zheng, Yi Guan, Kwok-yung Yuen
Journal: The Lancet (2004)
The nucleotide binding motif of hepatitis C virus NS4B can mediate cellular transformation and tumor formation without Ha-ras co-transfection
Authors: Shirit Einav, Ella H. Sklan, Hyang Mi Moon, Elizabeth Gehrig, Ping Liu, Ying Hao, Anson W. Lowe, Jeffrey S. Glenn
Journal: Hepatology (2007)

Hepatitis C virus (HCV) is an important cause of chronic liver disease and is complicated by hepatocellular carcinoma (HCC). Mechanisms whereby the virus promotes cellular transformation are poorly understood. We hypothesized that the guanosine triphosphatase activity encoded in the HCV NS4B protein's nucleotide binding motif (NBM) might play a role in the transformation process. Here we report that NS4B can transform NIH-3T3 cells, leading to tumor formation in vivo . This transformation was independent of co-transfection with activated Ha-ras. Detailed analyses of NS4B mutants revealed that this transforming activity could be progressively inhibited and completely abrogated by increasing genetic impairment of the NS4B nucleotide binding motif. Conclusion: NS4B has in vitro and in vivo tumorigenic potential, and the NS4B transforming activity is indeed mediated by its NBM. Moreover, our results suggest that pharmacological inhibition of the latter might inhibit not only HCV replication but also the associated HCC.