tbuckley/cabot-search huggingface dataset:
Comparative Effect of Atypical and Conventional Antipsychotic Drugs on Neurocognition in First-Episode Psychosis: A Randomized, Double-Blind Trial of Olanzapine Versus Low Doses of Haloperidol
Authors: Richard S.E. Keefe, Larry J. Seidman, Bruce K. Christensen, Robert M. Hamer, Tonmoy Sharma, Margriet M. Sitskoorn, Richard R.J. Lewine, Deborah A. Yurgelun-Todd, Ruben C. Gur, Mauricio Tohen, Gary D. Tollefson, Todd M. Sanger, Jeffrey A. Lieberman
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: The effect of antipsychotic medication on neurocognitive function remains controversial, especially since most previous work has compared the effects of novel antipsychotic medications with those of high doses of conventional medications. This study compares the neurocognitive effects of olanzapine and low doses of haloperidol in patients with first-episode psychosis. METHOD: Patients with a first episode of schizophrenia, schizoaffective disorder, or schizophreniform disorder (N=167) were randomly assigned to double-blind treatment with olanzapine (mean modal dose= 9.63 mg/day) or haloperidol (mean modal dose=4.60 mg/day) for the 12-week acute phase of a 2-year study. The patients were assessed with a battery of neurocognitive tests at baseline and 12 weeks after beginning treatment. RESULTS: An unweighted neurocognitive composite score, composed of measures of verbal fluency, motor functions, working memory, verbal memory, and vigilance, improved significantly with both haloperidol and olanzapine treatment (effect sizes of 0.20 and 0.36, respectively, no significant difference between groups). A weighted composite score developed from a principal-component analysis of the same measures improved to a significantly greater degree with olanzapine, compared with haloperidol. Anticholinergic use, extrapyramidal symptoms, and estimated IQ had little effect on the statistical differentiation of the medications, although duration of illness had a modest effect. The correlations of cognitive improvement with changes in clinical characteristics and with side effects of treatment were significant for patients who received haloperidol but not for patients who received olanzapine. CONCLUSIONS: Olanzapine has a beneficial effect on neurocognitive function in patients with a first episode of psychosis. However, in a comparison of the effects of olanzapine and low doses of haloperidol, the difference in benefit is small.
A Unique Subset of CD4+CD25highFoxp3+ T Cells Secreting Interleukin-10 and Transforming Growth Factor-β1 Mediates Suppression in the Tumor Microenvironment
Authors: Laura Strauss, Christoph Bergmann, Miroslaw Szczepanski, William Gooding, Jonas T. Johnson, Theresa L. Whiteside
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Immunosuppression, including that mediated by CD4+CD25highFoxp3+ regulatory T cells (Treg), is a characteristic feature of head and neck squamous cell carcinoma (HNSCC). Tregs with a distinct phenotype in tumor-infiltrating lymphocytes (TIL) contribute to local immune suppression. Experimental Design: The frequency and phenotype of Treg in TIL and/or peripheral blood mononuclear cells (PBMC) in 15 HNSCC patients and PBMC in 15 normal controls were compared. Single-cell sorted CD4+CD25high T cells were tested for regulatory function by coculture with carboxyfluorescein diacetate succinimidyl ester–labeled and activated autologous CD4+CD25− responder T cells. Transwell inserts separating Treg from responders and neutralizing interleukin-10 (IL-10) or transforming growth factor-β1 (TGF-β1) antibodies were used to evaluate the mechanisms used by Treg to suppress responder cell proliferation. Results: In TIL, CD25+ cells were enriched in the CD3+CD4+ subset (13 ± 3%) relative to circulating CD3+CD4+ T cells (3 ± 0.7%) in HNSCC patients (P ≤ 0.01) or normal controls (2 ± 1.5%; P ≤ 0.001). Among the CD3+CD4+ subset, CD25high Treg represented 3 ± 0.5% in TIL, 1 ± 0.3% in PBMC, and 0.4 ± 0.2% in normal controls. Tregs in TIL were GITR+, IL-10+, and TGF-β1+, although circulating Treg up-regulated CD62L and CCR7 but not GITR, IL-10, or TGF-β1. Treg in TIL mediated stronger suppression (P ≤ 0.001) than Treg in PBMC of HNSCC patients. The addition of neutralizing IL-10 and TGF-β antibodies almost completely abrogated suppression (5 ± 2.51%). Transwell inserts partly prevented suppression (60 ± 5% versus 95 ± 5%). Conclusions: Suppression in the tumor microenvironment is mediated by a unique subset of Treg, which produce IL-10 and TGF-β1 and do not require cell-to-cell contact between Treg and responder cells for inhibition.
Eosinophil involvement and serum IgE level in HIV-1–infected children☆☆☆★
Authors: José Onorato, Susanna Esposito, Elena Scovena, Beatrice Morandi, Marco Morelli, Monica Pizzi, Giuliana Zisa, Paola Marchisio, Nicola Principi
Journal: Journal of Allergy and Clinical Immunology (1999)
CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group
Authors: Michael Pfreundschuh, Evelyn Kuhnt, Lorenz Trümper, Anders Österborg, Marek Trneny, Lois Shepherd, Devinder S Gill, Jan Walewski, Ruth Pettengell, Ulrich Jaeger, Pier-Luigi Zinzani, Ofer Shpilberg, Stein Kvaloy, Peter de Nully Brown, Rolf Stahel, Noel Milpied, Armando López-Guillermo, Viola Poeschel, Sandra Grass, Markus Loeffler, Niels Murawski
Journal: The Lancet Oncology (2011)
Characterization of woodchuck hepatitis virus DNA and RNA in the hepatocellular carcinomas of woodchucks
Authors: Klaus Fuchs, Claudia Heberger, Thomas Weimer, Michael Roggendorf
Journal: Hepatology (1989)

Integration and transcription of woodchuck hepatitis virus DNA were studied by Southern and Northern blot analysis in 26 hepatocellular carcinomas and in adjacent nontumor tissue of woodchucks (Marmota monax). All liver tissue chronically infected with woodchuck hepatitis virus contained various amounts of episomal and replicative forms of woodchuck hepatitis virus DNA: episomal and replicative forms of woodchuck hepatitis virus DNA without integration were found in six tumors, episomal and integrated woodchuck hepatitis virus DNA was observed in 18 tumors and exclusively integrated woodchuck hepatitis virus DNA was found in two tumors. In most tumors and in all of the liver tissues chronically infected with woodchuck hepatitis virus, two major woodchuck hepatitis virus RNA species (3.7 and 2.1 kilobases) were detected. In tumors of two other animals (HW76 and HW89) with integrated woodchuck hepatitis virus DNA, only single major transcripts of 3.5 and 2.5 kilobases, respectively, were detected. Hybridization with subcloned woodchuck hepatitis virus DNA probes showed that both aberrant transcripts lacked the C gene and a part of the pre-S1 gene; characterization of corresponding integrated woodchuck hepatitis virus DNA sequences revealed that the C gene was deleted in one tumor, although not in the other. In agreement with the nucleic acid data, we found expression of core protein by Western blotting only in chronically infected liver tissue of these animals, but not in the corresponding tumors. Deletion of the C gene in mRNA may be due to deletion of this gene in the integrated sequences or due to transcriptional regulation.
B-Raf Activation Cooperates with PTEN Loss to Drive c-Myc Expression in Advanced Prostate Cancer
Authors: Jingqiang Wang, Takashi Kobayashi, Nicolas Floc'h, Carolyn Waugh Kinkade, Alvaro Aytes, David Dankort, Celine Lefebvre, Antonina Mitrofanova, Robert D. Cardiff, Martin McMahon, Andrea Califano, Michael M. Shen, Cory Abate-Shen
Journal: Cancer Research (2012)

Both the PI3K → Akt → mTOR and mitogen-activated protein kinase (MAPK) signaling pathways are often deregulated in prostate tumors with poor prognosis. Here we describe a new genetically engineered mouse model of prostate cancer in which PI3K-Akt-mTOR signaling is activated by inducible disruption of PTEN, and extracellular signal-regulated kinase 1/2 (ERK1/2) MAPK signaling is activated by inducible expression of a BRAF(V600E) oncogene. These tissue-specific compound mutant mice develop lethal prostate tumors that are inherently resistant to castration. These tumors bypass cellular senescence and disseminate to lymph nodes, bone marrow, and lungs where they form overt metastases in approximately 30% of the cases. Activation of PI3K → Akt → mTOR and MAPK signaling pathways in these prostate tumors cooperate to upregulate c-Myc. Accordingly, therapeutic treatments with rapamycin and PD0325901 to target these pathways, respectively, attenuate c-Myc levels and reduce tumor and metastatic burden. Together, our findings suggest a generalized therapeutic approach to target c-Myc activation in prostate cancer by combinatorial targeting of the PI3K → Akt → mTOR and ERK1/2 MAPK signaling pathways.
S89 Bimodal iron oxide nanoparticles for hyperthermia therapy and MR imaging in cancer
Authors: K. L. Parcell, T. L. Kalber, S. Walker-Samuel, P. Southern, Q. A. Pankhurst, M. F. Lythgoe, S. M. Janes
Journal: Thorax (2010)

<h3>Introduction</h3> Super paramagnetic iron oxide nanoparticles (SPION) offer attractive possibilities in biomedicine. Hyperthermia treatment of cancer involves introducing SPION into tumours and applying an alternating magnetic field (AMF). The AMF causes the SPION to heat, resulting in cell death. It has been shown previously that mesenchymal stem cells (MSCs) can be labelled with SPION, with no effect on cell survival, and that they will migrate to and integrate into lung metastases in vivo, following systemic administration. Furthermore, SPION can be used to follow the fate of labelled cells in the body as they cause a marked shortening in T2* on MRI. Therefore, MSCs labelled with SPION offer a promising delivery mechanism for treating lung metastases with hyperthermia therapy. In this preliminary study, the distribution of SPION labelled MSCs and the anti-tumour effect of hyperthermia treatment was evaluated in vitro and in a subcutaneous murine tumour model. <h3>Methods</h3> MSCs were obtained from Tulane University, New Orleans. Cells were incubated overnight in 0.5 mg/ml of the SPION Ferucarbotranfor labelling. Subcutaneous tumours were induced by co-injecting 5 million OVCAR cells and 0.5 million SPION-labelled MSCs. Images of cells within mice were obtained on a 9.4Thorizontal bore Varian NMR system. A 10 mT 1.05 MHz AMF was generated using a copper solenoid coil, diameter 3 cm. Mice were placed inside the coil under anaesthesia and each hyperthermia session lasted 20 min. Post-heating histology was obtained. <h3>Results</h3> Hyperthermia treatment caused a rise in temperature up to 60°C in vitro and a rise in tumour temperature of up to 4°C above body temperature <i>in vivo</i> (Abstract S89 Figure 1), detected by thermal imaging and with fibre optic probes. Iron was confirmed in the tumour using MR imaging and histology. <h3>Discussion</h3> This study demonstrates the potential of SPION to act as an imaging agent and cancer therapy. SPION-labelled MSCs can be imaged in vivo in very low cell numbers. We have demonstrated that the application of an alternating magnetic field causes a temperature rise in these cells, both <i>in vitro</i> and <i>in vivo</i>. In the future, we will optimise SPION as an imaging and hyperthermia agent, for the targeted treatment of lung metastases.
Three Cases of Linear IgA/IgG Bullous Dermatosis Showing IgA and IgG Reactivity With Multiple Antigens, Particularly Laminin-332
Authors: Masanobu Sakaguchi, Toshinori Bito, Yoshiko Oda, Ayuko Kikusawa, Chikako Nishigori, Takichi Munetsugu, Hiroo Yokozeki, Yuri Itotani, Toshiyuki Niguma, Daisuke Tsuruta, Chiharu Tateishi, Norito Ishii, Hiroshi Koga, Takashi Hashimoto
Journal: JAMA Dermatology (2013)

Linear IgA/IgG bullous dermatosis (LAGBD) is a relatively rare autoimmune bullous disease characterized by both IgA and IgG antibodies to epidermal basement membrane zone. The heterogeneity and pathogenesis of the LAGBD autoantigens have not been fully elucidated.We report 3 Japanese cases of LAGBD (ages 81, 88, and 64 years; 1 woman and 2 men). The patients showed bullous and erosive lesions on the trunk and extremities with minimal mucosal lesions. Histopathological analysis revealed a subepidermal blister with neutrophilic infiltration with eosinophils in 2 cases. Direct and indirect immunofluorescence studies disclosed IgG and IgA antibasement membrane zone antibodies. In immunoblot analyses of various antigen sources, all cases showed IgG and IgA antibodies to various subunits of laminin-332, in addition to IgG and IgA reactivity with type VII collagen, laminin-γ1, and BP230 and BP180 recombinant proteins.Our studies revealed that the 3 LAGBD cases showed prominent IgG and IgA reactivity with laminin-332, which was only rarely reported. In addition, all cases showed IgG and IgA reactivity with other multiple antigens, indicating the role of epitope-spreading mechanisms initiated from laminin-332. The significance of IgA antibodies to laminin-332 should be studied in larger cohorts of both LAGBD and linear IgA bullous dermatosis.
Association Between Hospice Use and Depressive Symptoms in Surviving Spouses
Authors: Katherine A. Ornstein, Melissa D. Aldridge, Melissa M. Garrido, Rebecca Gorges, Diane E. Meier, Amy S. Kelley
Journal: JAMA Internal Medicine (2015)

<h3>Importance</h3> Family caregivers of individuals with serious illness are at risk for depressive symptoms and depression. Hospice includes the provision of support services for family caregivers, yet evidence is limited regarding the effect of hospice use on depressive symptoms among surviving caregivers. <h3>Objective</h3> To determine the association between hospice use and depressive symptoms in surviving spouses. <h3>Design, Setting, and Participants</h3> We linked data from the Health and Retirement Study, a nationally representative longitudinal survey of community-dwelling US adults 50 years or older, to Medicare claims. Participants included a propensity score–matched sample of 1016 Health and Retirement Study decedents with at least 1 serious illness and their surviving spouses interviewed between August 2002 and May 2011. We compared the spouses of individuals enrolled in hospice with the spouses of individuals who did not use hospice, performing our analysis between January 30, 2014, and January 16, 2015. <h3>Exposures</h3> Hospice enrollment for at least 3 days in the year before death. <h3>Main Outcomes and Measures</h3> Spousal depressive symptom scores measured 0 to 2 years after death with the Center for Epidemiologic Studies Depression Scale, which is scored from 0 (no symptoms) to 8 (severe symptoms). <h3>Results</h3> Of the 1016 decedents in the matched sample, 305 patients (30.0%) used hospice services for 3 or more days in the year before death. Of the 1016 spouses, 51.9% had more depressive symptoms over time (mean [SD] change, 2.56 [1.65]), with no significant difference related to hospice use. A minority (28.2%) of spouses of hospice users had improved Center for Epidemiologic Studies Depression Scale scores compared with 21.7% of spouses of decedents who did not use hospice, although the difference was not statistically significant (<i>P</i> = .06). Among the 662 spouses who were the primary caregivers, 27.3% of spouses of hospice users had improved Center for Epidemiologic Studies Depression Scale scores compared with 20.7% of spouses of decedents who did not use hospice; the difference was not statistically significant (<i>P</i> = .10). In multivariate analysis, the odds ratio for the association of hospice enrollment with improved depressive symptoms after the spouse's death was 1.63 (95% CI, 1.00-2.65). <h3>Conclusions and Relevance</h3> After bereavement, depression symptoms increased overall for surviving spouses regardless of hospice use. A modest reduction in depressive symptoms was more likely among spouses of hospice users than among spouses of nonhospice users.
Left ventricular systolic function and diastolic filling after intermittent high intensity team sports
Authors: K P George, E Dawson, R E Shave, G Whyte, M Jones, E Hare, D Gaze, P Collinson
Journal: British Journal of Sports Medicine (2004)

Background: Prolonged steady state exercise can lead to a decrease in left ventricular (LV) function as well as promote the release of cardiac troponin T (cTnT). There is limited information on the effect of intermittent high intensity exercise of moderate duration. Objectives: To determine the effect of intermittent high intensity exercise of moderate duration on LV function. Methods: Nineteen male rugby and football players (mean (SD) age 21 (2) years) volunteered. Assessments, before, immediately after, and 24 hours after competitive games, included body mass, heart rate (HR), and systolic blood pressure (sBP) as well as echocardiography to assess stroke volume (SV), ejection fraction (EF), systolic blood pressure/end systolic volume ratio (sBP/ESV), and global diastolic filling (E:A) as well as to indirectly quantify preload (LV internal dimension at end diastole (LVIDd)). Serum cTnT was analysed using a 3rd generation assay. Changes in LV function were analysed by repeated measures analysis of variance. cTnT data are presented descriptively. Results: SV (91 (26) v 91 (36) v 90 (35) ml before, after, and 24 hours after the game respectively), EF (71 (8) v 70 (9) v 71 (7)%), and sBP/ESV (4.2 (1.8) v 3.8 (1.9) v 4.1 (1.6) mm Hg/ml) were not significantly altered (p&gt;0.05). Interestingly, whereas LVIDd was maintained after the game (50 (5) v 50 (6) mm), sBP was transiently but significantly reduced (131 (3) v 122 (3) mm Hg; p&lt;0.05). E:A was moderately (p&lt;0.05) reduced after the game (2.0 (0.4) v 1.5 (0.4)) but returned to baseline within 24 hours. No blood sample contained detectable levels of cTnT. Conclusions: In this cohort, LV systolic function was not significantly altered after intermittent activity. A transient depression in global diastolic filling was partially attributable to a raised HR and could not be explained by myocyte disruption as represented by cTnT release.
<i>ras</i> Mutations Are Associated With Aggressive Tumor Phenotypes and Poor Prognosis in Thyroid Cancer
Authors: Ginesa Garcia-Rostan, Hongyu Zhao, Robert L. Camp, Marina Pollan, Agustin Herrero, Javier Pardo, Ran Wu, Maria Luisa Carcangiu, Jose Costa, Giovanni Tallini
Journal: Journal of Clinical Oncology (2003)

Purpose: ras oncogenic activation has long been demonstrated in thyroid carcinomas of follicular cell derivation, but no consistent relationship has been shown between mutations and clinicopathologic features. Materials and Methods: We analyzed H-, K-, and N-ras mutations by polymerase chain reaction–single-strand conformational polymorphism followed by DNA sequencing in 125 thyroid carcinoma specimens from 107 patients, to include tumors covering the entire spectrum of thyroid tumor differentiation. Results: Mutations were identified in four (8.2%) of 49 well-differentiated carcinomas (WDCs; two [6.7%] of 30 of the tumors were papillary carcinomas, two [10.5%] of 19 of them were follicular carcinomas), in 16 (55.2%) of 29 poorly differentiated carcinomas (PDCs), and in 15 (51.7%) of 29 undifferentiated carcinomas, with a significant association between ras mutation and poorly or undifferentiated tumors (P &lt; .001). Twenty-six (74.3%) of 35 patients with ras-mutated tumors died as a result of disease as opposed to 23 (31.9%) of 72 patients with tumors lacking the mutations. Among patients with differentiated thyroid carcinomas (WDC and PDC), 11 (55.0%) of 20 patients with mutated tumors died as a result of disease as opposed to nine (15.5%) of 58 patients with wild-type ras tumors, and the correlation was independent of tumor differentiation and stage (P = .016). K-ras codon 13 mutations (all with G-A nucleotide transitions resulting in Gly&gt;Asp substitution) and single activating mutations in any of the ras genes were also independent predictors of poor survival in differentiated thyroid carcinomas (P = .027 and P = .007, respectively). Conclusion: These findings demonstrate that ras mutations are a marker for aggressive cancer behavior and indicate a possible role of ras genotyping to identify thyroid carcinoma subsets associated with poor prognosis.
Chronic rhino-sinusitis in severe asthma improves at high altitude
Authors: Lucia H. Rijssenbeek-Nouwens, Karin F. Fieten, Adriaan O. Bron, Els J. Weersink, Elisabeth H. Bel
Journal: European Respiratory Journal (2011)

Background:  Severe asthma and chronic rhino-sinusitis often coexist (Meltzer, JACI 2004). Patients with severe asthma have shown to benefit from high altitude treatment (Rijssenbeek AJRCCM 2010). It is unknown whether chronic rhino-sinusitis also improves at high altitude.   Aim:  To investigate the effect of high altitude treatment on symptoms of upper and lower airways disease in patients with severe asthma and rhino-sinusitis.   Methods:  137 patients with severe asthma treated at the Dutch Asthmacenter Davos were included. In 65 patients, using nasal steroids, sino-nasal symptoms (SNOT scores), asthma control (ACQ), exhaled Nitric Oxide (FeNO), use of oral and nasal steroids were analysed, as well as the relationship between parameters of upper and lower airways. Parametric and non-parametric tests were used where appropriate.  The improvement in SNOT-20 correlated significantly with the improvement in ACQ (R=0.527, p   Conclusions:  A simultaneous improvement in upper and lower airway symptoms and oral steroid use occurs at high altitude in patients with severe asthma and chronic rhino-sinusitis.   Implications:  These beneficial effects on upper airways disease underscore the anti-inflammatory and steroid-sparing effect of high altitude treatment in patients with severe asthma.
Hepatic oleate uptake. Electrochemical driving forces in intact rat liver.
Authors: R A Weisiger, J G Fitz, B F Scharschmidt
Journal: Journal of Clinical Investigation (1989)

Recent observations suggest that the hepatic uptake of oleate may be sodium coupled. To assess the electrochemical forces driving fatty acid uptake, we used microelectrodes to monitor continuously the electrical potential difference across the plasma membrane in the perfused rat liver while simultaneously monitoring the rate of tracer [3H]oleate uptake from 1% albumin solutions. Isosmotic cation or anion substitution was used to vary the potential difference over the physiologic range. Depolarization of cells from -29 to -19 mV by substituting gluconate for chloride reduced steady-state oleate uptake by 34%. Conversely, hyperpolarization of cells to -52 mV by substituting nitrate for chloride increased uptake by 41%. Replacement of perfusate sodium with choline depolarized the cells to -18 mV and reduced uptake by 58%, an amount greater than expected from the degree of depolarization alone. Oleate in higher concentrations (1.5 mM in 2% albumin) depolarized cells by 3 mV in the presence of sodium, but had no effect in sodium-free buffer. These results suggest that a portion of oleate uptake in the intact liver occurs by electrogenic sodium cotransport. Uptake appears to be driven by both the electrical and sodium chemical gradients across the plasma membrane.