tbuckley/cabot-search huggingface dataset:
The intra-articular distribution of 90yttrium does not influence the clinical outcome of radiation synovectomy of the knee
Authors: Z N Jahangier, F M van der Zant, J W G Jacobs, H G Riedstra, G M M Gommans, J F Verzijlbergen, J W J Bijlsma, J W van Isselt
Journal: Annals of the Rheumatic Diseases (2007)

<b>Objectives:</b> To assess the impact of the intra-articular distribution of <sup>90</sup>yttrium-citrate (<sup>90</sup>Y) on the clinical effect of radiosynoviorthesis (RSO) of the knee and on <sup>90</sup>Y leakage from this joint. <b>Methods:</b> Patients with arthritis of the knee received 185 MBq <sup>90</sup>Y combined with a glucocorticoid, followed by clinical bed rest. Intra-articular <sup>90</sup>Y distribution, measured with a dual-head gamma camera immediately or after 24 hours, was scored as mainly diffuse or mainly focal. Leakage to regional lymph nodes, the liver and spleen was assessed with a dual-head gamma camera after 24 hours. Clinical effect was scored after 6 months by a composite change index (CCI), range 0–12; responders were defined as having a CCI ⩾6. <b>Results:</b> Seventy-eight knees of 69 patients, mostly suffering from undifferentiated arthritis (42%) or RA (28%), were treated. <sup>90</sup>Y distribution was mainly diffuse in 54% and mainly focal in 46% with clinical response rates of 40% versus 56%, respectively, p = 0.3. CCI was not correlated with distribution. <sup>90</sup>Y leakage was found only to the liver and the spleen (mean leakage 0.4% and 1.1%, respectively). Leakage was significantly less in case of diffuse intra-articular <sup>90</sup>Y distribution, whereas leakage to the liver was correlated with distribution (r = 0.68, p&lt;0.001). <sup>90</sup>Y leakage was not correlated with CCI. <b>Conclusions:</b> Intra-articular <sup>90</sup>Y distribution does not influence the clinical effect of RSO of the knee. Although <sup>90</sup>Y leakage from the joint is less if <sup>90</sup>Y distributes diffusely in the joint cavity, leakage does not seem to hamper the clinical effect.
Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study
Authors: Costagliola, D, Lodwick, R, Ledergerber, B, Torti, C, van Sighem, A, Podzamczer, D, Mocroft, A, Dorrucci, M, Masquelier, B, DE LUCA, Andrea, Jansen, K, De Wit, S, Obel, N, Fätkenheuer, G, Touloumi, G, Mussini, C, Castagna, A, Stephan, C, García, F, Zangerle, R, Duval, X, Perez Hoyos, S, Meyer, L, Ghosn, J, Fabre Colin, C, Kjaer, J, Chene, G, Garup, J, Phillips, A.
Journal: The Lancet Infectious Diseases (2011)

Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09.In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF.28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend was not significant after adjustment (p=0·22).A substantial improvement in viral load suppression and accompanying decrease in the rates of AIDS in people after extensive failure to drugs from the three original antiretroviral classes during 2000-09 was probably mainly driven by availability of newer drugs with better tolerability and ease of use and small cross-resistance profiles, suggesting the public health benefit of the introduction of new drugs.
Malignant vascular tumours of the pleura in "asbestos" workers and endothelial differentiation in malignant mesothelioma
Authors: R L Attanoos
Journal: Thorax (2000)

Three cases of diffuse malignant vascular tumours of the pleura are described which mimicked malignant mesothelioma clinically and pathologically (so called "pseudomesothelioma"). All had occupational histories of exposure to asbestos. The relationship of these tumours to mesothelioma and asbestos exposure is discussed.To examine the histogenetic relationship between mesothelioma and these three tumours an immunohistochemical analysis of vascular marker (CD31, CD34, and Von Willebrand factor) expression was undertaken in 92 cases of pleural mesothelioma, in addition to these three tumours. Electron microscopic fibre analysis of lung tissue was performed on each of the three cases to assess asbestos fibre content.Diffuse pleural epithelioid haemangioendotheliomas may closely resemble malignant mesothelioma clinically and pathologically but, of the 92 pleural mesotheliomas tested, none showed expression of CD31, CD34, and Von Willebrand factor. Although all three cases had claimed exposure to asbestos, ferruginous bodies typical of asbestos were only seen by light microscopy in case 2, and only in this subject was the asbestos fibre content raised in comparison with the range seen in a non-exposed background population. The latent period in the pleural epithelioid haemangioendotheliomas ranged from 18 to 60 years.Endothelial differentiation does not appear to occur in mesothelioma and therefore should be clearly separated from it. No definite association between pleural epithelioid haemangioendothelioma and exposure to asbestos can be made from this small series but further investigation is warranted.
Is depression a dysfunction in self-regulating the brain/behavior system for approach?
Authors: Timothy J. Strauman
Journal: Behavioral and Brain Sciences (1999)

This commentary examines the implications of the Depue &amp; Collins model for the etiology and treatment of depression, specifically, whether it can account for findings concerning neurobiological, behavioral, and phenomenological facets of depression. Drawing upon the construct of self-regulation, I explore the fit of the model to current knowledge about depression, conceptualized as a dysfunction within a hypothetical brain/behavior system for maximizing positive outcomes.
Her2-Targeted Therapies in Non–Small Cell Lung Cancer
Authors: Charles Swanton, Andy Futreal, Tim Eisen
Journal: Clinical Cancer Research (2006)

Abstract Sensitivity to Her2-directed therapies is complex and involves expression not only of Her2 but also of other epidermal growth factor receptor (EGFR) family members, their ligands, and molecules that influence pathway activity, such as insulin-like growth factor-1 receptor, PTEN, and p27. The EGFR experience has taught us that responses can easily be diluted in an unselected cohort of patients. To date, trials of Her2-targeted therapies, such as trastuzumab, have been insufficiently powered to determine whether patients with non–small cell lung cancer (NSCLC) with Her2 gene amplification (rather than overexpression by immunohistochemistry) may benefit from these agents. It is unclear whether agents targeting Her2 might prove successful in future clinical trials in a highly selected patient cohort, either with Her2 amplification or Her2 gene mutations. The frequency of Her2 mutations in NSCLC may be too low to justify a prospective clinical trial in this patient group. The frequency of Her2 amplification (2-23%) in NSCLC and the widespread availability of Her2 fluorescence in situ hybridization analysis may justify a final study of trastuzumab monotherapy in this patient population. The role played by Her2 as the obligate heterodimerization partner for the other EGFR family members renders Her2 an attractive target irrespective of receptor overexpression. The most promising Her2-targeted strategy will likely prove to be combinatorial approaches using an EGFR tyrosine kinase inhibitor together with Her2 dimerization inhibitors.
Recombinant human interleukin 10 suppresses gliadin dependent T cell activation in ex vivo cultured coeliac intestinal mucosa
Authors: V M Salvati
Journal: Gut (2004)

<b>Background:</b> Enteropathy in coeliac disease (CD) is sustained by a gliadin specific Th1 response. Interleukin (IL)-10 can downregulate Th1 immune responses. <b>Aim:</b> We investigated the ability of recombinant human (rh) IL-10 to suppress gliadin induced Th1 response. <b>Patients and methods:</b> IL-10 RNA transcripts were analysed by competitive reverse transcription-polymerase chain reaction in duodenal biopsies from untreated and treated CD patients, non-coeliac enteropathies (NCE), and controls. CD biopsies were cultured with a peptic-tryptic digest of gliadin with or without rhIL-10. The proportion of CD80+ and CD25+ cells in the lamina propria, epithelial expression of Fas, intraepithelial infiltration of CD3+ cells, as well as cytokine synthesis (interferon γ (IFN-γ) and IL-2) were measured. Short term T cell lines (TCLs) obtained from treated CD biopsies cultured with gliadin with or without rhIL-10 were analysed by ELISPOT for gliadin specific production of IFN-γ. <b>Results:</b> In untreated CD and NCE, IL-10 RNA transcripts were significantly upregulated. In ex vivo organ cultures, rhIL-10 downregulated gliadin induced cytokine synthesis, inhibited intraepithelial migration of CD3+ cells, and reduced the proportion of lamina propria CD25+ and CD80+ cells whereas it did not interfere with epithelial Fas expression. In short term TCLs, rhIL-10 abrogated the IFN-γ response to gliadin. <b>Conclusions:</b> rhIL-10 suppresses gliadin specific T cell activation. It may interfere with the antigen presenting capacity of lamina propria mononuclear cells as it reduces the expression of CD80. Interestingly, rhIL-10 also induces a long term hyporesponsiveness of gliadin specific mucosal T cells. These results offer new perspectives for therapeutic strategies in coeliac patients based on immune modulation by IL-10.
The acoustic properties of snores
Authors: R Beck, M Odeh, A Oliven, N Gavriely
Journal: European Respiratory Journal (1995)

This study was undertaken in an attempt to characterize the acoustic properties of snoring sounds in the time and frequency domains, and to correlate between these properties and the mechanical events underlying their production. Three experimental set-ups were used: 1) Dog model--six mongrel dogs, in which partial upper airway obstruction was created by an implanted supraglottic balloon. Flow, supraglottic pressure, and snoring sounds were recorded during different degrees of obstruction. Fifteen to 20 snores from each dog (total 100 snores) were analysed. 2) Simulated human snores--Six simulated snores from each of four subjects were recorded in two locations (trachea and ambient) with simultaneous airflow, and their correlations examined. 3) Snoring patients--snores were recorded with an ambient microphone from nine subjects with "heavy" snoring and no obstructive sleep apnoea (OSA). Forty to 50 snores from each subject were analysed (total of 400 snores). The snoring sound was analysed in the time (time-expanded waveform) and frequency (power spectrum) domains. After analysing these snores, we were able to identify two dominant patterns which are distinctly different from each other: the "simple-waveform" and the "complex-waveform". The complex-waveform snore is characterized by repetitive, equally-spaced, train of sound structures, starting with a large deflection followed by a decaying amplitude wave. In the frequency domain, it is characterized by multiple, equally-spaced peaks of power (comb-like spectrum). Simple-waveform snores have a quasi-sinusoidal waveform, with a range of variants, and almost no secondary internal oscillations. Their power spectrum contains only 1-3 peaks, of which the first is the most prominent. We developed a mathematical representation of these waveforms, which is presented along with its implications. The complex-waveform snores result from colliding of the airway walls and represent actual brief airway closure. Simple-waveform snores are of higher frequency and probably result from oscillation around a neutral position without actual closure of the lumen.
Modulation by Dietary Salt of Verapamil Disposition in Humans
Authors: Dawood Darbar, Martin F. Fromm, Simonetta Dell’Orto, Richard B. Kim, Heyo K. Kroemer, Michel Eichelbaum, Dan M. Roden
Journal: Circulation (1998)

Background —The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism. Methods and Results —Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d) diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed. Plasma concentrations of both unlabeled enantiomers (ie, from oral therapy) were significantly ( P &lt;0.05) lower during the high-salt phase (eg, mean area under the time-concentration curve [0 to 12 hours] for S -verapamil: 7765±2591 ng · min · mL −1 [high salt] versus 12 514±3527 ng · min · mL −1 [low salt], P &lt;0.05). Peak plasma concentrations were significantly lower and the extent of PR interval prolongation significantly blunted with the high-salt diet. In contrast, data with labeled drug (ie, reflecting the intravenous route) were nearly identical for the 2 diets. Conclusions —These data indicate that a clinically important component of presystemic drug disposition occurs at the prehepatic (presumably intestinal) level and is sensitive to dietary salt.
Meticillin-resistant Staphylococcus aureus with a novel mecA homologue in human and bovine populations in the UK and Denmark: a descriptive study
Authors: Laura García-Álvarez, Matthew TG Holden, Heather Lindsay, Cerian R Webb, Derek FJ Brown, Martin D Curran, Enid Walpole, Karen Brooks, Derek J Pickard, Christopher Teale, Julian Parkhill, Stephen D Bentley, Giles F Edwards, E Kirsty Girvan, Angela M Kearns, Bruno Pichon, Robert LR Hill, Anders Rhod Larsen, Robert L Skov, Sharon J Peacock, Duncan J Maskell, Mark A Holmes
Journal: The Lancet Infectious Diseases (2011)
In vivo persistence of adoptively transferred TCR gene-transduced lymphocytes with anti-tumor reactivity in patients with MAGE-A4 expressing esophageal cancer
Authors: Hiroaki Ikeda, Shinichi Kageyama, Naoko Imai, Yoshihiro Miyahara, Mikiya Ishihara, Naoyuki Katayama, Hirofumi Yoshioka, Daisuke Tomura, Ikuei Nukaya, Junichi Mineno, Kazuto Takesako, Hiroshi Shiku
Journal: Journal for ImmunoTherapy of Cancer (2013)

Meeting abstracts The application of adoptive immunotherapy with tumor-specific T cells has been limited because of the short life span of the transferred T cells unless the host has been manipulated. Engineering the antigen receptor gene in patients’ lymphocytes is one promising strategy to
Reliance on end-expiratory wedge pressure leads to misclassification of pulmonary hypertension
Authors: Barbara L. LeVarge, Eugene Pomerantsev, Richard N. Channick
Journal: European Respiratory Journal (2014)

Current guidelines recommend measurement of pulmonary artery wedge pressure (PAWP) at end-expiration. However, this recommendation is not universally followed and may not be physiologically appropriate. We investigated the performance of end-expiratory PAWP in the evaluation of precapillary pulmonary hypertension patients. 329 spontaneously breathing patients undergoing right heart catheterisation were retrospectively classified as having a precapillary, post-capillary or mixed phenotype based on standardised clinical criteria. Tracings were reviewed to compare end-expiratory PAWP with PAWP averaged throughout the respiratory cycle; these values were correlated with the clinical classifications. Predictors of large respirophasic variation in PAWP were determined. Elevated end-expiratory PAWP (&gt;15 mmHg) occurred in 29% of subjects with precapillary phenotype. There were no differences in demographics or clinical history between those with elevated and normal end-expiratory PAWP. Those with elevated end-expiratory PAWP had greater right atrial pressure and respirophasic PAWP variation. Among all subjects, the magnitude of respirophasic variation in PAWP was positively correlated with body mass index and respirophasic variation in left ventricular end-diastolic pressure. A significant proportion of precapillary pulmonary hypertension patients have end-expiratory PAWP &gt;15 mmHg. Spontaneous positive end-expiratory intrathoracic pressure may contribute; in those cases, PAWP averaged throughout respiration may be a more accurate measurement.
Targeted Axl Inhibition Primes Chronic Lymphocytic Leukemia B Cells to Apoptosis and Shows Synergistic/Additive Effects in Combination with BTK Inhibitors
Authors: Sutapa Sinha, Justin Boysen, Michael Nelson, Charla Secreto, Steven L. Warner, David J. Bearss, Connie Lesnick, Tait D. Shanafelt, Neil E. Kay, Asish K. Ghosh
Journal: Clinical Cancer Research (2015)

B-cell chronic lymphocytic leukemia (CLL) is an incurable disease despite aggressive therapeutic approaches. We previously found that Axl receptor tyrosine kinase (RTK) plays a critical role in CLL B-cell survival. Here, we explored the possibility of using a high-affinity Axl inhibitor as a single agent or in combination with Bruton's tyrosine kinase (BTK) inhibitors for future clinical trial to treat patients with CLL.Expression/activation status of other members of the TAM (e.g., Tyro3, Axl, and MER) family of RTKs in CLL B cells was evaluated. Cells were treated with a high-affinity orally bioavailable Axl inhibitor TP-0903 with or without the presence of CLL bone marrow stromal cells (BMSCs). Inhibitory effects of TP-0903 on the Axl signaling pathway were also evaluated in CLL B cells. Finally, cells were exposed to TP-0903 in combination with BTK inhibitors to determine any synergistic/additive effects of the combination.CLL B cells overexpress Tyro3, but not MER. Of interest, Tyro3 remains as constitutively phosphorylated and forms a complex with Axl in CLL B cells. TP-0903 induces massive apoptosis in CLL B cells with LD50 values of nanomolar ranges. Importantly, CLL BMSCs could not protect the leukemic B cells from TP-0903-induced apoptosis. A marked reduction of the antiapoptotic proteins Mcl-1, Bcl-2, and XIAP and upregulation of the proapoptotic protein BIM in CLL B cells was detected as a result of Axl inhibition. Finally, combination of TP-0903 with BTK inhibitors augments CLL B-cell apoptosis.Administration of TP-0903 either as a single agent or in combination with BTK inhibitors may be effective in treating patients with CLL.
Two visual systems and two theories of perception: An attempt to reconcile the constructivist and ecological approaches
Authors: Joel Norman
Journal: Behavioral and Brain Sciences (2002)

The two contrasting theoretical approaches to visual perception, the constructivist and the ecological, are briefly presented and illustrated through their analyses of space and size perception. Earlier calls for their reconciliation and unification are reviewed. Neurophysiological, neuropsychological, and psychophysical evidence for the existence of two quite distinct visual systems, the ventral and the dorsal, is presented. These two perceptual systems differ in their functions; the ventral system's central function is that of identification, while the dorsal system is mainly engaged in the visual control of motor behavior. The strong parallels between the ecological approach and the functioning of the dorsal system, and between the constructivist approach and the functioning of the ventral system are noted. It is also shown that the experimental paradigms used by the proponents of these two approaches match the functions of the respective visual systems. A dual-process approach to visual perception emerges from this analysis, with the ecological-dorsal process transpiring mainly without conscious awareness, while the constructivist-ventral process is normally conscious. Some implications of this dual-process approach to visual-perceptual phenomena are presented, with emphasis on space perception.
Abnormal Rich Club Organization and Functional Brain Dynamics in Schizophrenia
Authors: Martijn P. van den Heuvel, Olaf Sporns, Guusje Collin, Thomas Scheewe, René C. W. Mandl, Wiepke Cahn, Joaquín Goñi, Hilleke E. Hulshoff Pol, René S. Kahn
Journal: JAMA Psychiatry (2013)

The human brain forms a large-scale structural network of regions and interregional pathways. Recent studies have reported the existence of a selective set of highly central and interconnected hub regions that may play a crucial role in the brain's integrative processes, together forming a central backbone for global brain communication. Abnormal brain connectivity may have a key role in the pathophysiology of schizophrenia.To examine the structure of the rich club in schizophrenia and its role in global functional brain dynamics.Structural diffusion tensor imaging and resting-state functional magnetic resonance imaging were performed in patients with schizophrenia and matched healthy controls.Department of Psychiatry, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht, Utrecht, the Netherlands.Forty-eight patients and 45 healthy controls participated in the study. An independent replication data set of 41 patients and 51 healthy controls was included to replicate and validate significant findings. MAIN OUTCOME(S) AND MEASURES: Measures of rich club organization, connectivity density of rich club connections and connections linking peripheral regions to brain hubs, measures of global brain network efficiency, and measures of coupling between brain structure and functional dynamics.Rich club organization between high-degree hub nodes was significantly affected in patients, together with a reduced density of rich club connections predominantly comprising the white matter pathways that link the midline frontal, parietal, and insular hub regions. This reduction in rich club density was found to be associated with lower levels of global communication capacity, a relationship that was absent for other white matter pathways. In addition, patients had an increase in the strength of structural connectivity-functional connectivity coupling.Our findings provide novel biological evidence that schizophrenia is characterized by a selective disruption of brain connectivity among central hub regions of the brain, potentially leading to reduced communication capacity and altered functional brain dynamics.