tbuckley/cabot-search huggingface dataset:
The Dimethyltryptamine-Forming Enzyme in Blood Platelets: A Study in Monozygotic Twins Discordant for Schizophrenia
Authors: RICHARD JED WYATT, JUAN M. SAAVEDRA, ROBERT BELMAKER, STEPHEN COHEN, WILLIAM POLLIN
Journal: American Journal of Psychiatry (1973)

Samples of the nondialyzed platelets of l4 pairs of monozygotic twins discordant for schizophrenia were assayed for their ability to enzymatically form the hallucinogen dimethyltryptamine. The schizophrenic twins had higher mean levels of enzyme activity than their non-schizophrenic co-twins, whose mean level of enzyme activity was equal to that of 22 normal subjects. This finding suggests that the higher levels of enzyme activity found in schizophrenics is produced by their environment and is not genetically determined.
Protection by recombinant alpha 1-antitrypsin Ala357 Arg358 against arterial hypotension induced by factor XII fragment.
Authors: M Schapira, M A Ramus, B Waeber, H R Brunner, S Jallat, D Carvallo, C Roitsch, M Courtney
Journal: Journal of Clinical Investigation (1987)

The specificity of serpin superfamily protease inhibitors such as alpha 1-antitrypsin or C1 inhibitor is determined by the amino acid residues of the inhibitor reactive center. To obtain an inhibitor that would be specific for the plasma kallikrein-kinin system enzymes, we have constructed an antitrypsin mutant having Arg at the reactive center P1 residue (position 358) and Ala at residue P2 (position 357). These modifications were made because C1 inhibitor, the major natural inhibitor of kallikrein and Factor XIIa, contains Arg at P1 and Ala at P2. In vitro, the novel inhibitor, alpha 1-antitrypsin Ala357 Arg358, was more efficient than C1 inhibitor for inhibiting kallikrein. Furthermore, Wistar rats pretreated with alpha 1-antitrypsin Ala357 Arg358 were partially protected from the circulatory collapse caused by the administration of beta-Factor XIIa.
Regulation of Clinical Research Sponsored by Pharmaceutical Companies: A Proposal
Authors: Julio Sotelo
Journal: PLoS Medicine (2006)

Drug development is indispensable to deal effectively with disease [ 1]. However, two dilemmas emerge from clinical research devoted to this goal. First, new drugs are the source of a huge economy ruled not by the standards of the medical profession, but by the rules of business and the market [ 2]. Second, although the testing and the medical community's “blessing” of a new drug lie entirely in the hands of medical institutions, medical journals, and regulatory agencies [ 3], once the drug is approved the ruthless mechanisms of industry propaganda and commerce take over [ 4, 5]. 

The gains in health obtained by the advent of a new drug should always be considered according to the crucial concept of its cost–benefit balance, and the benefits often fall far below the costs (either monetary or otherwise). Of course, patients and drug companies might have different feelings about the costs and benefits of a new drug: patients have high expectations that the drug will help them to recover their health, whereas companies rely mostly on statistical arguments to back up the superiority of their new drug over existing ones [ 2, 3].
Using tests for recent infection to estimate incidence: problems and prospects for HIV
Authors: A Welte, T A McWalter, O Laeyendecker, T B Hallett
Journal: Eurosurveillance (2010)

Tests for recent infection (TRIs), such as the BED assay, provide a convenient way to estimate HIV incidence rates from cross-sectional survey data. Controversy has arisen over how the imperfect performance of a TRI should be characterised and taken into account. Recent theoretical work is providing a unified framework within which to work with a variety of TRI- and epidemic-specific assumptions in order to estimate incidence using imperfect TRIs, but suggests that larger survey sample sizes will be required than previously thought. This paper reviews the framework qualitatively and provides examples of estimator performance, identifying the characteristics required by a TRI to estimate incidence reliably that should guide the future development of TRIs.
Recruitment Maneuvers in Three Experimental Models of Acute Lung Injury
Authors: THOMAS E.VAN der KLOOT, LLUIS BLANCH, A. MELYNNE YOUNGBLOOD, CRAIG WEINERT, ALEX B. ADAMS, JOHN J. MARINI, ROBERT S. SHAPIRO, AVI NAHUM
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Recruitment maneuvers (RM), consisting of sustained inflations at high airway pressures, have been advocated as an adjunct to mechanical ventilation in acute respiratory distress syndrome (ARDS). We studied the effect of baseline ventilatory strategy and RM on end-expiratory lung volume (EELV) and oxygenation in 18 dogs, using three models of acute lung injury (ALI; n = 6 in each group): saline lavage (LAV), oleic acid injury (OAI), and intratracheal instillation of Escherichia coli (pneumonia; PNM). All three models exhibited similar degrees of lung injury. The PNM model was less responsive to positive end-expiratory pressure (PEEP) than was the LAV or OAI model. Only the LAV model showed an oxygenation response to increasing tidal volume (Vt). After RM, there were transient increases in PaO2 and EELV when ventilating with PEEP = 10 cm H2O. At PEEP = 20 cm H2O the lungs were probably fully recruited, since the plateau airway pressures were relatively high ( ≈ 45 cm H2O) and the oxygenation was similar to preinjury values, thus making the system unresponsive to RM. Sustained improvement in oxygenation after RM was seen in the LAV model when ventilating with PEEP = 10 cm H2O and Vt = 15 ml/kg. Changes in EELV correlated with changes in PaO2 only in the OAI model with PEEP = 10 cm H2O. We conclude that responses to PEEP, Vt, and RM differ among these models of ALI. RM may have a role in some patients with ARDS who are ventilated with low PEEP and low Vt.
The adherence of human Fc receptor-bearing lymphocytes to antigen-antibody complexes. II. Morphologic alterations induced by the substrate.
Authors: E Alexander, P Henkart
Journal: The Journal of Experimental Medicine (1976)

The adhesion of human Fc receptor-bearing lymphocytes to immobilized antigen-antibody complexes is accompanied by marked alterations in cell shape, resulting in flattening of greater than 90% of the adherent cells. In addition, about 65% of the adherent cells become elongated, with distinct uropods being present in about 1/3 of these cells. Scanning electron microscopy demonstrates that most of the surface microvilli are lost, while ruffled membranes and long microextensions are formed during the shape change. Time-lapse cinematography shows that the major shape changes occur within a few minutes after contact with the substrate, and that the adherent cells undergo translational motility. Both flattening and elongation of the adherent cells are inhibited by low temperature, chelating agents, cytochalasin B, and vinblastine, while sodium azide selectively inhibits elongation and uropod formation. It is argued that these morphological changes result from an active response of the cell to the immobilized complexes, and that such alterations may be related mechanistically to the ability of the cells to kill antibody-coated target cells.
Finland's Galapagos: Founder effect, drift, and isolation in the inheritance of susceptibility alleles
Authors: Tom Campbell, Daria Osipova, Seppo Kähkönen
Journal: Behavioral and Brain Sciences (2006)

The target article excludes ancestral neutrality as a cause for the inheritance of schizophrenia, with an argument relating to selection against a single allele in the Finnish population. However, drift would predominate over selection within subisolates of the Finnish population. Comparisons of subisolates with heterogeneous populations may provide clues to the endophenotypic structure of complex polygenetic heritable mental disorders.
Evaluation of de novo transcriptome assemblies from RNA-Seq data
Authors: Bo Li, Nathanael Fillmore, Yongsheng Bai, Mike Collins, James A Thomson, Ron Stewart, Colin N Dewey
Journal: Genome biology (2014)

Abstract De novo RNA-Seq assembly facilitates the study of transcriptomes for species without sequenced genomes, but it is challenging to select the most accurate assembly in this context. To address this challenge, we developed a model-based score, RSEM-EVAL, for evaluating assemblies when the ground truth is unknown. We show that RSEM-EVAL correctly reflects assembly accuracy, as measured by REF-EVAL, a refined set of ground-truth-based scores that we also developed. Guided by RSEM-EVAL, we assembled the transcriptome of the regenerating axolotl limb; this assembly compares favorably to a previous assembly. A software package implementing our methods, DETONATE, is freely available at http://deweylab.biostat.wisc.edu/detonate .
Detection of Lymph Node Metastases by Gadolinium-Enhanced Magnetic Resonance Imaging: Systematic Review and Meta-analysis
Authors: Wenche M. Klerkx, Leon Bax, Wouter B. Veldhuis, A. Peter M. Heintz, Willem PThM. Mali, Petra H. M. Peeters, Karel G. M. Moons
Journal: JNCI Journal of the National Cancer Institute (2010)

Gadolinium-based contrast agents are used with magnetic resonance imaging (MRI) to highlight tumor vascularity in organs. They are also widely used for primary tumor visualization. We conducted a systematic review and meta-analysis of the existing evidence of the accuracy of gadolinium-enhanced MRI for staging lymph node metastases.We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for studies published in English or German from January 1, 1988, to January 1, 2008, that assessed the diagnostic accuracy of gadolinium-enhanced MRI in the evaluation of lymphatic metastases compared with histopathologic examination as the reference test. Based on a priori-defined clinical considerations, we studied three subgroups of studies: those that used a single malignancy criterion and those that used multiple malignancy criteria with or without contrast highlighting. Summaries of MRI sensitivity and specificity for detecting lymph node metastases were calculated using a bivariate regression model. All statistical tests were two-sided.The literature search yielded 43 full-text papers that were considered for inclusion in the meta-analysis. We performed quantitative pooled analyses on the 32 studies that provided data on patient-level diagnosis. The weighted estimates of sensitivity and specificity for all studies combined were 0.72 (95% confidence interval [CI] = 0.66 to 0.79) and 0.87 (95% CI = 0.82 to 0.91). Estimates of sensitivity and specificity were essentially unchanged for studies that used a single malignancy criterion (0.71 [95% CI = 0.61 to 0.79] and 0.88 [95% CI = 0.80 to 0.93], respectively; n = 11 studies) or multiple malignancy criteria without contrast enhancement (0.70 [95% CI = 0.58 to 0.79] and 0.86 [95% CI = 0.68 to 0.94], respectively; n = 6 studies). The sensitivity increased to 0.84 (95% CI = 0.70 to 0.92), with a specificity of 0.82 (95% CI = 0.72 to 0.89) for the nine studies that incorporated contrast enhancement in their multiple malignancy criteria. Six studies did not define the malignancy criteria they used.The overall accuracy of gadolinium-enhanced magnetic resonance imaging for the detection of nodal metastases is moderate. Incorporating contrast enhancement in the malignancy criteria substantially improves the accuracy of this diagnostic test.
MRI and the diagnosis of multiple sclerosis: expanding the concept of “no better explanation”
Authors: Arnaud Charil, Tarek A Yousry, Marco Rovaris, Frederik Barkhof, Nicola De Stefano, Franz Fazekas, David H Miller, Xavier Montalban, Jack H Simon, Chris Polman, Massimo Filippi
Journal: The Lancet Neurology (2006)
NI-29 * DIAGNOSIS OF PSEUDOPROGRESSION IN PATIENTS WITH GLIOBLASTOMA USING AMINO ACID PET
Authors: N. Galldiks, V. Dunkl, G. Stoffels, M. Hutterer, M. Rapp, S. Kebir, R. Goldbrunner, M. I. Ruge, M. Schmidt, K.-J. Langen
Journal: Neuro-Oncology (2014)

BACKGROUND: The follow-up of glioblastoma patients may be difficult with conventional MRI since reactive blood-brain barrier alterations with contrast enhancement can mimick tumor progression (“pseudoprogression”), especially early after completion of radiochemotherapy. METHODS: Twenty-six glioblastoma patients with newly appearance or an increase of enhancing lesions (>25%) on standard MRI with gadolinium-based contrast agents within the first 12 weeks after completion of radiochemotherapy with concomitant temozolomide (median time, 7 weeks) were additionally examined by amino acid PET using O-(2-[18F]fluoroethyl)-L-tyrosine (18F-FET) (n = 22) or 11C-methyl-L-methionine (11C-MET) (n = 4). Median duration between MR and amino acid PET imaging was 7 d. Maximum and mean tumor/brain ratios (TBRmax/mean) of 18F-FET and 11C-MET uptake were determined. Furthermore, 18F-FET uptake kinetic parameters (i.e., time-to-peak and patterns of the time-activity curves (TAC)) were evaluated. The presence of pseudoprogression / early tumor progression was based on the clinical course (progression-free survival (PFS) > / ≤ 6 mo) and/or histopathological findings. Imaging results were also related to overall survival (OS). RESULTS: Pseudoprogression was confirmed in 14 of 26 patients. TBRmax and TBRmean of 18F-FET / 11C-MET uptake were significantly higher in patients with early tumor progression (n = 12) than in patients with pseudoprogression (TBRmax, 3.6 ± 0.8 vs. 2.4 ± 0.4; TBRmean, 2.5 ± 0.3 vs. 1.8 ± 0.2; both P < 0.001). Furthermore, patterns of TAC were significantly different in both groups (P = 0.04) and presence of MGMT promoter methylation was significantly higher in patients with pseudoprogression (P = 0.02). Receiver-operating-characteristic analysis yielded a TBRmax of 2.9 as an optimal cut-off to identify early tumor progression (sensitivity, 92%; specificity, 93%; accuracy, 92%; AUC, 0.96 ± 0.04; P < 0.001). Univariate survival analyses revealed that a TBRmax < 2.9 predicted both a significantly longer PFS (median PFS, 21 vs. 5 months; P < 0.001) and OS (median OS, 33 vs. 12 months; P = 0.007). CONCLUSIONS: Amino acid PET contributes significantly in diagnosing pseudoprogression.
Eat well to get well
Authors: E F M Wouters
Journal: Thorax (2003)

Nutrition and energy supply are important components of rehabilitation programmes for patients with COPD.

Improvement in functional performance is considered an important management goal in patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation is now considered as an evidence based intervention to achieve an improvement in functional capacity as well as other management goals such as improved health status and reduction in breathlessness.1 Although exercise training is considered the core component of every pulmonary rehabilitation programme, the optimal method of exercise training as well as the optimal training intensity remains a matter of debate. Standard recommendations for exercise training in healthy subjects are generally transferred to disabled patients with COPD, and the complexity of the disease related changes which make an important contribution to the functional disability experienced is usually ignored.

The metabolic demand of exercise, reflected in the energy expended on activities, is generally overlooked when patients are stressed to increase their activity level. Consideration of energy balance in COPD is important because weight loss and, specifically loss in fat mass, is the result of a negative energy balance. During the last decade most attention has been focused on resting energy expenditure in patients with COPD; in many of these patients hypermetabolism can be demonstrated which is partly related to the level of systemic inflammation.2,3 However, in normal subjects the energy expenditure for activities is the most variable component of total energy expenditure. While studies in other chronic wasting diseases characterised by hypermetabolism and systemic inflammation—for example, cancer, chronic heart failure, AIDS—have shown an adaptive decrease in activity induced energy expenditure so that total daily energy expenditure is normal, increased activity induced and total daily energy expenditure has been measured in free living ambulatory COPD patients.4 Great variations in total energy expenditure, physical activity, …
Lack of prophylaxis before the onset of acute venous thromboembolism among hospitalized cancer patients: the SWIss Venous ThromboEmbolism Registry (SWIVTER)
Authors: N. Kucher, D. Spirk, I. Baumgartner, L. Mazzolai, W. Korte, D. Nobel, M. Banyai, H. Bounameaux
Journal: Annals of Oncology (2009)
RHAMM expression and isoform balance predict aggressive disease and poor survival in multiple myeloma
Authors: Christopher A. Maxwell, Erik Rasmussen, Fenghuang Zhan, Jonathan J. Keats, Sophia Adamia, Erin Strachan, Mary Crainie, Ronald Walker, Andrew R. Belch, Linda M. Pilarski, Bart Barlogie, John Shaughnessy, Tony Reiman
Journal: Blood (2004)
Thrombospondin-platelet interactions. Role of divalent cations, wall shear rate, and platelet membrane glycoproteins.
Authors: F R Agbanyo, J J Sixma, P G de Groot, L R Languino, E F Plow
Journal: Journal of Clinical Investigation (1993)

The role of thrombospondin, a multifunctional matrix glycoprotein, in platelet adhesion is controversial: both adhesive and antiadhesive properties have been attributed to this molecule. Because shear flow has a significant influence on platelet adhesion, we have assessed thrombospondin-platelet interactions both under static and flow conditions. The capacity of thrombospondin to support platelet adhesion depended upon its conformation. In a Ca(2+)-depleted conformation, such as in citrated plasma, thrombospondin was nonadhesive or antiadhesive as it inhibited platelet adhesion to fibrinogen, fibronectin, laminin, and von Willebrand factor by 30-70%. In a Ca(2+)-replete conformation, however, thrombospondin effectively supported platelet adhesion. Shear rate influenced this adhesion; percent surface coverage on thrombospondin increased from 5.4 +/- 0.3 at 0 s-1 to 41.5 +/- 6.7 at 1,600 s-1. In contrast to the extensive platelet spreading observed on fibronectin at all shear rates, platelet spreading on thrombospondin occurred only sporadically and at high shear rates. GPIa-IIa, GPIIb-IIIa, GPIV, and the vitronectin receptor, which are all proposed platelet receptors for thrombospondin, were not solely responsible for platelet adhesion to thrombospondin. These results suggest that thrombospondin may play a dual role in adhesive processes in vivo: (a) it may function in conjunction with other adhesive proteins to maintain optimal platelet adhesion at various shear rates; and (b) it may serve as a modulator of cellular adhesive functions under specific microenvironmental conditions.
Circulating Aminopeptidase N/CD13 Is an Independent Prognostic Factor in Patients with Non–Small Cell Lung Cancer
Authors: Haruyasu Murakami, Akihito Yokoyama, Keiichi Kondo, Shuhei Nakanishi, Nobuoki Kohno, Masayuki Miyake
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Aminopeptidase N, also known as CD13, has important roles in tumor metastasis and angiogenesis. Its expression in tumor tissue has been reported to be associated with poor prognosis. However, the clinical significance of circulating aminopeptidase N/CD13 in patients with solid tumors is unknown. We previously developed an aminopeptidase N/CD13–specific monoclonal antibody (mAb) MH8-11, which inhibits cell motility and angiogenesis in vitro. The aim of this study was to evaluate the clinical significance of circulating aminopeptidase N/CD13 protein detected by mAb MH8-11 in patients with non–small cell lung cancer (NSCLC). Experimental Design: We used electrochemiluminescence immunoassay with mAb MH8-11 to determine circulating aminopeptidase N/CD13 levels in 90 healthy volunteers and 90 patients with NSCLC. Circulating aminopeptidase N/CD13 levels were measured in sera taken before treatment and evaluated for a relationship with clinical outcomes. Results: A significant correlation was found between tumor progression and serum aminopeptidase N/CD13 concentrations (r = 0.23, P = 0.029). High serum aminopeptidase N/CD13 levels (n = 17) were associated with advanced stage (P = 0.004) or poor performance status (P = 0.001). The overall survival rate for patients with high serum aminopeptidase N/CD13 levels (n = 17) was significantly less than that of patients with low serum aminopeptidase N/CD13 levels (n = 73, P &amp;lt; 0.0001). In a multivariate survival analysis in patients with NSCLC, serum aminopeptidase N/CD13 levels had an independent influence on survival (relative risk, 4.1; 95% confidence interval, 1.9-8.8). Conclusions: Our data suggest that a high level of circulating aminopeptidase N/CD13 at diagnosis is an independent prognostic factor in patients with NSCLC.
High-level inhibition of mitochondrial complexes III and IV is required to increase glutamate release from the nerve terminal
Authors: Seán M Kilbride, Sonia A Gluchowska, Jayne E Telford, Catherine O'Sullivan, Gavin P Davey
Journal: Molecular Neurodegeneration (2011)

The activities of mitochondrial complex III (ubiquinol-cytochrome c reductase, EC 1.10.2.2) and complex IV (cytochrome c oxidase EC 1.9.3.1) are reduced by 30-70% in Huntington's disease and Alzheimer's disease, respectively, and are associated with excitotoxic cell death in these disorders. In this study, we investigated the control that complexes III and complex IV exert on glutamate release from the isolated nerve terminal.Inhibition of complex III activity by 60-90% was necessary for a major increase in the rate of Ca2+-independent glutamate release to occur from isolated nerve terminals (synaptosomes) depolarized with 4-aminopyridine or KCl. Similarly, an 85-90% inhibition of complex IV activity was required before a major increase in the rate of Ca2+-independent glutamate release from depolarized synaptosomes was observed. Inhibition of complex III and IV activities by ~ 60% and above was required before rates of glutamate efflux from polarized synaptosomes were increased.These results suggest that nerve terminal mitochondria possess high reserves of complex III and IV activity and that high inhibition thresholds must be reached before excess glutamate is released from the nerve terminal. The implications of the results in the context of the relationship between electron transport chain enzyme deficiencies and excitotoxicity in neurodegenerative disorders are discussed.
Electroanatomic Mapping of Entrained and Exit Zones in Patients With Repaired Congenital Heart Disease and Intra-Atrial Reentrant Tachycardia
Authors: John K. Triedman, Mark E. Alexander, Charles I. Berul, Laura M. Bevilacqua, Edward P. Walsh
Journal: Circulation (2001)

Background —Characterization of reentrant circuits and targeting ablation sites remains difficult for intra-atrial reentrant tachycardias (IART) in congenital heart disease (CHD). Methods and Results —Electroanatomic mapping and entrainment pacing were performed before successful ablation of 18 IART circuits in 15 patients with CHD. Principal features of IART circuits were atrial septal defect (4 patients), atriotomy (3 patients), other atrial scar (3 patients), crista terminalis (3 patients), and right atrioventricular valve (5 patients). A median of 176 sites (range, 96 to 317 sites) was mapped for activation and 13 sites (range, 9 to 28 sites) for entrainment response. Postpacing intervals within 20 ms of tachycardia cycle length and stimulus–to–P-wave intervals of 0 to 90 ms (exit zones) were mapped to atrial surfaces generated by electroanatomic mapping. Criteria for entrainment were met over a median of 21 cm 2 of atrial surface (range, 2 to 75 cm 2 ), 19% (range, 1% to 81%) of total area tested. Using integrated data, relations between activation sequence and protected corridor of conduction could be inferred for 16 of 17 IARTs. Successful ablation was achieved at a site distant from the putative protected corridor in 9 of 18 (50%) circuits. Conclusions —The right atrium in CHD supports a variety of IART mechanisms. Fusion of activation and entrainment data provided insight into specific IART mechanisms relevant to ablation.