tbuckley/cabot-search huggingface dataset:
Association of Dorsolateral Prefrontal Cortex Dysfunction With Disrupted Coordinated Brain Activity in Schizophrenia: Relationship With Impaired Cognition, Behavioral Disorganization, and Global Function
Authors: Jong H. Yoon, Michael J. Minzenberg, Stefan Ursu, Ryan Walters, Carter Wendelken, J. Daniel Ragland, Cameron S. Carter
Journal: American Journal of Psychiatry (2008)

Objective: Although deficits in cognitive control are thought to contribute to the diverse cognitive and behavioral abnormalities in individuals with schizophrenia, the neural mechanisms underlying these deficits remain unclear. In this event-related functional magnetic resonance imaging (fMRI) study, the authors tested the hypothesis that during cognitive control tasks, impaired activation of the dorsolateral prefrontal cortex in schizophrenia patients is associated with disrupted coordinated activity between this prefrontal region and a distributed brain network that supports cognitive control. Method: Through the use of an event-related design, 25 patients with first-episode schizophrenia and 24 healthy comparison subjects, matched on demographic characteristics, were assessed while performing a version of the AX continuous performance task. Functional neuroimaging data were analyzed using 1) univariate (region-of-interest blood-oxygen-level-dependent [BOLD] time series and whole brain voxel-wise regression) analysis to confirm the presence of dorsolateral prefrontal cortex dysfunction and 2) multivariate analysis to examine dorsolateral prefrontal cortex functional connectivity. In addition, correlations between dorsolateral prefrontal cortex functional connectivity and the following variables were investigated: clinical symptoms, task performance, and coordinated brain activity associated with cognitive control. Results: Schizophrenia patients exhibited a specific deficit in cognitive control, with significantly reduced accuracy in the BX condition relative to any other condition. Univariate fMRI revealed dorsolateral prefrontal cortex dysfunction during the high cognitive control condition. Multivariate analysis revealed significant impairment in functional connectivity between the dorsolateral prefrontal cortex and task-relevant brain regions. Significant correlations were also found between dorsolateral prefrontal cortex functional connectivity and cognitive performance, behavioral disorganization, and global functioning. Conclusions: These findings suggest that there is an association between decreased dorsolateral prefrontal cortex activity and connectivity and a task-related neural network. This deficit in coordinated brain activity may result in the disabling disorganization symptoms related to impaired cognition in individuals with schizophrenia.
Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells
Authors: Agnes Basseville, Laurence Preisser, Sophie de Carné Trécesson, Michèle Boisdron-Celle, Erick Gamelin, Olivier Coqueret, Alain Morel
Journal: Molecular Cancer (2011)

Abstract Background Resistance to chemotherapy remains one of the principle obstacles to the treatment of colon cancer. In order to identify the molecular mechanism of this resistance, we investigated the role of the steroid and xenobiotic receptor (SXR) in the induction of drug resistance. Indeed, this nuclear receptor plays an important role in response to xenobiotics through the upregulation of detoxification genes. Following drug treatments, SXR is activated and interacts with the retinoid X receptor (RXR) to induce expression of some genes involved in drug metabolism such as phase I enzyme (like CYP), phase II enzymes (like UGT) and transporters (e.g. MDR1). Results In this study, we have shown that endogenous SXR is activated in response to SN-38, the active metabolite of the anticancer drug irinotecan, in human colon cancer cell lines. We have found that endogenous SXR translocates into the nucleus and associates with RXR upon SN-38 treatment. Using ChIP, we have demonstrated that endogenous SXR, following its activation, binds to the native promoter of the CYP3A4 gene to induce its expression. RNA interference experiments confirmed SXR involvement in CYP3A4 overexpression and permitted us to identify CYP3A5 and MRP2 transporter as SXR target genes. As a consequence, cells overexpressing SXR were found to be less sensitive to irinotecan treatment. Conclusions Altogether, these results suggest that the SXR pathway is involved in colon cancer irinotecan resistance in colon cancer cell line via the upregulation of select detoxification genes.
The case for statins: has it really been made?
Authors: A. Thompson, N. J Temple
Journal: Journal of the Royal Society of Medicine (2004)

Statin drugs are a modern success story.They are the medical treatment for coronary disease and the star of the pharmaceutical industry.Worldwide, sales of statins are running at about $19 billion a year and growing quickly. 1 This success profits not only the pharmaceutical industry but also all those whose finances and careers are furthered by the research and the sales.But to what extent is it also a success for the general public?To answer this we will look at the major long-term (five to six year) clinical trials of statins.We start with the treatment offered to the participants, then look at the endpoints that were selected, and continue with a look at how the results have been reported.We conclude with a discussion of the costeffectiveness of statins for people at different levels of risk of coronary heart disease (CHD).
Fracture incidence after 3 years of aromatase inhibitor therapy
Authors: B. Bouvard, P. Soulié, E. Hoppé, M. Georgin-Mege, M. Royer, N. Mesgouez-Nebout, C. Lassalle, P. Cellier, E. Jadaud, S. Abadie-Lacourtoisie, C. Tuchais, S. Vinchon-Petit, M. Audran, D. Chappard, E. Legrand
Journal: Annals of Oncology (2014)
Estimates of mean alveolar gas in patients with chronic airways obstruction
Authors: A Giannella-Neto, P Paoletti, E Fornai, C Giuntini
Journal: European Respiratory Journal (1989)

Alveolar to arterial differences (AaD) may be computed from representative alveolar gas pressures (PA). These are particularly difficult to obtain in patients with chronic airways obstruction (CAO) and severe inhomogeneity of the ventilation/perfusion (VA/Q) ratio. In 25 such patients, using a computerized mass spectrometer, representative values of alveolar gas were obtained: 1. as end-tidal concentrations (ET); 2. using the alveolar air equation with PACO2 derived from Bohr's equation (BE); 3. putting PACO2 = PACO2 into the alveolar air equation to compute ideal O2 alveolar pressure (ID); 4. applying Rahn's definition of "mean" alveolar gas (RD), i.e. taking within each jth breath, the alveolar pressures corresponding to the moment when the instantaneous gas exchange ratio R(t)j equals the overall exchange ratio for that breath Rj. During quiet breathing, the point where R(t)j equals Rj occurred at 71% of tidal volume (VT). Alveolar pressures by BE and RD resulted in similar values (115.5 +/- 6.9 and 115.5 +/- 6.6 mmHg for O2 and 30.3 +/- 5.7 and 30.8 +/- 5.7 mmHg for CO2, respectively), but they were significantly different from those by ET and ID (106.2 +/- 9.5 and 95.6 +/- 13.5 mmHg for O2 and 36.3 +/- 7.7 and 48.2 +/- 11.2 mmHg for CO2, respectively). These findings may be explained considering that PA(BE) and PA(RD) represent both high and low VA/Q units, whereas PA(ET) and PA(ID) represent mainly low VA/Q units. AaDCO2 by RD and BE appeared proportional to the severity of CAO as estimated from VT. Automated techniques make it possible to substitute end-tidal determinations with more accurate estimates either by measuring anatomical dead-space and using Bohr's equation or by applying Rahn's definition.
Phacomatosis pigmentovascularis type IIa successfully treated with two types of laser therapy
Authors: I. Ono, T. Tateshita
Journal: British Journal of Dermatology (2000)

We describe a 28-year-old Japanese woman with phacomatosis pigmentovascularis type IIa who was treated by 27 sessions of Q-switched ruby laser irradiation to the site of dermal melanosis on her face and three sessions of dye laser irradiation to the port-wine stain on her left cheek. This is the first report of the successful treatment of a cutaneous lesion in a patient with phacomatosis pigmentovascularis. As the outcome of the treatments was excellent, we conclude that phacomatosis pigmentovascularis type IIa can be treated successfully by the combination of the two types of laser therapy.
Voltage-dependent gating and single-channel conductance of adult mammalian atrial gap junctions.
Authors: R Lal, M F Arnsdorf
Journal: Circulation Research (1992)

In the heart, the rapid propagation and synchronization of action potentials necessary for a normal heart rhythm and an effective cardiac output are mediated by specialized ionic channels that link adjacent cells and are known collectively as gap junctions. Cardiac gap junctions are gated by various physiological and pharmacological agents, but the role of voltage in their gating is unclear. Whereas embryonic or neonatal ventricular cells have voltage-gated gap junctions, adult cells are reported to have only voltage-independent gap junctions. We studied the voltage dependence of adult rat atrial gap junctions by individually voltage clamping each cell of a connected cell pair and controlling the transjunctional voltage (Vj), measuring transjunctional current (Ij), and calculating junctional conductance (gj). Two distinct populations of cell pairs were observed: highly coupled pairs with the peak gjs ranging from 3.4 to 40 nS and weakly coupled pairs with the peak gjs ranging from 0.3 to 2.0 nS. gj was dependent on Vj, and Ij decayed exponentially, with the time constants being voltage dependent. Voltage dependence was most apparent when cells were poorly coupled. The gj did not decrease to zero. The normalized conductance--Vj plot was fit with a two-state Boltzmann model as a first approximation, resulting in a half-inactivation potential and gating charge of 42.5 mV and 1.14 eV, respectively, for the weakly coupled cell pairs. For highly coupled cell pairs, the half-inactivation potential shifted to 53.3 mV. Single gap junctional channels had a gj of 36.2 +/- 7.6 pS (range, 27-49 pS), which was Vj independent.(ABSTRACT TRUNCATED AT 250 WORDS)
Evolution of radiographic damage in ankylosing spondylitis: a 12 year prospective follow-up of the OASIS study
Authors: Sofia Ramiro, Carmen Stolwijk, Astrid van Tubergen, Désirée van der Heijde, Maxime Dougados, Filip van den Bosch, Robert Landewé
Journal: Annals of the Rheumatic Diseases (2013)

Objectives To describe the evolution of radiographic abnormalities of the spine in patients with ankylosing spondylitis (AS). Methods Patients with AS were followed prospectively with 2 yearly radiographs for 12 years. The modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) was scored by two readers (R1 and R2). New syndesmophytes at uninvolved vertebral corners were computed. Radiographic progression was investigated using generalised estimating equations. Results 809 radiographs (presenting 520 at 2 yearly intervals) from 186 patients (70% men, mean age 43 (SD 12) years, mean 20 (SD 12) years since symptom onset and 83% HLA-B27 positive) were included. Mean mSASSS at baseline was 11.6 (16.2). While the course of progression in individual patients was highly variable, and still occurred in patients with decades of symptom duration, mean 2 year progression was 2.0 (3.5) mSASSS units. Over the entire follow-up, at least one new syndesmophyte was found in 55% (R1) and 63% (R2) of patients (38% (R1) and 39% (R2) of all intervals). In 24% of patients (39% of intervals), there was no progression. A progression ≥5 mSASSS units occurred in 22% of patients (or in 12% of intervals). At the group level, a linear time course model fitted the data best, with a constant rate over the entire 12 year interval of 0.98 mSASSS units/year. Radiographic progression occurred significantly faster in men, in HLA-B27 positive patients and in patients with a baseline mSASSS≥10. Conclusions Long term radiographic progression in AS is highly variable in the individual patient, more severe in HLA-B27 positive men and still occurs after decades of disease. At the group level, however, progression in AS follows an approximately linear course.
Pooled Analysis of a Self-Sampling HPV DNA Test as a Cervical Cancer Primary Screening Method
Authors: F.-H. Zhao, A. K. Lewkowitz, F. Chen, M. J. Lin, S.-Y. Hu, X. Zhang, Q.-J. Pan, J.-F. Ma, M. Niyazi, C.-Q. Li, S.-M. Li, J. S. Smith, J. L. Belinson, Y.-L. Qiao, P. E. Castle
Journal: JNCI Journal of the National Cancer Institute (2012)

Worldwide, one-seventh of cervical cancers occur in China, which lacks a national screening program. By evaluating the diagnostic accuracy of self-collected cervicovaginal specimens tested for human papillomavirus (HPV) DNA (Self-HPV testing) in China, we sought to determine whether Self-HPV testing may serve as a primary cervical cancer screening method in low-resource settings. We compiled individual patient data from five population-based cervical cancer–screening studies in China. Participants (n = 13 140) received Self-HPV testing, physician-collected cervical specimens for HPV testing (Physician-HPV testing), liquid-based cytology (LBC), and visual inspection with acetic acid (VIA). Screen-positive women underwent colposcopy and confirmatory biopsy. We analyzed the accuracies of pooled Self-HPV testing, Physician-HPV testing, VIA, and LBC to detect biopsy-confirmed cervical intraepithelial neoplasia grade 2 or more severe (CIN2+) and CIN3+. All statistical tests were two-sided. Of 13 004 women included in the analysis, 507 (3.9%) were diagnosed as CIN2+, 273 (2.1%) as CIN3+, and 37 (0.3%) with cervical cancer. Self-HPV testing had 86.2% sensitivity and 80.7% specificity for detecting CIN2+ and 86.1% sensitivity and 79.5% specificity for detecting CIN3+. VIA had statistically significantly lower sensitivity for detecting CIN2+ (50.3%) and CIN3+ (55.7%) and higher specificity for detecting CIN2+ (87.4%) and CIN3+ (86.9%) (all P values < .001) than Self-HPV testing, LBC had lower sensitivity for detecting CIN2+ (80.7%, P = .015), similar sensitivity for detecting CIN3+ (89.0%, P = .341), and higher specificity for detecting CIN2+ (94.0%, P < .001) and CIN3+ (92.8%, P < .001) than Self-HPV testing. Physician-HPV testing was more sensitive for detecting CIN2+ (97.0%) and CIN3+ (97.8%) but similarly specific for detecting CIN2+ (82.7%) and CIN3+ (81.3%) (all P values <.001) than Self-HPV testing. The sensitivity of Self-HPV testing compared favorably with that of LBC and was superior to the sensitivity of VIA. Self-HPV testing may complement current screening programs by increasing population coverage in settings that do not have easy access to comprehensive cytology-based screening.
The Treatment of Large Tuberculous Abscess Associated with Bone Disease by Evacuation and Injection with a Solution of Iodoform in Ether
Authors: A. W. M. Robson
Journal: BMJ (1891)

too hiiglh, but more especially dturinc the first decade.Thus, of 60 cases of spinal disease uinder 10 years of ace treated as out-patients only '9 suippurated wlhile undler my observationl.This increasing severity of tlhe dlisease in join-t cases as age advances is nio doubt to a large extent due to the increasing proportioni of cases in wlhiel the disease commences pri- marily in thle hone, and also the greater frequency of sequestra over soft caseat in g(leposits.Sex is another imnportalnt factor.Tlhus, in our 386 patients undler treatImienit in hospital, 25-)1, or 65 per ceint.were males, an(d 1:35, or :35 per cent., females.This is a fact wlhielh is noted by iiost antithoirs, altlhouiglh the relative percentages of the two sexes may he somewhat (lifferently giveni.In the case of the spine tHe stateernnts are the most cointra(lictory.The relationi of the sexe(s varies at different ages, as is realdily seen oln referringz to tlie former table.Tlhus, of the total number of cases admitted, 11.3 per cent.were rnales and 8.8 per cent.were females at or below 5 years of age, etc., females being thus dlistinietly less susceptible than naless, but especially so abov-e 10 years of age.Tihe predispositioni of the sexes to disease als-o varies according" to the joint in question, as seen in tllis table, where ((ex(c(epting tlhe shoulder-joint, wlhere the number of cases was too few) we see that the numbers most nearly approacwh each othler in the case of the knee-joint, 57.6 per cent.being males and 42.4 per cenit.females, and are farthmest apart in the case of the tarsus, whiere 85.8 per cent.are males and 14.2 per (erit.females.
Survival after aortic valve replacement forsevere aortic stenosis with low transvalvular gradients and severe left ventricular dysfunction
Authors: Jeremy J. Pereira, Michael S. Lauer, Mohammad Bashir, Imran Afridi, Eugene H. Blackstone, William J. Stewart, Patrick M. McCarthy, James D. Thomas, Craig R. Asher
Journal: Journal of the American College of Cardiology (2002)
MCT-1 Oncogene Contributes to Increased <i>In vivo</i> Tumorigenicity of MCF7 Cells by Promotion of Angiogenesis and Inhibition of Apoptosis
Authors: Anait S. Levenson, Kenneth E. Thurn, Laura A. Simons, Dorina Veliceasa, Jennifer Jarrett, Clodia Osipo, V. Craig Jordan, Olga V. Volpert, Robert L. Satcher, Ronald B. Gartenhaus
Journal: Cancer Research (2005)

Abstract Overexpression of a novel oncogene MCT-1 (multiple copies in a T cell malignancy) causes malignant transformation of murine fibroblasts. To establish its role in the pathogenesis of breast cancer in humans, we generated stable transfectants of MCF7 breast cancer cells negative for endogenous MCT-1 (MCF7-MCT-1). Overexpression of MCT-1 in these cells resulted in a slight elevation of estrogen receptor-α, and higher rates of DNA synthesis and growth in response to estradiol compared with the empty vector control (MCF7-EV). The pure antiestrogen fulvestrant inhibited the estradiol-stimulated proliferation of MCF7-MCT-1 cells. The MCF7-MCT-1 clones showed increased invasiveness in the presence of 50% serum compared with the MCF7-EV. In a tumor xenograft model, MCT-1–overexpressing cells showed higher take rates and formed significantly larger tumors than MCF7-EV controls. When we examined angiogenic phenotype and molecular mediators of angiogenesis in MCF7-MCT-1 tumors in vivo, we found greater microvascular density and lower apoptosis in the MCF7-MCT-1 tumors compared with MCF7-EV controls accompanied by a dramatic decline in the levels of angiogenesis inhibitor, thrombospondin-1 (TSP1). In vitro, blocking TSP1 in the medium conditioned by MCT-1–negative cells restored its angiogenic potential to that of the MCF7-MCT-1 cells. Conversely, despite an increase in mRNA encoding vascular endothelial growth factor upon MCT-1 overexpression, vascular endothelial growth factor protein levels have not been notably altered. Taken together, our results suggest that MCT-1 may contribute to the pathogenesis and progression of human breast cancer via at least two routes: promotion of angiogenesis through the decline of TSP1 and inhibition of apoptosis.
High incidence of exercise-induced bronchoconstriction in triathletes of the Swiss national team * COMMENTARY
Authors: Bruno H Knöpfli, Mona Luke-Zeitoun, Serge P von Duvillard, Adrian Burki, Christian Bachlechner, Heidi Keller
Journal: British Journal of Sports Medicine (2007)

To assess the progression of bronchial reactivity (BR) and incidence of bronchial hyperreactivity (BH), exercise-induced bronchoconstriction (EIB) and asthma in triathletes over 2 years.Subjects were seven athletes from the Swiss national triathlon team (mean (SD) age 24.3 (4.8) years), who initially were not asthmatic, not treated with antiasthmatic medication, and who had performed at international level for more than 3 consecutive years (2001-2003). To assess BR, BH and EIB, subjects ran on a 400 m track for 8 min at intensities equal to the anaerobic threshold. Tests were conducted in ambient temperatures of 4.4 (2.8) degrees C, -8.8 (2.4) degrees C and 3.6 (1.5) degrees C, and humidity of 52 (16)%, 83 (13)% and 93 (2)%. Forced expiratory volume in 1 s (FEV(1)) was measured before and at 2, 5, 10 and 15 min after EIB, and 5 min after inhalation of a beta2 agonist. Two methods were used to calculate the incidence: (1) the standard assessment; (2) extrapolation of the decrease in FEV(1) to the BH limit.BR increased significantly in the seven athletes (FEV(1): year, p = 0.04; year x EIB, p = 0.002; EIB p<0.001). Within 2 years, BR had increased significantly and even reached BH in some athletes. Three athletes exhibited BH. After extrapolation of the decrease in FEV(1) in all seven athletes, the limit of 10% by definition for BH was determined to occur within 1.77-4.81 years, resulting in 21-57% of athletes with newly developed BH per year.Athletes develop EIB quickly, a rate of increase 195-286 times that of the normal rate for development of asthma.
Critical role of the Toll-like receptor signal adaptor protein MyD88 in acute allograft rejection
Authors: Daniel R. Goldstein, Bethany M. Tesar, Shizuo Akira, Fadi G. Lakkis
Journal: Journal of Clinical Investigation (2003)

The Toll-like receptors (TLRs) are recently discovered germline-encoded receptors on APCs that are critically important in innate immune recognition of microbial pathogens. However, their role in solid-organ transplantation is unknown. To explore this role, we employed a skin allograft model using mice with targeted deletion of the universal TLR signal adaptor protein, MyD88. We report that minor antigen-mismatched (HY-mismatched) allograft rejection cannot occur in the absence of MyD88 signaling. Furthermore, we show that the inability to reject these allografts results from a reduced number of mature DCs in draining lymph nodes, leading to impaired generation of anti-graft-reactive T cells and impaired Th1 immunity. Hence, this work demonstrates that TLRs can be activated in a transplant setting and not solely by infections. These results link innate immunity to the initiation of the adaptive alloimmune response.
Association of decreased myocardial beta-receptors and chronotropic response to isoproterenol and exercise in pigs following chronic dynamic exercise.
Authors: H K Hammond, F C White, L L Brunton, J C Longhurst
Journal: Circulation Research (1987)

The effects of chronic dynamic exercise on myocardial beta-adrenergic and muscarinic cholinergic receptors and chronotropic sensitivity to isoproterenol were studied in 5 Yucatan miniswine. Right atrial and left ventricular biopsies, heart rate responses to isoproterenol, and maximal exercise treadmill testing were obtained before and after 10-19 weeks of treadmill running. Radioligand studies using 125I-iodocyanopindolol (ICYP) and 3H-quinuclidinyl benzilate (QNB) were used to determine the number of beta-adrenergic and muscarinic cholinergic receptors. Maximal oxygen consumption increased from 52 +/- 5 to 65 +/- 7 ml/kg/min (mean +/- SD; p less than 0.02), maximal workload from 530 +/- 111 to 1,074 +/- 179 KPM/min (p less than 0.01), resting heart rate decreased from 91 +/- 13 to 62 +/- 4 beats/min (p less than 0.01), heart rate at 75% of pretraining maximal workload decreased from 253 +/- 15 to 196 +/- 12 beats/min (p less than 0.01), and maximal exercise heart rate decreased from 273 +/- 6 to 254 +/- 9 beats/min (p less than 0.01). Decreased heart rate responsiveness to adrenergic stimulation was observed following chronic exercise. Maximal isoproterenol-stimulated heart rate decreased from 225 +/- 13 to 185 +/- 28 beats/min (p less than 0.05) and the slope of the isoproterenol dose-response relation decreased from 63 +/- 16 to 40 +/- 16 (p less than 0.05). Radioligand studies revealed a decrease in beta-receptor number in the right atrium following chronic exercise (61 +/- 9 vs. 34 +/- 8 fmol/mg; p less than 0.02), but receptor number in membranes from the left ventricle did not change (60 +/- 9 vs. 62 +/- 4 fmol/mg).(ABSTRACT TRUNCATED AT 250 WORDS)