tbuckley/cabot-search huggingface dataset:
Thalamo-Cortical Activation and Connectivity During Response Preparation in Adults With Persistent and Remitted ADHD
Authors: Suzanne M. Clerkin, Kurt P. Schulz, Olga G. Berwid, Jin Fan, Jeffrey H. Newcorn, Cheuk Y. Tang, Jeffrey M. Halperin
Journal: American Journal of Psychiatry (2013)

Objective The neural correlates of stimulus-driven processes, such as response preparation, have been posited to be associated with the onset of attention deficit hyperactivity disorder (ADHD) while being distinct from the neural mechanisms associated with recovery. The authors tested this hypothesis in adults with remitted and persistent ADHD. Method Thirty-eight young adults who were diagnosed with combined-type ADHD in childhood (probands) and 32 carefully matched comparison subjects were followed longitudinally and scanned with functional MRI while performing an event-related cued reaction time task. Probands were characterized as individuals with persistent or remitted ADHD. Differences in thalamo-cortical activation and functional connectivity during response preparation between comparison subjects and probands and between individuals with persistent ADHD and those with remitted ADHD were assessed by contrasting neural activation and functional connectivity during cue or noncue events. Results Probands exhibited less cue-related activation than comparison subjects in the thalamus, anterior cingulate cortex, supplementary motor area, inferior parietal lobe, and dorsolateral prefrontal cortex despite similar overall patterns of activation. There were no differences in activation between individuals in the remitted ADHD group and those in the persistent ADHD group in any hypothesized regions. However, cue-related functional connectivity between the right thalamus and brainstem was greater in comparison subjects relative to probands, and cue-related connectivity was greater between the right thalamus and prefrontal regions in individuals with remitted ADHD relative to those with persistent ADHD. Conclusions Decreased thalamo-cortical activation during response preparation was present in adults diagnosed with ADHD in childhood regardless of symptom remission in adulthood, and may be partly driven by less functional coordination between the brainstem and thalamus. Greater functional integration of the thalamo-cortical network might parallel symptom recovery.
TCT-69 PEPCAD-DES: A randomized, multicenter, single blinded trial comparing paclitaxel coated balloon angioplasty with plain balloon angioplasty in drug-eluting-stent restenosis – 12 months results
Authors: Harald Rittger, Johannes Brachmann, Matthias Waliszewski, Ralf Birkemeyer, Christoph Garlichs, Jochen Wöhrle
Journal: Journal of the American College of Cardiology (2012)
The DispatchTM catheter as a delivery tool for arterial gene transfer
Authors: O Tahlil
Journal: Cardiovascular Research (1997)

Objective: Most currently available percutaneous delivery methods for arterial gene therapy are limited by the need for a long incubation period, which may lead to unacceptable tissue ischemia, especially in the coronary vasculature. Conversely, shorter incubation times may result in inefficient gene transfer, especially in atheromatous arteries. A new local delivery autoperfusion multichamber catheter is now available which permits local delivery in the coronary arterial system without inducing myocardial ischemia. The present study aimed at evaluating the performance of this catheter for achieving arterial gene transfer using replication-defective adenoviral vectors in normal and atheromatous arteries. Methods: A replication-defective adenoviral vector carrying a nuclear-targeted β-galactosidase reporter gene (Ad-RSVβgal, 5.10[9] plaque-forming units [pfu]) was delivered to the iliac arteries of normal (n = 7) and atheromatous (1% cholesterol diet + arterial abrasion) (n = 6) rabbits, via a multichamber autoperfusion balloon catheter (DispatchTM, SciMed). Duration of gene delivery was 60 min. Results: Three days later, marked expression of the reporter gene was detected by histochemistry in the endothelium at the delivery site (percentage of transfected cells: 16 ± 8% /artery (range 11–25%). There was a low transduction rate in medial smooth muscle cells 0.7 ± 0.4% /artery (range 0.3–1.1%). In atheromatous arteries, transduction was consistently achieved in the superficial layers of the neointima but was lower (1.1 ± 0.5% /artery, range 0.3–1.7%). Transgene expression was detected by histochemistry in the liver of 3/13 animals, suggesting that there is a substantial risk of systemic dissemination of the viral vectors. Conclusion: Efficient arterial gene delivery to endothelial and superficial smooth muscle cells is feasible using local delivery of adenoviral vectors via the DispatchTM autoperfusion catheter, in both normal and atheromatous arteries. This perfusion catheter may be a useful tool for coronary artery gene transfer.
Idiotypic regulation of the immune system. Common idiotypic specificities between idiotypes and antibodies raised against anti-idiotypic antibodies in rabbits.
Authors: M Winkler, J D Franssen, C Collignon, O Leo, B Mariamé, P van de Walle, D de Groote, J Urbain
Journal: The Journal of Experimental Medicine (1979)

Anti-idiotypic antibodies (Ab2) were raised in allotype-matched rabbits against anti-carbohydrate or anti-tobacco mosaic virus antibodies (Ab1). Several Ab2 were purified and injected into a third series of rabbits III which synthesized antiantiidiotypic antibodies (Ab3). Antigen was then given for the first time in those rabbits who had synthesized Ab3. The specific antibody synthesized in rabbits III was called Ab1'. Anti-idiotypic antibodies were raised against purified Ab3 antibodies (Ab4). In most cases, Ab1' antibodies are sharing idiotypic specificities with Ab1. Ab3 did not react with antigen but shared idiotopes with Ab1 and Ab1' because Ab4 antibodies, which are anti-idiotypes to Ab3 do recognize specifically Ab1 and Ab1' antibodies belonging to the same chain of immunization. It seems therefore that Ab3 looks idiotypically like Ab1 and Ab4 displays the same behaviour as Ab2. A general view of the functioning of the immune system is presented.
A Crucial Role for Cellular Retinol-Binding Protein I in Retinoid Signaling
Authors: R. Lotan
Journal: JNCI Journal of the National Cancer Institute (2005)

Retinol (the prototypic vitamin A) and its metabolites called retinoids play important physiologic roles in embryonal development, vision, maintenance of epithelial differentiation, immune functions, and reproduction (1). Many of these functions are mediated by retinol metabolites such as all-trans-retinoic acid (ATRA) (2). ATRA modulates gene expression by means of nuclear receptors that are members of the steroid hormone gene superfamily. These receptors, retinoic acid receptors (RARs) and retinoid X receptors (RXRs), appear in at least three subtypes, designated , , and . The receptors function as ligand-activated heterodimeric DNA-binding transcription enhancing factors and regulate the transcription of various genes, which play important roles during development and in adult tissues. Abberant expression and function of specific retinoid receptors, primarily RAR , have been associated with cancer development and progression (3,4). However, recent studies have highlighted additional mechanisms for abrogation of retinoid signaling in carcinogenesis. These involve abnormalities located upstream of retinoic acid and its nuclear receptors. These defects interfere with retinol storage and its metabolism to retinoic acid and result in a localized retinoid deficiency. Interestingly, we have suggested that decreased levels of RAR may be, at least in part, caused by local vitamin A deficiency (5). Dietary retinol is stored in the liver in specialized cells and delivered to various target tissues via a retinol-binding protein
Overactive Performance Monitoring as an Endophenotype for Obsessive-Compulsive Disorder: Evidence From a Treatment Study
Authors: Anja Riesel, Tanja Endrass, Lea Antonia Auerbach, Norbert Kathmann
Journal: American Journal of Psychiatry (2015)

Objective: Overactive performance monitoring, as measured by the error-related negativity in the event-related brain potential, represents one of the most robust psychophysiological alterations in obsessive-compulsive disorder (OCD). It has been proposed as an endophenotype for OCD because it is heritable and more prevalent in families of OCD patients. Consistent with this notion, it is also independent of symptom profile and symptom severity in cross-sectional studies. Longitudinally, it has been shown to be state independent in pediatric patients with OCD. The purpose of the present study was to investigate the state dependency of error monitoring by examining adult OCD patients before and after symptom reduction through cognitive-behavioral therapy (CBT). Method: Error-related and correct-related negativity as electrophysiological indicators of performance monitoring were recorded from 45 OCD patients and 39 healthy comparison subjects while performing a flanker task. Patients were assessed before starting and after completing a standard 30-session CBT, including exposure and response prevention, and healthy comparison subjects were tested after a comparable time interval. Results: Pretreatment, patients with OCD were characterized by enhanced error-related and correct-related negativity compared with healthy comparison subjects. This difference persisted after treatment when symptoms were substantially reduced. There was no significant correlation between symptom improvement and changes in performance monitoring and no difference in performance monitoring between treatment responders and nonresponders. Conclusions: This is the first longitudinal study in adult OCD patients showing stability of enhanced error monitoring following successful symptom reduction through CBT. It supports the hypothesis that overactive performance monitoring is an endophenotype that indicates vulnerability for OCD.
Gemcitabine Radiosensitization after High-Dose Samarium for Osteoblastic Osteosarcoma
Authors: Peter M. Anderson, Gregory A. Wiseman, Linda Erlandson, Vilmarie Rodriguez, Barbara Trotz, Stephen A. Dubansky, Karen Albritton
Journal: Clinical Cancer Research (2005)

Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose (153)Samarium ethylenediaminetetramethylenephosphonate (153Sm-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg 153Sm-EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of <3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after 153Sm to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m2) in combination with 153Sm-EDTMP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m2/d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed >1 year, there have been no durable responses. Thus, although high-dose 153Sm-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate.
Raised plasma concentration and ex vivo production of inflammatory chemokines in patients with systemic lupus erythematosus
Authors: L C W Lit
Journal: Annals of the Rheumatic Diseases (2005)

Chemokines are involved in leucocyte chemotaxis. Infiltrating leucocytes play an important role of tissue injury in systemic lupus erythematosus (SLE).To investigate the role of inflammatory chemokines and their association with interleukin 18 (IL18) in SLE pathogenesis and disease activity.Plasma concentrations and ex vivo peripheral blood mononuclear cell production of inflammatory chemokines IP-10, RANTES, MIG, MCP-1, TARC, IL8, and GROalpha, and proinflammatory cytokines IL18, IFNgamma, IL2, IL4, and IL10 were assayed in 80 SLE patients with or without renal disease and 40 healthy controls by immunofluorescence flow cytometry and enzyme linked immunosorbent assay.Plasma IP10, RANTES, MIG, MCP-1, GROalpha, and IL18 concentrations in all SLE patients were higher than in controls, and correlated significantly with SLEDAI score (all p<0.05). In SLE patients without renal disease, IP10, RANTES, MIG, MCP-1, IL8, and IL18 correlated positively with SLEDAI score, while in those with renal derangement, IP10, IL8, IL10, and IL18 correlated with disease activity (all p<0.05). Plasma IL18 concentration correlated positively with IP10, MIG, GROalpha, and IL8 in all SLE patients (all p<0.005). Mitogen induced increases in ex vivo production of IP10, MCP-1, TARC, IFNgamma, IL4, and IL10 were higher in all SLE patients regardless of their difference in disease activity (all p<0.05). Patients with renal disease had an augmented ex vivo release of RANTES.The correlation of raised plasma concentration and ex vivo production of inflammatory chemokines with disease activity, and their association with IL18, supports the view that chemotaxis of Th1/Th2 lymphocytes and neutrophils is important in SLE pathogenesis.
Dominant expression of type III hyperlipoproteinemia. Pathophysiological insights derived from the structural and kinetic characteristics of ApoE-1 (Lys146--&gt;Glu).
Authors: W A Mann, P Lohse, R E Gregg, R Ronan, J M Hoeg, L A Zech, H B Brewer
Journal: Journal of Clinical Investigation (1995)

Type III hyperlipoproteinemia is characterized by delayed chylomicron and VLDL remnant catabolism and is associated with homozygosity for the apoE-2 allele. We have identified a kindred in which heterozygosity for an apoE mutant, apoE-1 (Lys146-->Glu), is dominantly associated with the expression of type III hyperlipoproteinemia. DNA sequence analysis of the mutant apoE gene revealed a single-point mutation that resulted in the substitution of glutamic acid (GAG) for lysine (AAG) at residue 146 in the proposed receptor-binding domain of apoE. The pathophysiological effect of this mutation was investigated in vivo by kinetic studies in the patient and six normal subjects, and in vitro by binding studies of apoE-1 (Lys146-->Glu) to LDL receptors on human fibroblasts and to heparin. The kinetic studies revealed that apoE-1 (Lys146-->Glu) was catabolized significantly slower than apoE-3 in normals (P < 0.005). In the proband, the plasma residence times of both apoEs were substantially longer and the production rate of total apoE was about two times higher than in the control subjects. ApoE-1 (Lys146-->Glu) was defective in interacting with LDL receptors, and its ability to displace LDL in an in vitro assay was reduced to 7.7% compared with apoE-3. The affinity of apoE-1 (Lys146-->Glu) to heparin was also markedly reduced compared with both apoE-2 (Arg158-->Cys) and apoE-3. These abnormal in vitro binding characteristics and the altered in vivo metabolism of apoE-1 (Lys146-->Glu) are proposed to result in the functional dominance of this mutation in the affected kindred.
Prediction of Outcome in Bulimia Nervosa by Early Change in Treatment
Authors: Christopher G. Fairburn, W. Stewart Agras, B. Timothy Walsh, G. Terence Wilson, Eric Stice
Journal: American Journal of Psychiatry (2004)

The authors' goal was to identify predictors of treatment response in bulimia nervosa and, in particular, to attempt to replicate and extend the observation that early change predicts outcome.Predictors of response at the end of treatment and 8-month follow-up were sought from a group of 220 women treated with either cognitive behavior therapy or interpersonal psychotherapy.Early change in frequency of purging was the best predictor of response at the end of treatment and at 8-month follow-up.Early change in treatment is a robust and potent predictor of immediate and longer-term outcome in bulimia nervosa.
High prevalence of overuse injury among iron-distance triathletes
Authors: Christian A Andersen, Ben Clarsen, Tone V Johansen, Lars Engebretsen
Journal: British Journal of Sports Medicine (2013)

Background Triathlon is an increasingly popular sport at both the elite and the recreational level. However, there have been few high-quality studies of injuries and illnesses among triathletes. Objective To register overuse problems and acute injuries among iron-distance triathletes throughout a training season leading up to a major event. Methods A 26-week prospective cohort study was conducted including 174 participants of the 2011 Norseman Xtreme Triathlon. Data on overuse injuries located in the shoulder, lower back, thigh, knee and lower leg were collected every second week using the Oslo Sports Trauma Research Center Overuse Injury Questionnaire. Illnesses, acute injuries and overuse problems affecting other anatomical areas were also recorded using standard injury surveillance methods. Results The average prevalence of overuse problems was 56% (95% CI 51 to 61) (490 cases). The average prevalence of substantial overuse problems was 20% (95% CI 18 to 21) (165 cases). The most prevalent sites of overuse problems were the knee (25%), lower leg (23%) and lower back (23%). The acute injury incidence was 0.97 injuries per 1000 h of training (36 cases) and 1.02 injuries per 1000 h of competition (5 cases). A majority of moderate and severe acute injuries were located at the knee, shoulder/clavicle and sternum/ribs. The predominant types of acute injuries were contusions, fractures and sprains. The incidence of illness was 5.3/1000 athlete-days (156 cases). Conclusions Overuse problems constitute the majority of injury cases among iron-distance triathletes, and are far more common than acute injuries and illnesses. The most prevalent sites of injury in the present study were the knee, lower leg, lower back and shoulder. Future injury prevention studies in iron-distance triathletes should focus on these areas.
Systemic injection of a tripeptide inhibits the intracellular activation of CPP32-like proteases in vivo and fully protects mice against Fas-mediated fulminant liver destruction and death.
Authors: I Rodriguez, K Matsuura, C Ody, S Nagata, P Vassalli
Journal: The Journal of Experimental Medicine (1996)

Mice injected with anti-Fas antibody die within a few hours with total liver destruction due to massive apoptosis of hepatocytes. We show that this is preceded and accompanied by the sequential activation of cysteine proteases of the interleukin 1 beta-converting enzyme (ICE) and CPP32 types in the cytosol of the hepatocytes, and that proCPP32 cleavage and enzymatic activity can be prevented by intravenous injections of the tripeptide N-benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.fmk), an inhibitor of ICE-like proteases. Four Z-VAD.fmk injections at 1-hour intervals abolished all signs of liver damage after anti-Fas antibody injection and resulted in 100% long-range recovery, without residual tissue damage, from a condition otherwise uniformly fatal within &amp;lt; 3 hours. This treatment was effective even when delayed until some liver DNA degradation was already detectable. Injections of the tetrapeptide Ac-YVAD.cmk, more specific for the ICE-like subfamily of cysteine proteases but less cell permeable, also gave protection, but at higher doses and when injections started before that of anti-Fas antibody. These observations afford a way of temporarily modulating a number of apoptotic processes in vivo and may have important therapeutic implications in some human diseases.
Selective Cytotoxicity of Low-Density Lipoprotein to Helper T Cells of Cutaneous T-Cell Lymphoma After Photoperoxidation With 8-Methoxypsoralen
Authors: E. T. Fossel, J. G. Fletcher, J. McDonagh, K. K.S. Hui
Journal: JNCI Journal of the National Cancer Institute (1991)

Lymphocyte-containing plasma subjected to photolysis in the presence of 8-methoxypsoralen (methoxsalen, 8-MOP) has previously been shown to be effective against cutaneous T-cell lymphoma and the AIDS-related complex. The mechanism of this effect was thought to involve photoreaction of 8-MOP with DNA, based on certain in vitro experiments. The results of this study suggest a different mechanism. Low-density lipoprotein (LDL) from fresh human plasma was photosensitized by addition of 8-MOP and exposure to UV light (mp-LDL), and the reactions of the LDL lipids and the chemical actions induced by these reactions were monitored. In a separate procedure, LDL was peroxidized with hydrogen peroxide and peroxidase (p-LDL). mp-LDL and p-LDL were then tested in cytotoxicity assays on HuT-78 helper T cells of cutaneous T-cell lymphoma. These results indicate that (a) LDL in plasma in the presence of very low concentrations of 8-MOP (200 ng/mL) can be peroxidized by UV light; (b) this photoperoxidized LDL is cytotoxic to helper T cells of cutaneous T-cell lymphoma in a dose-dependent manner; but (c) it does not kill normal lymphocytes under similar conditions. The findings also suggest alternative therapeutic strategies for treatment of cutaneous T-cell lymphoma, such as direct utilization of peroxidized LDL.
Endothelin-1-, Endothelin-A-, and Endothelin-B-Receptor Expression Is Correlated with Vascular Endothelial Growth Factor Expression and Angiogenesis in Breast Cancer
Authors: Pia Wülfing, Christian Kersting, Joke Tio, Rudolph-Josef Fischer, Christian Wülfing, Christopher Poremba, Raihanatou Diallo, Werner Böcker, Ludwig Kiesel
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Endothelin-1 (ET-1) and its receptors (ETAR and ETBR), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas, and influence tumorigenesis and tumor progression by various mechanisms, including angiogenesis. The objective of the study was to clarify if expression of the ET axis participates in angiogenesis of breast carcinoma Experimental Design: We analyzed expression of ET-1, ETAR, ETBR, and vascular endothelial growth factor (VEGF) immunohistochemically in 600 tissue array specimens from 200 paraffin-embedded breast carcinomas performing tissue microarray technology. Microvessel density (MVD) was determined by counting microvessels (identified by factor VIII) in each core specimen. Results: Moderate or strong immunostaining was observed for ET-1 in 25.4%, for ETAR in 43.7%, and for ETBR in 22.2% of breast carcinomas. Of all cases, 44.7% showed significant expression of VEGF. MVD varied between different tumor specimens (range, 0–80; median, 17). We observed a statistically significant correlation between MVD and ET expression status with higher MVD in ET-positive tumors. Moreover, expression of VEGF was found more frequently in tumors with overexpression of the ET axis (each P &amp;lt; 0.001). Staining of VEGF was correlated positively with MVD Conclusions: These results indicate that increased ET-1, ETAR, and ETBR expression is associated with increased VEGF expression and higher vascularity of breast carcinomas and, thus, could be involved in the regulation of angiogenesis in breast cancer. Our findings provide evidence that the expression pattern of the ET-axis and in particular of ETAR may have clinical relevance in future antiangiogenic targeted therapies for breast cancer.