tbuckley/cabot-search huggingface dataset:
Cardiac Stem Cell Hybrids Enhance Myocardial Repair
Authors: Pearl Quijada, Hazel T. Salunga, Nirmala Hariharan, Jonathan D. Cubillo, Farid G. El-Sayed, Maryam Moshref, Kristin M. Bala, Jacqueline M. Emathinger, Andrea De La Torre, Lucia Ormachea, Roberto Alvarez, Natalie A. Gude, Mark A. Sussman
Journal: Circulation Research (2015)

Rationale: Dual cell transplantation of cardiac progenitor cells (CPCs) and mesenchymal stem cells (MSCs) after infarction improves myocardial repair and performance in large animal models relative to delivery of either cell population. Objective: To demonstrate that CardioChimeras (CCs) formed by fusion between CPCs and MSCs have enhanced reparative potential in a mouse model of myocardial infarction relative to individual stem cells or combined cell delivery. Methods and Results: Two distinct and clonally derived CCs, CC1 and CC2, were used for this study. CCs improved left ventricular anterior wall thickness at 4 weeks post injury, but only CC1 treatment preserved anterior wall thickness at 18 weeks. Ejection fraction was enhanced at 6 weeks in CCs, and functional improvements were maintained in CCs and CPC+MSC groups at 18 weeks. Infarct size was decreased in CCs, whereas CPC+MSC and CPC parent groups remained unchanged at 12 weeks. CCs exhibited increased persistence, engraftment, and expression of early commitment markers within the border zone relative to combinatorial and individual cell population–injected groups. CCs increased capillary density and preserved cardiomyocyte size in the infarcted regions suggesting CCs role in protective paracrine secretion. Conclusions: CCs merge the application of distinct cells into a single entity for cellular therapeutic intervention in the progression of heart failure. CCs are a novel cell therapy that improves on combinatorial cell approaches to support myocardial regeneration.
Identification of a common T/natural killer cell progenitor in human fetal thymus.
Authors: M J Sánchez, M O Muench, M G Roncarolo, L L Lanier, J H Phillips
Journal: The Journal of Experimental Medicine (1994)

The phenotypic similarities between natural killer (NK) and T cells have led to the hypothesis that these distinctive lymphocyte subsets may be developmentally related and thus may share a common progenitor (Lanier, L. L., H. Spits, and J. H. Phillips, 1992. Immunol. Today. 13:392; Rodewald, H.-R., P. Moingeon, J. L. Lurich, C. Dosiou, P. Lopez, and E. L. Reinherz. 1992. Cell. 69:139). In this report, we have investigated the potential of human CD34+ triple negative thymocytes ([TN] CD3-, CD4-, CD8-) to generate both T cells and NK cells in murine fetal thymic organ cultures (mFTOC) and in vitro clonogenic assays. CD34+ TN thymocytes, the majority of which express prominent cytoplasmic CD3 epsilon (cytoCD3 epsilon) protein, can be divided into high (CD34Bright) and low (CD34Dim) surface expressing populations. CD34Bright TN thymocytes were capable of differentiating into T and NK cells when transferred into mFTOC, and demonstrated high NK cell clonogenic capabilities when cultured in interleukin (IL)-2, IL-7, and stem cell factor (SCF). Likewise, CD34Bright TN thymocyte clones after 5 d in culture were capable of generating NK and T cells when transferred into mFTOC but demonstrated clonogenic NK cell differentiation capabilities when maintained in culture with IL-2. CD34Dim TN thymocytes, however, possessed only T cell differentiation capabilities in mFTOC but were not expandable in clonogenic conditions containing IL-2, IL-7, and SCF. No significant differentiation of other cell lineage was detected in either mFTOC or in clonogenic assays from CD34+ TN thymocytes. These results represent the first definitive evidence of a common T/NK cell progenitor in the human fetal thymus and delineate the point in thymocyte differentiation where T and NK cells diverge.
Cryptogenic organising pneumonia or acute fibrinous and organising pneumonia?
Authors: V. Poletti, G. L. Casoni
Journal: European Respiratory Journal (2005)

Cryptogenic organising pneumonia or acute fibrinous and organising pneumonia?To the Editors:In a recent issue of the European Respiratory Journal, CHEE et al.[1] present a case that was diagnosed and treated as cryptogenic organising pneumonia.We have a few comments about this case.
Use of HLA Typing in Diagnosing Celiac Disease in Patients With Type 1 Diabetes
Authors: Alessandra Doolan, Kim Donaghue, Jan Fairchild, Melanie Wong, Andrew J. Williams
Journal: Diabetes Care (2005)

OBJECTIVE—This study examines the use of HLA typing for the diagnosis of celiac disease in a group of Australians with type 1 diabetes. RESEARCH DESIGN AND METHODS—Subjects included 131 sequential patients with type 1 diabetes (mean age 17 years [range 10–37]), 77 patients with biopsy-proven celiac disease (mean age 52 years [range 12–84]), and 162 healthy control subjects (mean age 17 years [range 2 months to 56 years]). Subjects were prospectively screened for celiac disease using endomysial antibodies (EMAs), tissue transglutaminase antibodies (TTGAs), and celiac disease–specific HLA typing. RESULTS—Celiac disease was diagnosed in 11 subjects after an intestinal biopsy (prevalence 8.4%). There was 95% agreement between TTGA and EMA for positive results and 100% for negative results. There was no significant difference for HLA DQ2 and DR4 among patients with type 1 diabetes with or without celiac disease. CONCLUSIONS—The prevalence of celiac disease among patients with type 1 diabetes is higher than previously estimated in Australia. TTGA is a valuable diagnostic tool that can be used for screening celiac disease in patients with type 1 diabetes. HLA typing should not be used in the diagnosis of celiac disease in patients with type 1 diabetes because of the similarities of HLA types between patients with type 1 diabetes and those with celiac disease.
Species-specific shifts in centromere sequence composition are coincident with breakpoint reuse in karyotypically divergent lineages
Authors: Kira V Bulazel, Gianni C Ferreri, Mark DB Eldridge, Rachel J O'Neill
Journal: Genome biology (2007)

It has been hypothesized that rapid divergence in centromere sequences accompanies rapid karyotypic change during speciation. However, the reuse of breakpoints coincident with centromeres in the evolution of divergent karyotypes poses a potential paradox. In distantly related species where the same centromere breakpoints are used in the independent derivation of karyotypes, centromere-specific sequences may undergo convergent evolution rather than rapid sequence divergence. To determine whether centromere sequence composition follows the phylogenetic history of species evolution or patterns of convergent breakpoint reuse through chromosome evolution, we examined the phylogenetic trajectory of centromere sequences within a group of karyotypically diverse mammals, macropodine marsupials (wallabies, wallaroos and kangaroos). The evolution of three classes of centromere sequences across nine species within the genus Macropus (including Wallabia) were compared with the phylogenetic history of a mitochondrial gene, Cytochrome b (Cyt b), a nuclear gene, selenocysteine tRNA (TRSP), and the chromosomal histories of the syntenic blocks that define the different karyotype arrangements. Convergent contraction or expansion of predominant satellites is found to accompany specific karyotype rearrangements. The phylogenetic history of these centromere sequences includes the convergence of centromere composition in divergent species through convergent breakpoint reuse between syntenic blocks. These data support the 'library hypothesis' of centromere evolution within this genus as each species possesses all three satellites yet each species has experienced differential expansion and contraction of individual classes. Thus, we have identified a correlation between the evolution of centromere satellite sequences, the reuse of syntenic breakpoints, and karyotype convergence in the context of a gene-based phylogeny.
A phase I/II study of sepantronium bromide (YM155, survivin suppressor) with paclitaxel and carboplatin in patients with advanced non-small-cell lung cancer
Authors: R.J. Kelly, A. Thomas, A. Rajan, G. Chun, A. Lopez-Chavez, E. Szabo, S. Spencer, C.A. Carter, U. Guha, S. Khozin, S. Poondru, C. Van Sant, A. Keating, S.M. Steinberg, W. Figg, G. Giaccone
Journal: Annals of Oncology (2013)
Abstract 817: Myo10 is a Sensor for Endothelial Migration Induced by BMP6 via Regulation of Filopodia
Authors: Xinchun Pi, Rongqin Ren, Russell Kelley, Aparna Bhaskar, Richard Cheney, Winston C Patterson
Journal: Circulation (2006)

Endothelial cell migration is a key step during angiogenesis and dysregulation of this process is held responsible for many aspects of cardiovascular and other diseases. The bone morphogenetic proteins (BMP) are potent stimulators of cell migration and angiogenesis. However, the signaling pathways necessary for migration induced by BMPs are still poorly understood. To search for novel genes contributing to BMP-induced endothelial migration, we performed gene expression profiling experiments using microarray analysis technology. We found that Myosin X (Myo10), which is known to regulate filopodial integrity, is potently upregulated by BMP2 or BMP6. RT-PCR and western blotting analysis indicate more than 10-fold increase of Myo10 mRNA and protein levels. The upregulation of Myo10 is regulated through the Smad pathway since Smad inhibitors Smad6 and Smad7 significantly inhibit Myo10 upregulation induced by BMP6. In endothelial cells, BMP6-induced Myo10 localizes in filopodia and filopodia number increases from 20±11 to 54±17 per cell as determined by scanning electron microscopy. This finding is consistent with our observation that increased filopodial extensions are induced by overexpression of Myo10. Co-immunoprecipitation experiments demonstrates that endogenous Myo10 and BMP6 type I receptor ALK6 are associated and that BMP6 treatment increases their binding. Immunofluorescence data demonstrates that with BMP6 treatment ALK6 translocates into filopodia, co-localizes with Myo10 and undergoes intrafilopodia motility. Boyden chamber assays indicate that the knockdown of Myo10 with specific small hairpin- (sh−) RNAs inhibits BMP6-induced cell migration (from 53±5 to 4±2 cells per field), surporting the model that Myo10 located in filopodia plays a key role in endothelial migration induced by BMP6. However, overexpression of Myo10 alone is not sufficient to increase endothelial migration compared to control (from 4±1 to 7±1 cells per field), and that a BMP6 gradient is needed to increase cell migration significantly (from 7±1 to 29±5 cells per field). Therefore, our data strongly suggest that Myo10 plays a critical role as a sensor in the guidance of endothelial migration towards BMP6 gradient via the regulation of filopodia function.
Memory reconsolidation and psychotherapeutic process
Authors: Israel Liberzon, Arash Javanbakht
Journal: Behavioral and Brain Sciences (2015)

Abstract Lane et al. propose a heuristic model in which distinct, and seemingly irreconcilable, therapies can coexist. Authors postulate that memory reconsolidation is a key common neurobiological process mediating the therapeutic effects. This conceptualization raises a set of important questions regarding neuroscience and translational aspects of fear memory reconsolidation. We discuss the implications of the target article's memory reconsolidation model in the development of more effective interventions, and in the identification of less effective, or potentially harmful approaches, as well as concepts of contextualization, optimal arousal, and combined therapy
White Matter Alteration in Metabolic Syndrome
Authors: Keigo Shimoji, Osamu Abe, Takanori Uka, Hasina Yasmin, Koji Kamagata, Kouichi Asahi, Masaaki Hori, Atsushi Nakanishi, Yoshifumi Tamura, Hirotaka Watada, Ryuzo Kawamori, Shigeki Aoki
Journal: Diabetes Care (2012)

OBJECTIVE We explored the regional pattern of white matter alteration in subjects with metabolic syndrome. We also investigated whether white matter alteration was correlated with BMI. RESEARCH DESIGN AND METHODS Seven middle-aged men with metabolic syndrome and seven without metabolic syndrome underwent diffusion tensor imaging with a 3T magnetic resonance imaging imager. We analyzed the fractional anisotropy (FA) values by using a tract-based spatial statistics technique (whole-brain analysis). We subsequently focused on measuring the mean FA values of the right inferior fronto-occipital fasciculus (IFOF) of all subjects by tract-specific analysis (regional brain analysis). We used a Pearson correlation coefficient to evaluate the relationship between BMI and mean FA values of the right IFOF. RESULTS In the whole-brain analysis, subjects with metabolic syndrome had significantly lower FA values than control subjects in part of the right external capsule (part of the right IFOF), the entire corpus callosum, and part of the deep white matter of the right frontal lobe. In the regional brain analysis, the mean FA value of the right IFOF was 0.41 ± 0.03 for subjects with metabolic syndrome and 0.44 ± 0.05 for control subjects. A significant negative correlation was observed between BMI and FA values in the right IFOF (r = −0.56, P &amp;lt; 0.04). CONCLUSIONS Our results show that microstructural white matter changes occur in patients with metabolic syndrome. FA values may be useful indices of white matter alterations in patients with metabolic syndrome.
Risk of Pure Red Cell Aplasia in Patients With Hepatitis C Receiving Antiviral Therapy and an Erythropoiesis-Stimulating Agent
Authors: Jerome Rossert, Susan Yue, Karen Smirnakis, Daniel T. Mytych, Larry Johnson, Elias Kouchakji, Nicole Casadevall
Journal: Clinical Gastroenterology and Hepatology (2013)
Malnutrition at Age 3 Years and Externalizing Behavior Problems at Ages 8, 11, and 17 Years
Authors: Jianghong Liu, Adrian Raine, Peter H. Venables, Sarnoff A. Mednick
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Poor nutrition is thought to predispose to externalizing behavior problems, but to date there appear to have been no prospective longitudinal studies testing this hypothesis. This study assessed whether 1) poor nutrition at age 3 years predisposes to antisocial behavior at ages 8, 11, and 17 years, 2) such relationships are independent of psychosocial adversity, and 3) IQ mediates the relationship between nutrition and externalizing behavior problems. METHOD: The participants were drawn from a birth cohort (N=1,795) in whom signs of malnutrition were assessed at age 3 years, cognitive measures were assessed at ages 3 and 11 years, and antisocial, aggressive, and hyperactive behavior was assessed at ages 8, 11, and 17 years. RESULTS: In relation to comparison subjects (N=1,206), the children with malnutrition signs at age 3 years (N=353) were more aggressive or hyperactive at age 8 years, had more externalizing problems at age 11, and had greater conduct disorder and excessive motor activity at age 17. The results were independent of psychosocial adversity and were not moderated by gender. There was a dose-response relationship between degree of malnutrition and degree of externalizing behavior at ages 8 and 17. Low IQ mediated the link between malnutrition and externalizing behavior at ages 8 and 11. CONCLUSIONS: These results indicate that malnutrition predisposes to neurocognitive deficits, which in turn predispose to persistent externalizing behavior problems throughout childhood and adolescence. The findings suggest that reducing early malnutrition may help reduce later antisocial and aggressive behavior.
P215 Altering Practice in Mesothelioma–the Value of Specialist MDT Input: Abstract P215 Table 1.
Authors: M Murthy, N Hunt, G Jones, D Komrower, C Smyth, M Walshaw
Journal: Thorax (2013)

<h3>Introduction</h3> Mesothelioma is an uncommon malignancy with a poor prognosis, and in order to improve its management all cases within each cancer network should be discussed at a specialist MDT, which advises individual cancer units on the best treatment approach for their patients. The regional specialist mesothelioma MDT for the Mersey and Cheshire Cancer Network (MCCN) was incorporated in 2009, and we were interested to assess the effect this had on the outcome of mesothelioma patients attending our large cancer unit. <h3>Method</h3> We compared clinical parameters for all our mesothelioma patients before and after the inception of the specialist MDT, looking at symptoms, investigations carried out, the histological rate and type, and treatments offered. <h3>Results</h3> Fifty five patients were diagnosed between 2007 and 2011(mean age 75 years [SD 7.35], median WHO performance status 1, 46 male). Most (85%) were symptomatic at presentation–18 (32%) had chronic cough, 27 (49%) pain and 38 (69%) dyspnoea. 23 (42%) had documented asbestos exposure. Diagnosis was made clinically in 1 patient and by cytology alone in 4 patients. Diagnostic methodology and treatment modalities for the 2-year periods before (2007–8) and after (2010–11) the specialist MDT formation are given in the table (Table 1). There was no difference in histological rates (100% and 92% respectively) or cell types between the two periods. <h3>Conclusions</h3> In the second time period, our use of radical oncological treatment increased and at the same time extensive surgical treatment decreased, in keeping with current considered best practice. These changes in clinical practice coincided with discussion of these cases at the newly formed MCCN specialist mesothelioma MDT. This study emphasises the value of an expert multidisciplinary approach to the management of this unfortunate group of patients.
Mesenchymal Stromal Cell Mutations and Wound Healing Contribute to the Etiology of Desmoid Tumors
Authors: Adelaide M. Carothers, Hira Rizvi, Rian M. Hasson, Yvonne I. Heit, Jennifer S. Davids, Monica M. Bertagnolli, Nancy L. Cho
Journal: Cancer Research (2011)

Abstract Desmoid tumors are nonmalignant neoplasms of mesenchymal origin that mainly contain fibroblast lineage cells. These tumors often occur in patients with familial adenomatous polyposis (FAP) coli who have germ line mutations in the APC gene. Given emerging data that has implicated multipotent mesencyhmal stromal cells (MSC) in the origin of mesenchymal tumors, we hypothesized that desmoid tumors may arise in patients with FAP after MSCs acquire somatic mutations during the proliferative phase of wound healing. To test this idea, we examined 16 desmoid tumors from FAP-associated and sporadic cases, finding that all 16 of 16 tumors expressed stem cell markers, whereas matching normal stromal tissues were uniformly negative. Desmoid tumors also contained a subclass of fibrocytes linked to wound healing, angiogenesis, and fibrosis. Using an MSC cell line derived from an FAP-associated desmoid tumor, we confirmed an expected loss in the expression of adenomatous polyposis coli (APC) and the transcriptional repressor BMI-1 while documenting the coexpression of markers for chondrocytes, adipocytes, and osteocytes. Together, our findings argue that desmoid tumors result from the growth of MSCs in a wound healing setting that is associated with deregulated Wnt signaling due to APC loss. The differentiation potential of these MSCs combined with expression of BMI-1, a transcriptional repressor downstream of Hedgehog and Notch signaling, suggests that desmoid tumors may respond to therapies targeting these pathways. Cancer Res; 72(1); 346–55. ©2011 AACR.
Selective beta 1-adrenoceptor blockade enhances positive inotropic responses to endogenous catecholamines mediated through beta 2-adrenoceptors in human atrial myocardium.
Authors: J A Hall, A J Kaumann, M J Brown
Journal: Circulation Research (1990)

We determined the relative contribution of beta 1- and beta 2-adrenoceptor stimulation to the positive inotropic responses of human atrial myocardium to catecholamines. (-)Norepinephrine produced stimulation predominantly through beta 1-receptors and (-)epinephrine through both beta 1- and beta 2-receptors. However, there were marked differences in the responses of tissues from patients treated with the beta 1-selective antagonist atenolol compared with non-beta-blocker-treated patients; surprisingly, beta 2-mediated responses were enhanced, and beta 1-mediated responses were unaltered. There was an enhanced responsiveness to (-)epinephrine (atenolol treated: -log M EC50, 7.57 +/- 0.07; non-beta-blocker treated: -log M EC50, 6.77 +/- 0.17; p less than 0.001), and the relative importance of beta 2-adrenoceptor stimulation was increased for both (-)norepinephrine and (-)epinephrine. In tissues from atenolol-treated patients, salbutamol, a beta 2-selective partial agonist, had an enhanced potency and a greater intrinsic activity (atenolol treated: -log M EC50, 7.13 +/- 0.09; intrinsic activity, 0.86 +/- 0.04; non-beta-blocker treated: -log M EC50, 5.76 +/- 0.44; intrinsic activity, 0.39 +/- 0.13). We investigated possible mechanisms underlying the enhanced responsiveness to beta 2 stimulation. Determination of beta 2-adrenoceptor affinity for salbutamol showed no change of affinity in atenolol-treated patients. Responses of the tissues to the cyclic AMP analogue dibutyryl cyclic AMP were not different between atenolol-treated and non-beta-blocker-treated patients. The results suggest that chronic blockade of beta 1-adrenoceptors causes enhanced coupling of beta 2-adrenoceptors to adenylate cyclase or to other mechanisms leading to increased contractile force.
Angiotensin-Converting–Enzyme Inhibition in Stable Coronary Artery Disease
Authors: Eugene Braunwald, Michael J Domanski, Sarah E Fowler, Nancy L Geller, Bernard J Gersh, Judith Hsia, Marc A Pfeffer, Madeline M Rice, Yves D Rosenberg, Jean L Rouleau
Journal: New England Journal of Medicine (2004)

Angiotensin-converting-enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction, and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure.