tbuckley/cabot-search huggingface dataset:
Transcriptional Activation of the Zinc Finger Transcription Factor BTEB2 Gene by Egr-1 Through Mitogen-Activated Protein Kinase Pathways in Vascular Smooth Muscle Cells
Authors: Keiko Kawai-Kowase, Masahiko Kurabayashi, Yoichi Hoshino, Yoshio Ohyama, Ryozo Nagai
Journal: Circulation Research (1999)

We have recently demonstrated that a developmentally regulated zinc finger protein, basic transcription regulatory element binding protein 2 (BTEB2), is induced in neointimal smooth muscle in response to vascular injury. In this study, we investigated the molecular mechanisms regulating BTEB2 expression in vascular smooth muscle cells (SMCs) in vitro. BTEB2 mRNA expression is rapidly and persistently induced in SMCs by phorbol 12-myristate 13-acetate (PMA) and basic fibroblast growth factor. We have isolated and characterized the promoter region of the human BTEB2 gene to determine the regulatory network controlling expression of this gene in vascular SMCs. Functional studies on the BTEB2 promoter coupled to a luciferase reporter gene demonstrated activation of the promoter by PMA and basic fibroblast growth factor. Both characterization of DNA-protein complexes in vitro and site-specific mutation analysis of the BTEB2 promoter have defined a 9-bp sequence, 5'-CGCCCGCGC-3', located at -25, as the Egr-1 binding site mediating an induction of the BTEB2 promoter activity by PMA. In addition, we show that this site mediates inducible expression through the mitogen-activated protein kinase pathways. These results indicate that BTEB2 is a target of the early-response gene Egr-1, and mitogen-activated protein kinase pathways directly or indirectly activate BTEB2 expression. Given a rapid induction of Egr-1 on stimulation with growth factors or injury, these findings may represent at least one of the molecular mechanisms underlying phenotypic modulation of smooth muscles after vascular injury.
Bile salts and cholesterol in the pathogenesis of target cells in obstructive jaundice
Authors: Richard A. Cooper, James H. Jandl
Journal: Journal of Clinical Investigation (1968)

Free cholesterol is in rapid equilibrium between serum lipoproteins and red cells. The level of red cell cholesterol is influenced by bile salts, which shift the serum/cell partition of free cholesterol to the cell phase and which inhibit the cholesterol-esterifying mechanism. During incubation in normal serum possessing an active cholesterol-esterifying mechanism, red cells lose cholesterol and surface area and thereby become more spheroidal and less resistant to osmotic lysis. When exposed to serum from patients with obstructive jaundice or to normal serum with added bile salts, red cells accumulate cholesterol and increase their surface area, thereby acquiring a flattened shape and an increased resistance to osmotic lysis. The described gains and losses of red cell cholesterol and surface area do not involve metabolic injury and occur with no significant change in phospholipid content. The red cells of patients with obstructive jaundice are flat and osmotically resistant and have an increased cholesterol:phospholipid ratio. When transfused into normal subjects these "target cells" rapidly lose their osmotic resistance. Similarly, normal cells acquire osmotic resistance in the circulation of patients with obstructive jaundice. These reversible changes in shape occur with half-times of about 9 and 24 hr, respectively, and occur without impairing cell viability. These studies indicate that the red cell membrane accumulates cholesterol in obstructive jaundice as a consequence of the elevated levels of bile salts. The resulting increment in red cell surface area is responsible for the physical properties and appearance of target cells. These observations substantiate Murphy's findings in vitro indicating that cholesterol is an important determinant of red cell shape and that its content in the cell membrane may vary independently from the phospholipids. Presumably any process or disorder affecting cholesterol exchange in vivo is capable of critically modifying the shape and behavior of red cells.
O-acetylation of G<scp>d</scp>3
Authors: Helen Y. Chen, Ajit Varki
Journal: The Journal of Experimental Medicine (2002)

Glycosphingolipids (GSLs) are amphipathic molecules with a polar glycan chain as a head group and a hydrophobic sphingosine-containing ceramide tail, which is typically embedded in the outer leaflet of the plasma membrane ([1][1]). GSLs are no longer thought to be mere physical components of the
Association between HLA class II alleles and protection from or susceptibility to chronic hepatitis C
Authors: Claudio Zavaglia, Miryam Martinetti, Enrico Silini, Riccardo Bottelli, Cristina Daielli, Margherita Asti, Aldo Airoldi, Laura Salvaneschi, Mario U. Mondelli, Gaetano Ideo
Journal: Journal of Hepatology (1998)
Zeroing In on Early Cognitive Development in Schizophrenia
Authors: Dwight Dickinson
Journal: American Journal of Psychiatry (2014)

Thoughts about the role of development in schizophrenia have evolved in recent decades.Early formulations of the "neurodevelopmental hypothesis" suggested mechanisms whereby "probably congenital and static" neurophysiological insults might remain for the most part silent, behaviorally, until the onset of schizophrenia in late adolescence or early adulthood (1).Recent versions reflect a more dynamic view of the densely interacting effects of biology and environment on behavior over the course of development (2).They also emphasize the now extensive evidence that some children who will later have schizophrenia show marked abnormalities in motor, cognitive, emotional, and social development years before the onset of psychotic symptoms (3).Among these developmental manifestations, an increasing lagin intellectual development during childhood may show some specificity in prediction of later psychosis (4), while motor, emotional, and social problems seem to be nonspecific risk factors for a variety of adult neuropsychiatric outcomes (3).
OC-127 One thousand laparoscopic ROUX-EN-Y gastric bypasses: perioperative and long term outcomes
Authors: J C Tham, D Pournaras, I Finlay, D Titcomb, J Edmond, D Mahon, R Welbourn
Journal: Gut (2012)

<h3>Introduction</h3> Laparoscopic Roux-en-y gastric bypass (LRYGB) has been established as an effective treatment for obesity and obesity related morbidity. However, safety of LRYGB remains under public scrutiny. Defining operative outcomes is vital to establish its safety and long term efficacy. <h3>Methods</h3> One thousand consecutive patients underwent LRYGB as a primary procedure by two surgeons in a single centre from 2004 to 2011. Twenty-six patients had intra-gastric balloon insertion before LRYGB to reduce Body Mass Index (BMI). LRYGB was done using a retrocolic, antegastric linear staple technique with routine closure of internal hernia defects. Patient demographics and complications were collected prospectively in a local database, and after January 2009, in the National Bariatric Surgery Registry. The Obesity Surgery Mortality Risk Score (OS-MRS) was used for risk stratification. Analysis was performed on each 100 patients making up 10 groups sequentially with the first 100 in group 1. <h3>Results</h3> Mean age±SD was 45.5±10.4 with mean BMI of 49.5±7.7 and 79.3% were female. There were 61 (6.1%) high-risk patients (OS-MRS class C). The follow-up rate up to 6 years was 87.9%. There were four conversions-to-open surgery in the first 400 patients with no conversions thereafter. Mean % excess weight loss (EWL) pre-operatively as compared to initial weight was 11.6%±12.5. % EWL subsequently was: 1 year 67.7%±18.9; 2 years: 71.6%±20.3; 5 years: 57.5%±21.8; 6 years: 61.1%±21.4. Overall, the 30-day complication rate was 5.5% with a 30-day reoperation rate of 2.9%. The 30-day complication rate fell over time; 13 patients had a complication in group 1 compared to 1 patient in group 10 (p=0.03). Further, there was significant reduction in complications between groups 1 and 2 (p&lt;0.001) but no difference between each group thereafter. Major complications within 30 days postoperatively were gastrointestinal leak (0.6%), gastro-jejunal stenosis (0.3%), stenosis at the mesocolic defect (0.3%), jejuno-jejunostomy hernia (0.7%), mesocolic hernia (1%) and bleeding (2.1%). There was one death (0.1%) within the 30 postoperative days (in group 2). The cumulative complication rate at 6 years was 9.1% with 5.8% needing re-operation or endoscopic intervention. The mean operative time per group for the first 600 patients was, in minutes, 163±53.7, 129.2±109.8, 100.0±27.8, 104.3±28.9, 92.7±32.1 and 93.8±30.9, a significant decrease between groups 1 and 2 (p=0.003), 2 and 3 (p=0.007), and 4 and 5 (p=0.008) respectively, but not between 3 and 4. <h3>Conclusion</h3> LRYGB is a safe and efficacious procedure with sustained weight loss at 6 years. The learning curve is about 100 cases but operative time continues to improve up to the 500th case. A high volume centre is associated with low morbidity and mortality. <h3>Competing interests</h3> None declared.
Origins of Shared Genetic Variation in African Cichlids
Authors: Yong-Hwee E. Loh, Etienne Bezault, Frauke M. Muenzel, Reade B. Roberts, Ross Swofford, Marta Barluenga, Celeste E. Kidd, Aimee E. Howe, Federica Di Palma, Kerstin Lindblad-Toh, Jody Hey, Ole Seehausen, Walter Salzburger, Thomas D. Kocher, J. Todd Streelman
Journal: Molecular Biology and Evolution (2012)

Cichlid fishes have evolved tremendous morphological and behavioral diversity in the waters of East Africa. Within each of the Great Lakes Tanganyika, Malawi, and Victoria, the phenomena of hybridization and retention of ancestral polymorphism explain allele sharing across species. Here, we explore the sharing of single nucleotide polymorphisms (SNPs) between the major East African cichlid assemblages. A set of approximately 200 genic and nongenic SNPs was ascertained in five Lake Malawi species and genotyped in a diverse collection of ∼160 species from across Africa. We observed segregating polymorphism outside of the Malawi lineage for more than 50% of these loci; this holds similarly for genic versus nongenic SNPs, as well as for SNPs at putative CpG versus non-CpG sites. Bayesian and principal component analyses of genetic structure in the data demonstrate that the Lake Malawi endemic flock is not monophyletic and that river species have likely contributed significantly to Malawi genomes. Coalescent simulations support the hypothesis that river cichlids have transported polymorphism between lake assemblages. We observed strong genetic differentiation between Malawi lineages for approximately 8% of loci, with contributions from both genic and nongenic SNPs. Notably, more than half of these outlier loci between Malawi groups are polymorphic outside of the lake. Cichlid fishes have evolved diversity in Lake Malawi as new mutations combined with standing genetic variation shared across East Africa.
Hypoxia Alters the Sensitivity of the L-Type Ca <sup>2+</sup> Channel to α-Adrenergic Receptor Stimulation in the Presence of β-Adrenergic Receptor Stimulation
Authors: Livia C. Hool
Journal: Circulation Research (2001)

Abstract —The effects of α-adrenergic receptor (α-AR) stimulation alone and the effects in the presence of β-adrenergic receptor (β-AR) stimulation were examined on L-type Ca 2+ currents ( I Ca-L ) in the absence and presence of hypoxia. The α-AR agonist methoxamine either had no effect or had a slight inhibitory effect on basal I Ca-L in the absence and presence of hypoxia. Hypoxia significantly decreased the K 0.5 for activation of I Ca-L by norepinephrine from 79.8±6.6 to 13.3±0.7 nmol/L. To determine whether hypoxia specifically altered the sensitivity of the channel to α-AR stimulation, cells were exposed to increasing concentrations of methoxamine in the presence of 100 nmol/L isoproterenol (Iso). In the absence of hypoxia, methoxamine inhibited the Iso-activated I Ca-L in a concentration-dependent manner with an EC 50 of 86.9±9.9 μmol/L. However, in the presence of hypoxia, the EC 50 for inhibition of I Ca-L by methoxamine was significantly increased to 266.7±10.8 μmol/L. Methoxamine had little effect on I Ca-L activated by forskolin or histamine in the absence or presence of hypoxia. In addition, inhibition of protein kinase C by bisindolylmaleimide 1 or protein kinase C β peptide inhibitor had no effect on the methoxamine-induced antagonism of I Ca-L in the absence or presence of hypoxia. The tyrosine kinase inhibitor genistein attenuated the methoxamine response in nonhypoxic cells only. However, during hypoxia it was attenuated with the phospholipase A 2 inhibitors mepacrine and indomethacin. These findings represent a novel regulation of the L-type Ca 2+ channel by the phospholipase A 2 pathway and illustrate the complexity of regulation of the channel under hypoxic conditions.
HDAC5 and HDAC9 in Medulloblastoma: Novel Markers for Risk Stratification and Role in Tumor Cell Growth
Authors: Till Milde, Ina Oehme, Andrey Korshunov, Annette Kopp-Schneider, Marc Remke, Paul Northcott, Hedwig E. Deubzer, Marco Lodrini, Michael D. Taylor, Andreas von Deimling, Stefan Pfister, Olaf Witt
Journal: Clinical Cancer Research (2010)

Medulloblastomas are the most common malignant brain tumors in childhood. Survivors suffer from high morbidity because of therapy-related side effects. Thus, therapies targeting tumors in a specific manner with small molecules such as histone deacetylase (HDAC) inhibitors are urgently warranted. This study investigated the expression levels of individual human HDAC family members in primary medulloblastoma samples, their potential as risk stratification markers, and their roles in tumor cell growth.Gene expression arrays were used to screen for HDAC1 through HDAC11. Using quantitative real time reverse transcriptase-PCR and immunohistochemistry, we studied the expression of HDAC5 and HDAC9 in primary medulloblastoma samples. In addition, we conducted functional studies using siRNA-mediated knockdown of HDAC5 and HDAC9 in medulloblastoma cells.HDAC5 and HDAC9 showed the highest expression in prognostically poor subgroups. This finding was validated in an independent set of medulloblastoma samples. High HDAC5 and HDAC9 expression was significantly associated with poor overall survival, with high HDAC5 and HDAC9 expression posing an independent risk factor. Immunohistochemistry revealed a strong expression of HDAC5 and HDAC9 proteins in most of all primary medulloblastomas investigated. siRNA-mediated knockdown of HDAC5 or HDAC9 in medulloblastoma cells resulted in decreased cell growth and cell viability.HDAC5 and HDAC9 are significantly upregulated in high-risk medulloblastoma in comparison with low-risk medulloblastoma, and their expression is associated with poor survival. Thus, HDAC5 and HDAC9 may be valuable markers for risk stratification. Because our functional studies point toward a role in medulloblastoma cell growth, HDAC5 and HDAC9 may potentially be novel drug targets.
Even insured Americans are paying more for health care, studies show
Authors: J. Hopkins Tanne
Journal: BMJ (2009)

Several studies show that even US residents with health insurance are spending a higher proportion of their incomes on health care than ever before, and many women are ignoring health care because of costs.

The studies are published at a time when the new Obama administration is promoting healthcare reform and universal coverage as its most important goals.

A study by FamiliesUSA, a non-profit making organisation, found that 64 million people younger than 65 lived in families that spent more than 10% of their pre-tax income on health care—nearly one in four US residents younger than 65. Almost all of them (94%) had health …
Fluoxetine Versus Placebo in Preventing Relapse of Major Depression in Children and Adolescents
Authors: Graham J. Emslie, Beth D. Kennard, Taryn L. Mayes, Jeanne Nightingale-Teresi, Thomas Carmody, Carroll W. Hughes, A. John Rush, Rongrong Tao, Jeanne W. Rintelmann
Journal: American Journal of Psychiatry (2008)

The authors compared fluoxetine and placebo in continuation treatment to prevent relapse of major depressive disorder in children and adolescents.After a detailed evaluation, children and adolescents 7-18 years of age with major depressive disorder were treated openly with fluoxetine. Those who had an adequate response after 12 weeks, as indicated by a Clinical Global Impression improvement score of 1 or 2 and a decrease of at least 50% in Children's Depression Rating Scale-Revised score, were randomly assigned to receive fluoxetine or placebo for an additional 6 months. The primary outcome measures were relapse and time to relapse. Relapse was defined as either a score of 40 or higher on the Children's Depression Rating Scale with a history of 2 weeks of clinical deterioration, or clinical deterioration as judged by the clinician. Additional analyses were conducted with relapse defined only as a score of 40 or higher on the Children's Depression Rating Scale.Of 168 participants enrolled in acute fluoxetine treatment, 102 were randomly assigned to continuation treatment with fluoxetine (N=50) or placebo (N=52). Of these, 21 participants (42.0%) in the fluoxetine group relapsed, compared with 36 (69.2%) in the placebo group, a significant difference. Similarly, under the stricter definition of relapse, fewer participants in the fluoxetine group relapsed (N=11; 22.0%) than in the placebo group (N=25; 48.1%). Time to relapse was significantly shorter in the placebo group.Continuation treatment with fluoxetine was superior to placebo in preventing relapse and in increasing time to relapse in children and adolescents with major depression.
Toward Understanding the Functional Relevance of White Matter Deficits in Bipolar Disorder
Authors: Kathryn R. Cullen, Kelvin O. Lim
Journal: JAMA Psychiatry (2014)

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Sequencing the genome of the Atlantic salmon (Salmo salar)
Authors: William S Davidson, Ben F Koop, Steven JM Jones, Patricia Iturra, Rodrigo Vidal, Alejandro Maass, Inge Jonassen, Sigbjorn Lien, Stig W Omholt
Journal: Genome biology (2010)

The International Collaboration to Sequence the Atlantic Salmon Genome (ICSASG) will produce a genome sequence that identifies and physically maps all genes in the Atlantic salmon genome and acts as a reference sequence for other salmonids.
Effect of distal splenorenal shunt on survival of patients with primary biliary cirrhosis
Authors: Thomas D. Boyer, Dennis D. Kokenes, Gary Hertzler, Michael H. Kutner, Michael J. Henderson
Journal: Hepatology (1994)

Distal splenorenal shunt is known to effectively control bleeding from esophageal and gastric varices; however, the effect of this selective shunt on liver function is less well understood. We examined retrospectively the effect of distal splenorenal shunt on the survival of 19 patients with primary biliary cirrhosis subjected to surgery for bleeding varices over a 20-yr period and had been followed for at least 1 yr. Actual Kaplan-Meier survival curve was compared with predicted survival curve based on the Mayo Clinic model using clinical data collected at the time of surgery. The patients median length of follow-up was 65.9 mo. Ten of the 19 patients died or underwent orthotopic liver transplantation during the period of observation. The actual Kaplan-Meier and predicted Mayo Clinic model survival curves were similar and did not differ significantly. Survival was best in patients with good liver function (i.e., low Mayo risk scores). Distal splenorenal shunt, therefore, did not appear to have an adverse effect on the survival of patients with primary biliary cirrhosis. We conclude that variceal bleeding in primary biliary cirrhosis patients with good liver function should not be considered an indication for liver transplantation. Instead, if treatment with sclerotherapy or beta-blockers fails then distal splenorenal shunt will prevent recurrent bleeding in 90% of patients and leave them with an excellent prognosis.
Severe Mood Dysregulation, Irritability, and the Diagnostic Boundaries of Bipolar Disorder in Youths
Authors: Ellen Leibenluft
Journal: American Journal of Psychiatry (2010)

In recent years, increasing numbers of children have been diagnosed with bipolar disorder. In some cases, children with unstable mood clearly meet current diagnostic criteria for bipolar disorder, and in others, the diagnosis is unclear. Severe mood dysregulation is a syndrome defined to capture the symptomatology of children whose diagnostic status with respect to bipolar disorder is uncertain, that is, those who have severe, nonepisodic irritability and the hyperarousal symptoms characteristic of mania but who lack the well-demarcated periods of elevated or irritable mood characteristic of bipolar disorder. Levels of impairment are comparable between youths with bipolar disorder and those with severe mood dysregulation. An emerging literature compares children with severe mood dysregulation and those with bipolar disorder in longitudinal course, family history, and pathophysiology. Longitudinal data in both clinical and community samples indicate that nonepisodic irritability in youths is common and is associated with an elevated risk for anxiety and unipolar depressive disorders, but not bipolar disorder, in adulthood. Data also suggest that youths with severe mood dysregulation have lower familial rates of bipolar disorder than do those with bipolar disorder. While youths in both patient groups have deficits in face emotion labeling and experience more frustration than do normally developing children, the brain mechanisms mediating these pathophysiologic abnormalities appear to differ between the two patient groups. No specific treatment for severe mood dysregulation currently exists, but verification of its identity as a syndrome distinct from bipolar disorder by further research should include treatment trials.