tbuckley/cabot-search huggingface dataset:
Negative Symptoms in Temporal Lobe Epilepsy
Authors: Kiesa Getz, Bruce Hermann, Michael Seidenberg, Brian Bell, Christian Dow, Jana Jones, Austin Woodard, Paul Rutecki, Raj Sheth, Dan O'Leary, Vince Magnotta
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: This study examined the frequency of negative and positive symptoms in nonpsychotic patients with temporal lobe epilepsy and the relationship of negative and positive symptoms to cognition, quantitative magnetic resonance imaging (MRI) volumetrics, and depression. METHOD: Eighty-four patients with temporal lobe epilepsy and 74 healthy comparison subjects were evaluated for negative and positive symptoms and underwent comprehensive neuropsychological evaluation, quantitative MRI volumetrics, and assessment of mood state and depression. RESULTS: Negative symptoms were significantly more prevalent in the patients with temporal lobe epilepsy (31%) than in the comparison subjects (8%). There was no difference between groups in the rate of positive symptoms. Although the epilepsy patients as a group exhibited generalized cognitive impairment relative to the comparison subjects, the epilepsy patients with negative symptoms performed significantly worse than patients without negative symptoms and comparison subjects across measures of nonverbal intelligence, visuoperception, speeded visuomotor processing, and memory. The epilepsy patients with negative symptoms exhibited significantly greater diffuse atrophy than the healthy comparison subjects and higher CSF volumes than the epilepsy patients without negative symptoms. The epilepsy patients with and without negative symptoms had statistically equivalent Beck Depression Inventory scores and lifetime history of mood disorders, including major depression. CONCLUSIONS: Negative but not positive symptoms were more prevalent in temporal lobe epilepsy patients than in healthy comparison subjects. Negative symptoms were independent of current and past depression and were associated with neuropsychological deficits exceeding the general cognitive morbidity associated with temporal lobe epilepsy and with quantitative MRI indices suggesting greater cerebral atrophy.
ErbB/HER receptor activation and preclinical efficacy of lapatinib in vestibular schwannoma
Authors: S. Ammoun, C. H. Cunliffe, J. C. Allen, L. Chiriboga, F. G. Giancotti, D. Zagzag, C. O. Hanemann, M. A. Karajannis
Journal: Neuro-Oncology (2010)

Vestibular schwannomas (VS) arising sporadically or in patients with neurofibromatosis type 2 (NF2) consistently lack expression of Merlin, a tumor suppressor. Conventional treatment options include surgery and radiotherapy but there is no validated medical option. Recent evidence suggests that Merlin deficiency may result in abnormal activation of receptor tyrosine kinases (RTKs) and downstream signaling, promoting tumor growth. Although small-molecule RTK inhibitors are widely available for clinical use, no such therapy has been validated in patients with VS. To screen for RTK activation, surgical VS specimens from patients with and without NF2 were analyzed by phospho-RTK profiling arrays. Downstream signaling pathway activation was analyzed by phospho-MAPK arrays. Activated RTKs and downstream kinases were validated immunohistochemically in corresponding formalin-fixed, paraffin-embedded tissues. Phospho-RTK arrays and immunohistochemistry showed consistent overexpression and activation of EGFR family receptors and evidence of ERK1/2 downstream signaling was observed in all samples analyzed (n = 11). Based on the findings, the small-molecule EGFR/ErbB2 kinase inhibitor lapatinib was selected for evaluation of target inhibition and treatment efficacy in our in vitro human schwannoma model. EGFR/ErbB2 targeted therapy with lapatinib inhibited ErbB2 phosphorylation and survivin upregulation, as well as downstream ERK1/2 and AKT activation, resulting in decreased proliferation. We conclude that EGFR family receptor activation is a consistent feature of both sporadic and NF2-related VS. Molecular targeted therapy with lapatinib downregulates survivin and has antiproliferative activity in a preclinical VS model. Based on these findings, a clinical trial with lapatinib for the treatment of VS is currently underway.
Passive Load and Angiotensin II Evoke Differential Responses of Gene Expression and Protein Synthesis in Cardiac Myocytes
Authors: Robert L. Kent, Paul J. McDermott
Journal: Circulation Research (1996)

Abstract This study introduced an improved model of loaded adult cardiocytes to address a proposed requirement for angiotensin II (Ang II) in the transduction pathway between load on the cardiac myocyte and its early anabolic responses of gene expression and acceleration of protein synthesis. The isolated cardiocytes were subjected to passive load by step increments of stretch and responded with proportional acceleration of protein synthesis in both adult and neonatal cardiocytes; this response was unaltered by 1 μmol/L [Sar 1 ,Ile 8 ]Ang II, an antagonist peptide to Ang II. Ang II from 1 nmol/L to 10 μmol/L did not increase protein synthesis after 4 hours in adult cardiocytes nor at 100 nmol/L in neonatal cardiocytes. However, 100 nmol/L Ang II did increase [ 3 H]phenylalanine incorporation into neonatal cardiocyte protein over a 24-hour period by 10%, whereas passive load increased [ 3 H]phenylalanine incorporation into protein by 30%, which was not blocked by [Sar 1 ,Ile 8 ]Ang II. Thus, the anabolic effect of load does not require Ang II to increase either 4-hour protein synthesis in both adult and neonatal cardiocytes or 24-hour [ 3 H]phenylalanine incorporation into protein in neonatal cardiocytes. The genetic response of the cardiocyte to load was examined by assessing c- fos and Na + -Ca 2+ exchanger mRNA levels, because these are rapidly expressed at the onset of cardiac pressure overload. The c- fos mRNA was increased fourfold within 1 hour after 100 nmol/L Ang II treatment of either adult or neonatal cardiocytes. This c- fos induction was blocked by [Sar 1 ,Ile 8 ]Ang II. One hour after loading of adult cardiocytes, induction of c- fos expression was increased threefold; this was also blocked by [Sar 1 ,Ile 8 ]Ang II. Thus, load-induced c- fos expression was Ang II dependent in adult cardiocytes. In contrast, exchanger mRNA levels were increased threefold 1 hour after loading of adult cardiocytes, but this increased expression was not blocked by [Sar 1 ,Ile 8 ]Ang II. For additional comparison, c- fos expression was induced by Ang II and phorbol myristate acetate, which did not induce exchanger expression; conversely, exchanger expression was induced by veratridine, which did not increase c- fos expression. Thus, separate c- fos and exchanger expression pathways can be differentiated in adult cardiocytes. This study demonstrated that Ang II is not required for load to initiate the anabolic processes of accelerated protein synthesis or enhanced Na + -Ca 2+ exchanger gene expression in cardiocytes; however, load induced c- fos expression is Ang II dependent.
Highly Expressed Genes in Rapidly Proliferating Tumor Cells as New Targets for Colorectal Cancer Treatment
Authors: Sarah Bazzocco, Higinio Dopeso, Fernando Carton-Garcia, Irati Macaya, Elena Andretta, Fiona Chionh, Paulo Rodrigues, Miriam Garrido, Hafid Alazzouzi, Rocio Nieto, Alex Sanchez, Simo Schwartz, Josipa Bilic, John M. Mariadason, Diego Arango
Journal: Clinical Cancer Research (2015)

The clinical management of colorectal cancer patients has significantly improved because of the identification of novel therapeutic targets such as EGFR and VEGF. Because rapid tumor proliferation is associated with poor patient prognosis, here we characterized the transcriptional signature of rapidly proliferating colorectal cancer cells in an attempt to identify novel candidate therapeutic targets.The doubling time of 52 colorectal cancer cell lines was determined and genome-wide expression profiling of a subset of these lines was assessed by microarray analysis. We then investigated the potential of genes highly expressed in cancer cells with faster growth as new therapeutic targets.Faster proliferation rates were associated with microsatellite instability and poorly differentiated histology. The expression of 1,290 genes was significantly correlated with the growth rates of colorectal cancer cells. These included genes involved in cell cycle, RNA processing/splicing, and protein transport. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and protoporphyrinogen oxidase (PPOX) were shown to have higher expression in faster growing cell lines and primary tumors. Pharmacologic or siRNA-based inhibition of GAPDH or PPOX reduced the growth of colon cancer cells in vitro. Moreover, using a mouse xenograft model, we show that treatment with the specific PPOX inhibitor acifluorfen significantly reduced the growth of three of the seven (42.8%) colon cancer lines investigated.We have characterized at the transcriptomic level the differences between colorectal cancer cells that vary in their growth rates, and identified novel candidate chemotherapeutic targets for the treatment of colorectal cancer.
Tumor Growth Inhibition and Potentiation of Immunotherapy by Indomethacin in Mice&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: N R Lynch, J C Salomon
Journal: JNCI Journal of the National Cancer Institute (1979)

Indomethacin was continuously administered in the drinking water of inbred C3H mice given grafts of syngeneic 3-methylcholanthrene-induced fibrosarcomas. A minor proportion of these animals died at the same time as the untreated controls, and others completely rejected their tumors; however, in most cases, the tumor growth rate was significantly slowed, and growth recommenced rapidly after drug withdrawal. This was the pattern for tumors either in their 10th to 14th transplant generation or only their third in vivo passage. Indomethacin exerted little prophylactic effect, in that it neither increased the minimal cell number required to initiate tumor growth nor significantly decreased the proportion of tumors established in drug-treated animals recieving tumor grafts. The injection of killed Corynebacterium parvum organisms into small, growing McC3-I tumors [intratumor (IT) route] caused the regression of most of these. In contrast, IT injection of BCG, ip injection of C. parvum, or IT injection of C. parvum into larger tumors had no effect. Oral administration of indomethacin enhanced BCG treatment and augmented the activity of C. parvum injected either systemically into animals with small tumors or IT into those with substantial tumor burdens. The duration of these effects was, however, often dependent on the continued administration of the drug.
Long Term Persistence of IgE Anti-Varicella Zoster (VZV) in Pediatric And Adult Serum Post Chicken Pox Infection and After Vaccination With Varicella Virus Vaccine
Authors: J JOSEKUTTY, H LEVTOV, K NOROWITZ, M NOWAKOWSKI, H DURKIN, T SMITHNOROWITZ, M BLUTH
Journal: Journal of Allergy and Clinical Immunology (2008)
A Candidate Gene Approach Identifies the TRAF1/C5 Region as a Risk Factor for Rheumatoid Arthritis
Authors: Fina A. S Kurreeman, Leonid Padyukov, Rute B Marques, Steven J Schrodi, Maria Seddighzadeh, Gerrie Stoeken-Rijsbergen, Annette H. M van der Helm-van Mil, Cornelia F Allaart, Willem Verduyn, Jeanine Houwing-Duistermaat, Lars Alfredsson, Ann B Begovich, Lars Klareskog, Tom W. J Huizinga, Rene E. M Toes
Journal: PLoS Medicine (2007)

Background Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting ∼1% of the population. The disease results from the interplay between an individual's genetic background and unknown environmental triggers. Although human leukocyte antigens (HLAs) account for ∼30% of the heritable risk, the identities of non-HLA genes explaining the remainder of the genetic component are largely unknown. Based on functional data in mice, we hypothesized that the immune-related genes complement component 5 (C5) and/or TNF receptor-associated factor 1 (TRAF1), located on Chromosome 9q33–34, would represent relevant candidate genes for RA. We therefore aimed to investigate whether this locus would play a role in RA. Methods and Findings We performed a multitiered case-control study using 40 single-nucleotide polymorphisms (SNPs) from the TRAF1 and C5 (TRAF1/C5) region in a set of 290 RA patients and 254 unaffected participants (controls) of Dutch origin. Stepwise replication of significant SNPs was performed in three independent sample sets from the Netherlands (ncases/controls = 454/270), Sweden (ncases/controls = 1,500/1,000) and US (ncases/controls = 475/475). We observed a significant association (p < 0.05) of SNPs located in a haplotype block that encompasses a 65 kb region including the 3′ end of C5 as well as TRAF1. A sliding window analysis revealed an association peak at an intergenic region located ∼10 kb from both C5 and TRAF1. This peak, defined by SNP14/rs10818488, was confirmed in a total of 2,719 RA patients and 1,999 controls (odds ratiocommon = 1.28, 95% confidence interval 1.17–1.39, pcombined = 1.40 × 10−8) with a population-attributable risk of 6.1%. The A (minor susceptibility) allele of this SNP also significantly correlates with increased disease progression as determined by radiographic damage over time in RA patients (p = 0.008). Conclusions Using a candidate-gene approach we have identified a novel genetic risk factor for RA. Our findings indicate that a polymorphism in the TRAF1/C5 region increases the susceptibility to and severity of RA, possibly by influencing the structure, function, and/or expression levels of TRAF1 and/or C5.
Molecular mechanisms of blood vessel growth
Authors: E Conway
Journal: Cardiovascular Research (2001)

The basic molecular mechanisms governing how endothelial cells, periendothelial cells and matrix molecules interact with each other and with numerous growth factors and receptors, to form blood vessels have been presented. The many insights gained from this basic knowledge are being extended to further understand pathological angiogenesis associated with disorders such as arterial stenosis, myocardial ischemia, atherosclerosis, allograft transplant stenosis. wound healing and tissue repair. As a result, novel angiogenic and anti-angiogenic molecules are rapid-ly entering the clinic, with the promise of relief from a host of medical disorders.
Endothelin-1–Induced Arrhythmogenic Ca <sup>2+</sup> Signaling Is Abolished in Atrial Myocytes of Inositol-1,4,5-Trisphosphate(IP <sub>3</sub> )–Receptor Type 2–Deficient Mice
Authors: Xiaodong Li, Aleksey V. Zima, Farah Sheikh, Lothar A. Blatter, Ju Chen
Journal: Circulation Research (2005)

Recent studies have suggested that inositol-1,4,5-trisphosphate-receptor (IP 3 R)–mediated Ca 2+ release plays an important role in the modulation of excitation–contraction coupling (ECC) in atrial tissue and the generation of arrhythmias, specifically chronic atrial fibrillation (AF). IP 3 R type-2 (IP 3 R2) is the predominant IP 3 R isoform expressed in atrial myocytes. To determine the role of IP 3 R2 in atrial arrhythmogenesis and ECC, we generated IP 3 R2-deficient mice. Our results revealed that endothelin-1 (ET-1) stimulation of wild-type (WT) atrial myocytes caused an increase in basal [Ca 2+ ] i , an enhancement of action potential (AP)-induced [Ca 2+ ] i transients, an improvement of the efficacy of ECC (increased fractional SR Ca 2+ release), and the occurrence of spontaneous arrhythmogenic Ca 2+ release events as the result of activation of IP 3 R-dependent Ca 2+ release. In contrast, ET-1 did not alter diastolic [Ca 2+ ] i or cause spontaneous Ca 2+ release events in IP 3 R2-deficient atrial myocytes. Under basal conditions the spatio-temporal properties (amplitude, rise-time, decay kinetics, and spatial spread) of [Ca 2+ ] i transients and fractional SR Ca 2+ release were not different in WT and IP 3 R2-deficient atrial myocytes. WT and IP 3 R2-deficient atrial myocytes also showed a significant and very similar increase in the amplitude of AP-dependent [Ca 2+ ] i transients and Ca 2+ spark frequency in response to isoproterenol stimulation, suggesting that both cell types maintained a strong inotropic reserve. No compensatory changes in Ca 2+ regulatory protein expression (IP 3 R1, IP 3 R3, RyR2, NCX, SERCA2) or morphology of the atria could be detected between WT and IP 3 R2-deficient mice. These results show that lack of IP 3 R2 abolishes the positive inotropic effect of neurohumoral stimulation with ET-1 and protects from its arrhythmogenic effects.
Effects of ranitidine and cisapride on acid reflux and oesophageal motility in patients with reflux oesophagitis: a 24 hour ambulatory combined pH and manometry study.
Authors: W Inauen, C Emde, B Weber, D Armstrong, H U Bettschen, T Huber, U Scheurer, A L Blum, F Halter, H S Merki
Journal: Gut (1993)

The effect of ranitidine and cisapride on acid reflux and oesophageal motility was investigated in 18 patients with endoscopically verified erosive reflux oesophagitis. Each patient was treated with placebo, ranitidine (150 mg twice daily), and ranitidine (150 mg twice daily) plus cisapride (20 mg twice daily) in a double blind, double dummy, within subject, three way cross over design. Oesophageal acidity and motility were monitored under ambulatory conditions for 24 hours on the fourth day of treatment, after a wash out period of 10 days during which patients received only antacids for relief of symptoms. Acid reflux was monitored by a pH electrode located 5 cm above the lower oesophageal sphincter. Intraoesophageal pressure was simultaneously recorded from four transducers placed 20, 15, 10, and 5 cm above the lower oesophageal sphincter. Upright reflux was three times higher than supine reflux (median (range) 13.3 (3.7-35.0)% v 3.7 (0-37.6)% of the time with pH &lt; 4.0, p &lt; 0.01, n = 18). Compared with placebo, ranitidine decreased total reflux (from 10.0 (3.2-32.6)% to 6.4 (1.2-22.9)%, p &lt; 0.01), upright reflux (p &lt; 0.05), supine reflux (p &lt; 0.001), and postprandial reflux (p &lt; 0.01), but did not affect oesophageal motility. The combination of ranitidine with cisapride further diminished the acid reflux found with ranitidine--that is, cisapride led to an additional reduction of total reflux (from 6.4 (1.2-22.9)% to 3.7 (1.0-12.7)%, p &lt; 0.01), supine reflux (p &lt; 0.05), and postprandial reflux (p &lt; 0.05). Cisapride also reduced both the number (p&lt;0.01) and duration (p&lt;0.05) of reflux episodes and significantly increased amplitude, duration, and propagation velocity of oesophageal contractions (p&lt;0.05) but did not affect the number of contractions. The findings show that the 30% reduction of oesophageal acid exposure achieved by a conventional dose of ranitidine (150 mg twice daily) can be improved to more than 60% by combination with cisapride (20 mg twice daily). The cisapride induced increase in oesophageal contractile force and propagation velocity seems to enhance the clearance of gastro-oesophageal reflux. Combination of a histamine H2 receptor antagonist with a prokinetic agent may therefore provide an alternative treatment for reflux oesophagitis.
What neuroimaging and perceptions of self-other similarity can tell us about the mechanism underlying mentalizing
Authors: Michael V. Lombardo, Bhismadev Chakrabarti, Simon Baron-Cohen
Journal: Behavioral and Brain Sciences (2009)

Abstract Carruthers' “mindreading is prior” model postulates one unitary mindreading mechanism working identically for self and other. While we agree about shared mindreading mechanisms, there is also evidence from neuroimaging and mentalizing about dissimilar others that suggest factors that differentially affect self-versus-other mentalizing. Such dissociations suggest greater complexity than the mindreading is prior model allows.
Interplay Between Heme Oxygenase-1 and the Multifunctional Transcription Factor Yin Yang 1 in the Inhibition of Intimal Hyperplasia
Authors: Konstanze Beck, Ben J. Wu, Jun Ni, Fernando S. Santiago, Kristine P. Malabanan, Cheng Li, Yutang Wang, Levon M. Khachigian, Roland Stocker
Journal: Circulation Research (2010)

induction of heme oxygenase (HO)-1 protects against experimental atherosclerotic diseases, and certain pharmacological HO-1 inducers, like probucol, inhibit the proliferation of vascular smooth muscle cells and, at the same time, promote the growth of endothelial cells in vivo and in vitro.because such cell-specific effects are reminiscent of the action of the transcription factor Yin Yang (YY)1, we tested the hypothesis that there is a functional relationship between HO-1 and YY1.we report that probucol increases the number of YY1(+) cells in rat carotid artery following balloon injury at a time coinciding with increased HO-1 expression. The drug also induces the expression of YY1 mRNA and protein in rat aortic smooth muscle cells (RASMCs) in vitro, as do other known HO-1 inducers (tert-butylhydroquinone and hemin) and overexpression of HO-1 using a human HMOX1 cDNA plasmid. Conversely, overexpression of YY1 induces expression of HO-1 in RASMCs. Induction of YY1 expression is dependent on HO-1 enzyme activity and its reaction product CO, because pharmacological inhibition of heme oxygenase activity or CO scavenging block, whereas exposure of RASMCs to a CO-releasing molecule increases, YY1 expression. Furthermore, RNA interference knockdown of YY1 prevents probucol or adeno-HO-1 from inhibiting RASMC proliferation in vitro and neointimal formation in vivo.our findings show, for the first time, that HO-1 functionally interplays with the multifunctional transcription factor YY1 and that this interplay explains some of the protective activities of HO-1.
Prevalence, Natural Course, and Risk Factors of Insomnia Comorbid With Cancer Over a 2-Month Period
Authors: Josée Savard, Julie Villa, Hans Ivers, Sébastien Simard, Charles M. Morin
Journal: Journal of Clinical Oncology (2009)

Purpose This study aimed to assess the prevalence, natural course, and risk factors of insomnia comorbid with cancer over a 2-month period. Patients and Methods All patients scheduled to receive a curative surgery for a first diagnosis of nonmetastatic cancer were approached to participate in the study on the day of their preoperative visit. As part of a larger population-based longitudinal study, 991 cancer patients completed various self-report scales and an insomnia diagnostic interview at the perioperative phase (T1) and 2 months later (T2). Results At T1, 28.5% of the patients met the diagnostic criteria for an insomnia syndrome, and 31.0% had insomnia symptoms; these rates decreased to 26.2% and 22.2%, respectively, at T2. The highest rates of insomnia were found in breast cancer patients, whereas the lowest rates were obtained in prostate cancer patients. Findings indicated an incidence rate of 18.6%, a persistence rate of 68.0%, and a remission rate of 32.0%. Female sex and the presence of an arousability trait (predisposing factors), a diagnosis of head and neck cancer, the administration of surgery, and an increase in anxiety symptoms between T1 and T2 (precipitating factors), and higher baseline levels and increases between T1 and T2 in dysfunctional beliefs about sleep, sleep monitoring, and maladaptive sleep behaviors (maintenance factors) were all associated with an increased risk for insomnia incidence. Conclusion This study confirms the high prevalence of insomnia comorbid with cancer during the 2 months after the perioperative visit and identifies several factors that might be involved in its development.