tbuckley/cabot-search huggingface dataset:
ERBB2 Induces an Antiapoptotic Expression Pattern of Bcl-2 Family Members in Node-Negative Breast Cancer
Authors: Ilka Brigitte Petry, Esther Fieber, Marcus Schmidt, Mathias Gehrmann, Susanne Gebhard, Matthias Hermes, Wiebke Schormann, Silvia Selinski, Evgenia Freis, Holger Schwender, Marc Brulport, Katja Ickstadt, Jörg Rahnenführer, Lindsey Maccoux, Jonathan West, Heinz Kölbl, Martin Schuler, Jan Georg Hengstler
Journal: Clinical Cancer Research (2010)

Members of the Bcl-2 family act as master regulators of mitochondrial homeostasis and apoptosis. We analyzed whether ERBB2 influences the prognosis of breast cancer by influencing the proapoptotic versus antiapoptotic balance of Bcl-2 family members.ERBB2-regulated Bcl-2 family members were identified by inducible expression of ERBB2 in MCF-7 breast cancer cells and by correlation analysis with ERBB2 expression in breast carcinomas. The prognostic relevance of ERBB2-regulated and all additional Bcl-2 family members was determined in 782 patients with untreated node-negative breast cancer. The biological relevance of ERBB2-induced inhibition of apoptosis was validated in a murine tumor model allowing conditional ERBB2 expression.ERBB2 caused an antiapoptotic phenotype by upregulation of MCL-1, TEGT, BAG1, BNIP1, and BECN1 as well as downregulation of BAX, BMF, BNIPL, CLU, and BCL2L13. Upregulation of the antiapoptotic MCL-1 [P = 0.001, hazard ratio (HR) 1.5] and BNIP3 (P = 0.024; HR, 1.4) was associated with worse prognosis considering metastasis-free interval, whereas clusterin (P = 0.008; HR, 0.88) and the proapoptotic BCL2L13 (P = 0.019; HR, 0.45) were associated with better prognosis. This indicates that ERBB2 alters the expression of Bcl-2 family members in a way that leads to adverse prognosis. Analysis of apoptosis and tumor remission in a murine tumor model confirmed that the prototypic Bcl-2 family member Bcl-x(L) could partially substitute for ERBB2 to antagonize tumor remission.Our results support the concept that ERBB2 influences the expression of Bcl-2 family members to induce an antiapoptotic phenotype. Antagonization of antiapoptotic Bcl-2 family members might improve breast cancer therapy, whereby MCL-1 and BNIP3 represent promising targets.
Cardiomyocyte apoptosis in hypertensive cardiomyopathy
Authors: A GONZALEZ
Journal: Cardiovascular Research (2003)

It is widely accepted that there are two principal forms of cell death; namely, necrosis and apoptosis. According to the classical view, necrosis is the major mechanism of cardiomyocyte death in cardiac diseases. However, in the past few years observations have been made showing that cardiomyocyte apoptosis occurs in diverse conditions and that apoptosis may be a contributing cause of the loss and functional abnormalities of cardiomyocytes with important pathophysiological consequences. In this regard, although a number of formal proofs are pending, it is conceivable that cardiomyocyte apoptosis may be an important variable in the clinical evolution of hypertensive cardiomyopathy. This review summarizes recent evidence demonstrating that cardiomyocyte apoptosis is abnormally stimulated in the heart of animals and humans with arterial hypertension. In addition, the potential mechanisms of cardiomyocyte apoptosis in hypertension and its detrimental impact on cardiac function will be addressed. Finally, the perspectives of strategies aimed to detect and modulate apoptosis of cardiomyocytes in hypertensive cardiomyopathy will be considered.
Different vulnerabilities for addiction may contribute to the same phenomena and some additional interactions
Authors: Andrew James Goudie, Matt Field, Jon Cole
Journal: Behavioral and Brain Sciences (2008)

Abstract The framework for addiction offered by the target article can perhaps be simplified into fewer, more basic, vulnerabilities. “Impulsivity” covers a number of vulnerabilities, not just enhanced delay discounting. Real-world drug-use decisions involve both delay and probability discounting. The motivational salience of, and attentional bias for, drug cues may be related to a number of vulnerabilities. Interactions among vulnerabilities are of significance and complicate the application of this framework.
A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease
Authors: David K. Wood, Alicia Soriano, L. Mahadevan, John M. Higgins, Sangeeta N. Bhatia
Journal: Science Translational Medicine (2012)

Sickle cell patients are stratified according to risk of vaso-occlusion on the basis of the dynamic biophysical properties of their blood as measured ex vivo in a microfluidic system.
Potential molecular markers and therapeutic targets of endometrial cancer in Hong Kong women
Authors: Y.F. Wong, T.H. Cheung, S.F. Yim, T.K.H. Chung
Journal: Clinical Cancer Research (2008)

B17   Endometrial cancer is one of the commonest malignancies in Hong Kong women. About 80-90 % of the endometrial cancer are endometrioid endometrial adenocarcinomas (EEC). MicroRNAs (miRNAs) are small non-coding RNAs which are recently found to be able to regulate the function of target genes by inducing cleavage of the targeted messenger or by inhibiting translation. miRNAs shown to be up- or down-regulated in cancers may be used as molecular tumor markers, while correlation between the expression of miRNAs and their effects on tumor-related genes, tumorigenesis and the proliferation of cancer cells may implicate potential of miRNA as therapeutic targets to treatment cancers. The present study, a parallel to global gene expression profiling, was to identify dysregulated miRNAs associated with EEC, and further to determine their correlation with clinico-pathological characteristics and identify predicted target genes of the dysregulated miRNAs. Using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), profiling of miRNA expression was performed in 30 EECs and 22 normal counterparts in which genome-wide gene expression had been profiled before. Clustering analysis identified 30 miRNAs which were significantly dysregulated in EEC. The expression of a sub-group of miRNAs was significantly correlated with clinico-pathological characteristics including stage, myometrium invasion, recurrence and lymph node involvement. By searching for predicted miRNA targets (http://www.diana.pcbi.upenn.edu/cgibin/miRGen/v3/Targets.cgi) that were linked to the dysregulated genes previously revealed in global gene expression profiling of these EECs, 68 genes were predicted as the candidate targets of these 30 dysregulated miRNAs. miR-205 was significantly over-expressed in EECs as compared to normal controls. After transfection of a miR-205 inhibitor, the expression of miR-205 in endometrial cancer cell line RL95-2 cells was decreased while its predicted target gene, JPH4, showed increased protein expression. JPH4 appears a real miR-205 target in vitro and in vivo, and a candidate tumor suppressor gene in EEC. Based upon this study in endometrial cancers, miRNAs predicted to be involved in tumorigenesis and tumor progression in EEC have been distinguished and placed in the context of the transcriptome of EEC. This work provides a framework from which further research into the novel diagnosis and personalized treatment of EEC can be focused.
Chromosomal mosaicism in human preimplantation embryos: a systematic review
Authors: Jannie van Echten-Arends, Sebastiaan Mastenbroek, Birgit Sikkema-Raddatz, Johanna C. Korevaar, Maas Jan Heineman, Fulco van der Veen, Sjoerd Repping
Journal: Human Reproduction Update (2011)

Although chromosomal mosaicism in human preimplantation embryos has been described for almost two decades, its exact prevalence is still unknown. The prevalence of mosaicism is important in the context of preimplantation genetic screening in which the chromosomal status of an embryo is determined by the analysis of a single cell from that embryo. Here we report a systematic review and meta-analysis of studies on the chromosomal constitution of human preimplantation embryos. In 36 studies, out of 2117 citations that met our search criteria, data were provided extensively enough to allow classification of each analysed embryo with prespecified criteria for its chromosomal makeup. The main outcome of this classification was the prevalence of chromosomal mosaicism in human preimplantation embryos. A total of 815 embryos could be classified. Of these, 177 (22%) were diploid, 599 (73%) were mosaic, of which 480 (59% of the total number of embryos) were diploid–aneuploid mosaic and 119 (14% of the total number of embryos) were aneuploid mosaic, and 39 (5%) contained other numerical chromosomal abnormalities. The distribution of the embryos over these categories was associated with the developmental stage of the embryos, the method used for analysis and the number of chromosomes analysed. Diploid–aneuploid mosaicism is by far the most common chromosomal constitution in spare human preimplantation embryos after IVF. This undermines the reliable determination of the ploidy status of a cleavage-stage embryo based on the analysis of a single cell. Future research should determine the origin and developmental potential of mosaic embryos.
Bilateral thoracoscopic splanchnicectomy in chronic intestinal pseudo-obstruction: report of two paediatric cases
Authors: K Khelif
Journal: Gut (2006)

Chronic intestinal pseudo-obstruction (CIPO) is a rare, highly morbid disorder characterised by signs and symptoms of intestinal obstruction in the absence of mechanical obstruction.1 With no specific aetiology to tackle, management of CIPO focuses on symptom control and maintenance of an adequate nutritional status. Intractable chronic abdominal pain is a frequent and distressing feature in CIPO.

Here we report on the effect of bilateral thoracoscopic splanchnicectomy (TS) in two boys, one mentally retarded, with severe CIPO refractory to conventional therapy. Their debilitating chronic abdominal pain and markedly impaired quality of life (QoL) was iteratively alleviated by transient bilateral coeliac blocks (CB). After 26 and 9 successful CB, respectively, TS was performed. The greater and lesser splanchnic nerves were coagulated and divided bilaterally in both patients (fig 1).  Figure 1  
 Thoracoscopic localisation and section of splanchnic nerves. Right pleural cavity, patient head on …
Spontaneous intracerebral haemorrhage
Authors: R. A.-S. Salman, D. L Labovitz, C. Stapf
Journal: BMJ (2009)

Spontaneous (non-traumatic) intracerebral haemorrhage accounts for at least 10% of all strokes in the United Kingdom,1 but the incidence is higher in some ethnic groups.w1 Intracerebral haemorrhage may present with a sudden focal neurological deficit or a reduced level of consciousness, after which it kills about half of those affected within one month and leaves most survivors disabled.2

Although early case fatality after spontaneous intracerebral haemorrhage has not changed over the past two decades,1 2 brain imaging has illuminated the pathophysiology of intracerebral haemorrhage and its various causes,3 w2 such that the term primary intracerebral haemorrhage now seems antiquated. Improving prevention of intracerebral haemorrhage in primary care and its outcome in secondary care is especially important in view of trends towards a rising incidence of intracerebral haemorrhage in an ageing population.1

No clinical scoring system has been shown to reliably differentiate intracerebral haemorrhage from ischaemic stroke.w3 Timely brain imaging is the key to recognising intracerebral haemorrhage. Computed tomography detects symptomatic intracerebral haemorrhage within minutes of symptom onset and up to one week thereafter; magnetic resonance imaging with gradient-recalled echo sequences reliably differentiates infarction from haemorrhage more than one week after onset of stroke.4 Diagnostic imaging distinguishes intracerebral haemorrhage from other types of intracranial haemorrhage (fig 1⇓), although intracerebral haemorrhage may extend into other intracranial compartments. This distinction is important, because the causes, prognosis, and treatment vary according to the location of intracranial haemorrhage.5



Fig 1 Axial illustration of the brain showing the subtypes of intracranial haemorrhage 



The major risk factors for spontaneous intracerebral haemorrhage are systemic arterial hypertension, excess alcohol consumption, male sex, increasing age, and smoking.6 w4 w5 These risk factors may lead to secondary vascular changes, such as small vessel disease and arterial aneurysms, which may eventually …
Release of Blood from the Splanchnic Circulation in Dogs
Authors: Gerald A. Brooksby, David E. Donald
Journal: Circulation Research (1972)

In dogs anesthetized with α-chloralose, passive alterations in splanchnic blood flow over a range of flows between 10 ml/kg min -1 and 50 ml/kg min -1 produced by a blood flow pump or by a change in perfusion pressure were associated with changes in splanchnic blood volume of 0.19 ± 0.1 (SD) ml/kg and 0.43 ± 0.15 ml/kg, respectively, for a change in flow of 1 ml/kg min -1 . Mechanical increase in splanchnic outflow resistance raised portal venous pressure from a control mean of 6.9 ± 4.1 mm Hg to 15.4 ± 3.5 mm Hg and increased splanchnic blood volume by 8.1 ± 2.2 ml/kg. Of the total change in splanchnic blood volume during an 18-second supramaximal stimulation of the thoracic splanchnic nerves, an estimated 65% was released "passively." The magnitude of this passive release was related linearly to splanchnic blood flow. During increased resistance to splanchnic outflow, the passive release was absolutely and relatively reduced, but the volume of blood actively released by constriction of capacitance elements was absolutely and relatively increased. During hemorrhage (7.2 ml/kg body weight), an average of 4.7 ± 0.6 ml/kg of blood (21% of the calculated splanchnic blood volume) was mobilized, and arterial blood pressure decreased an average of 5%. Repetition of the bleeding after bilateral splanchnicectomy passively mobilized 3.25 ± 0.9 ml/kg of blood (68% of the innervated value), but arterial blood pressure declined by an average of 20%.
Interleukin-8 plays a significant role in IgE-mediated lung inflammation
Authors: RA Erger, TB Casale
Journal: European Respiratory Journal (1998)

Interleukin (IL)-8 is a potentially important cytokine in allergic respiratory responses since it is released by many resident lung cells, and it is a potent granulocyte chemoattractant. Therefore, we induced an immunoglobulin (Ig)E-mediated response in human lung samples and studied whether IL-8 was produced in sufficient quantities to promote human neutrophil and eosinophil migration across naked filters and endothelial and pulmonary epithelial monolayers cultured on these filters. Fresh human lung fragments from 16 thoracotomy specimens were treated with either a 1:100 dilution of anti-IgE or buffer (control) for 30 min. All anti-IgE treated lung samples had significant release of histamine and neutrophil and eosinophil chemotactic activity. Fourteen of the 16 lung samples had a significant increase in IL-8 subsequent to anti-IgE treatment (p&lt;0.01). Anti-IL-8 antibody (4 microg x mL[-1]) inhibited 42% and 53% of neutrophil and eosinophil chemotactic activity respectively, contained in supernatants from anti-IgE-treated lung samples. Finally, we found that IL-8 at a concentration near that measured after anti-IgE treatment of lung samples (2,000 pg x mL[-1]) induced neutrophil and eosinophil migration through naked filters and endothelial and pulmonary epithelial cell monolayers. Thus, human lung IgE-mediated responses in vitro results in the rapid release of interleukin-8 in amounts sufficient to affect a biological response, granulocyte transcellular migration, indicating that interleukin-8 may play a significant role in allergic respiratory diseases.
Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn’s disease
Authors: Michele M. Kosiewicz, Cynthia C. Nast, Anasuya Krishnan, Jesus Rivera-Nieves, Christopher A. Moskaluk, Satoshi Matsumoto, Kosuke Kozaiwa, Fabio Cominelli
Journal: Journal of Clinical Investigation (2001)

We describe here the immunologic characterization of a new mouse strain, SAMP1/Yit, which spontaneously develops a chronic intestinal inflammation localized to the terminal ileum. The resulting ileitis bears a remarkable resemblance to human Crohn’s disease. This strain of mice develops discontinuous, transmural inflammatory lesions in the terminal ileum with 100% penetrance by 30 weeks of age. The intestinal inflammation is characterized by massive infiltration of activated CD4+ and CD8α+TCRαβ+ T cells into the lamina propria and is accompanied by a dramatic decrease in the intraepithelial lymphocyte CD8α+TCRγδ+/CD8α+TCRαβ+ ratio. The results of adoptive transfer experiments strongly suggest that CD4+ T cells that produce a Th1-like profile of cytokines, e.g., IFN-γ and TNF, mediate the intestinal inflammation found in SAMP1/Yit mice. In addition, pretreatment of adoptive transfer recipients with a neutralizing anti-TNF antibody prevents the development of intestinal inflammation, suggesting that TNF plays an important role in the pathogenesis of intestinal inflammation in this model. To our knowledge, these data provide the first direct evidence that Th1-producing T cells mediate intestinal inflammation in a spontaneous animal model of human Crohn’s disease.
Clustering of phosphorylation site recognition motifs can be exploited to predict the targets of cyclin-dependent kinase
Authors: Alan M Moses, Jean-Karim Hériché, Richard Durbin
Journal: Genome biology (2007)

Protein kinases are critical to cellular signalling and post-translational gene regulation, but their biological substrates are difficult to identify. We show that cyclin-dependent kinase (CDK) consensus motifs are frequently clustered in CDK substrate proteins. Based on this, we introduce a new computational strategy to predict the targets of CDKs and use it to identify new biologically interesting candidates. Our data suggest that regulatory modules may exist in protein sequence as clusters of short sequence motifs.
Safety watchdog warns of high dosage errors among children and young people
Authors: A. O'Dowd
Journal: BMJ (2009)

Clinicians must improve safety when treating children and young people to avoid what have been high rates of dosage errors, according to the UK patient safety watchdog. The National Patient Safety Agency (NPSA) has raised concerns in a report that outlines ways to improve patient safety in this age group.

As part of its review the agency looked at incidents that occurred between October 2007 and September 2008. It used information from the 910 089 patient safety incidents that had been reported over a year; 60 000 of those incidents involved children.

It also studied direct feedback from children, young people, and …
The apolipoprotein E gene and the serum low-density lipoprotein cholesterol response to dietary fiber
Authors: David J.A. Jenkins, Robert A. Hegele, Alexandra L. Jenkins, Philip W. Connelly, Kassem Hallak, Paige Bracci, Hanoch Kashtan, Paul Corey, Melenia Pintilia, Hartley Stern, Robert Bruce
Journal: Metabolism (1993)
Endothelial [Ca2+]i and caveolin-1 antagonistically regulate eNOS activity and microvessel permeability in rat venules
Authors: Xueping Zhou, Pingnian He
Journal: Cardiovascular Research (2010)

AimsIn this study, we investigated the mechanisms by which caveolin-1 (CAV) inhibits increases in permeability induced by platelet activating factor (PAF) and elucidated the relationship between the endothelial intracellular Ca2+ concentration ([Ca2+]i) and CAV in regulating endothelial nitric oxide synthase (eNOS) activity and microvessel permeability in intact microvessels.
SIV infection of rhesus macaques results in dysfunctional T- and B-cell responses to neo and recall Leishmania major vaccination
Authors: Nichole R. Klatt, Carol L. Vinton, Rebecca M. Lynch, Lauren A. Canary, Jason Ho, Patricia A. Darrah, Jacob D. Estes, Robert A. Seder, Susan L. Moir, Jason M. Brenchley
Journal: Blood (2011)
Interferon as a mediator of human lymphocyte suppression.
Authors: A S Kadish, F A Tansey, G S Yu, A T Doyle, B R Bloom
Journal: The Journal of Experimental Medicine (1980)

Evidence is presented that interferon (IF) is a major mediator of the human concanavalin A (Con A) suppressor cell. The suppressive effects of Con A-activated lymphocytes on the mitogen responses of normal responder cells were largely abrogated by addition of anti-human leukocyte IF serum. Similar suppressor activity was generated by coculture of peripheral blood leukocytes (PBL) with a melanoma cell line (MeWo) and a HeLa cell line persistently infected with measles virus that induced the production of IF by lymphocytes. A human mammary carcinoma line (MCF-7) and two bladder carcinoma lines (T24 and TCCSUP) failed to induce IF or suppression. Addition of anti-human leukocyte IF serum to suppressor cells and supernates from tumor cell-lymphocyte cocultures largely abolished suppression and neutralized the antiviral activity of such supernates. Exposure of PBL from purified protein derivative (PPD)-positive donors to PPD caused the production of suppressor activity and IF. PBL from PPD-negative donors failed to produce significant amounts of IF or to suppress on exposure to PPD. Supernates from PBL treated with virus (Newcastle disease virus [NDV]) contained IF and suppressed the mitogen responses of responder PBL. Both the suppressive and the antiviral activities of this material were eliminated after treatment with anti-IF serum. To ascertain whether antiviral and suppressive activities were mediated by the same types of IF, supernates from PBL cultured with Con A, PPD, NDV, and tumor cells were treated with anti-IF serum or acid pH. In all cases antiviral activity was neutralized in parallel with abrogation of suppressor activity. These results provide strong evidence for the role of IF as a mediator of human suppressor cell activity.
Correlation between pathological and clinical findings in 195 consecutive liver biopsies showing brown pigment
Authors: N. Tygstrup, T. Schiodt, K. Winkler
Journal: Gut (1965)

EDITORIAL SYNOPSIS 'Brown lipofuscin' pigment is not uncommon in liver biopsy specimens from the hospital population.This particular study describes such pigment in 15 % of 195 needle biopsy samples.The association with unexplained hepatomegaly and with an asthenic 'presenile' look has not hitherto been described.on July 12,