bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transforming Growth Factor-β Signaling–Deficient Fibroblasts Enhance Hepatocyte Growth Factor Signaling in Mammary Carcinoma Cells to Promote Scattering and Invasion
Authors: Cheng Nikki , Chytil Anna , Shyr Yu , Joly Alison , Moses Harold L. 
Published: October 2008

Abstract
Fibroblasts are major cellular components of the tumor microenvironment, regulating tumor cell behavior in part through secretion of extracellular matrix proteins, growth factors, and angiogenic factors. In previous studies, conditional deletion of the type II transforming growth factor-β (TGF-β) receptor in fibroblasts (Tgfbr2FspKO) was shown to promote mammary tumor metastasis in fibroblast-epithelial cell cotransplantation studies in mice, correlating with increased expression of hepatocyte growth factor (HGF). Here, we advance our findings to show that Tgfbr2FspKO fibroblasts enhance HGF/c-Met and HGF/Ron signaling to promote scattering and invasion of mammary carcinoma cells. Blockade of c-Met and Ron by small interfering RNA silencing and pharmacologic inhibitors significantly reduced mammary carcinoma cell scattering and invasion caused by Tgfbr2FspKO fibroblasts. Moreover, neutralizing antibodies to c-Met and Ron significantly inhibited HGF-induced cell scattering and invasion, correlating with reduced Stat3 and p42/44MAPK phosphorylation. Investigation of the signal transducer and activator of transcription 3 (Stat3) and mitogen-activated protein kinase (MAPK) signaling pathways by pharmacologic inhibition and small interfering RNA silencing revealed a cooperative interaction between the two pathways to regulate HGF-induced invasion, scattering, and motility of mammary tumor cells. Furthermore, whereas c-Met was found to regulate both the Stat3 and MAPK signaling pathways, Ron was found to regulate Stat3 but not MAPK signaling in mammary carcinoma cells. These studies show a tumor-suppressive role for TGF-β signaling in fibroblasts, in part by suppressing HGF signaling between mammary fibroblasts and epithelial cells. These studies characterize complex functional roles for HGF and TGF-β signaling in mediating tumor-stromal interactions during mammary tumor cell scattering and invasion, with important implications in the metastatic process. (Mol Cancer Res 2008;6(10):1521–33)
Global Gene Expression Profiling Unveils S100A8/A9 as Candidate Markers in H-Ras-Mediated Human Breast Epithelial Cell Invasion
Authors: Moon Aree , Yong Hae-Young , Song Jae-In , Cukovic Daniela , Salagrama Sridevi , Kaplan David , Putt David , Kim Hyesook , Dombkowski Alan , Kim Hyeong-Reh Choi 
Published: October 2008

Abstract
The goal of the present study is to unveil the gene expression profile specific to the biological processes of human breast epithelial cell invasion and migration using an MCF10A model genetically engineered to constitutively activate the H-ras or N-ras signaling pathway. We previously showed that H-Ras, but not N-Ras, induces MCF10A cell invasion/migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. Thus, these cell lines provide an experimental system to separate the gene expression profile associated with cell invasion apart from cell proliferation/transformation. Analysis of whole human genome microarray revealed that 412 genes were differentially expressed among MCF10A, N-Ras MCF10A, and H-Ras MCF10A cells and hierarchical clustering separated 412 genes into four clusters. We then tested whether S100A8 and S100A9, two of the genes which are most highly up-regulated in an H-Ras–specific manner, play a causative role for H-Ras–mediated MCF10A cell invasion and migration. Importantly, small interfering RNA–mediated knockdown of S100A8/A9 expression significantly reduced H-Ras–induced invasion/migration. Conversely, the induction of S100A8/A9 expression conferred the invasive/migratory phenotype to parental MCF10A cells. Furthermore, we provided evidence of signaling cross-talk between S100A8/A9 and the mitogen-activated protein kinase signaling pathways essential for H-Ras–mediated cell invasion and migration. Taken together, this study revealed S100A8/A9 genes as candidate markers for metastatic potential of breast epithelial cells. Our gene profile data provide useful information which may lead to the identification of additional potential targets for the prognosis and/or therapy of metastatic breast cancer. (Mol Cancer Res 2008;6(10):1544–53)
Genome-Wide Analysis in a Murine Dnmt1 Knockdown Model Identifies Epigenetically Silenced Genes in Primary Human Pituitary Tumors
Authors: Dudley Kevin J. , Revill Kate , Whitby Philip , Clayton Richard N. , Farrell William E. 
Published: October 2008

Abstract
DNA methylation at promoter CpG islands (CGI) is an epigenetic modification associated with inappropriate gene silencing in multiple tumor types. In the absence of a human pituitary tumor cell line, small interfering RNA–mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20. Sustained knockdown induced reexpression of the fully methylated and normally imprinted gene neuronatin (Nnat) in a time-dependent manner. Combined bisulfite restriction analysis (COBRA) revealed that reexpression of Nnat was associated with partial CGI demethylation, which was also observed at the H19 differentially methylated region. Subsequent genome-wide microarray analysis identified 91 genes that were significantly differentially expressed in Dnmt1 knockdown cells (10% false discovery rate). The analysis showed that genes associated with the induction of apoptosis, signal transduction, and developmental processes were significantly overrepresented in this list (P &lt; 0.05). Following validation by reverse transcription-PCR and detection of inappropriate CGI methylation by COBRA, four genes (ICAM1, NNAT, RUNX1, and S100A10) were analyzed in primary human pituitary tumors, each displaying significantly reduced mRNA levels relative to normal pituitary (P &lt; 0.05). For two of these genes, NNAT and S100A10, decreased expression was associated with increased promoter CGI methylation. Induced expression of Nnat in stable transfected AtT-20 cells inhibited cell proliferation. To our knowledge, this is the first report of array-based “epigenetic unmasking” in combination with Dnmt1 knockdown and reveals the potential of this strategy toward identifying genes silenced by epigenetic mechanisms across species boundaries. (Mol Cancer Res 2008;6(10):1567–74)
The Effect of Storm Life Cycle on Satellite Rainfall Estimation Error
Authors: Tadesse Alemu , Anagnostou Emmanouil N. 
Published: October 2008

Abstract
The study uses storm tracking information to evaluate error statistics of satellite rain estimation at different maturity stages of storm life cycles. Two satellite rain retrieval products are used for this purpose: (i) NASA’s Multisatellite Precipitation Analysis–Real Time product available at 25-km/hourly resolution (3B41-RT) and (ii) the University of California (Irvine) Precipitation Estimation from Remotely Sensed Information using Artificial Neural Networks (PERSIANN) product available at 4-km–hourly resolution. Both algorithms use geostationary satellite infrared (IR) observations calibrated to an array of passive microwave (PM) earth-orbiting satellite sensor rain retrievals. The techniques differ in terms of algorithmic structure and in the way they use the PM rainfall to calibrate the IR rain algorithms. The satellite retrievals are evaluated against rain gauge–calibrated radar rainfall estimates over the continental United States. Error statistics of hourly rain volumes are determined separately for thunderstorm and shower-type convective systems and for different storm life durations and stages of maturity. The authors show distinct differences between the two satellite retrieval error characteristics. The most notable difference is the strong storm life cycle dependence of 3B41-RT relative to the nearly independent PERSIANN behavior. Another is in the algorithm performance between thunderstorms and showers; 3B41-RT exhibits significant bias increase at longer storm life durations. PERSIANN exhibits consistently improved correlations relative to the 3B41-RT for all storm life durations and maturity stages. The findings of this study support the hypothesis that incorporating cloud type information into the retrieval (done by the PERSIANN algorithm) can help improve the satellite retrieval accuracy.
Novel genomic alterations and clonal evolution in chronic lymphocytic leukemia revealed by representational oligonucleotide microarray analysis (ROMA)
Authors: Grubor Vladimir , Krasnitz Alex , Troge Jennifer E. , Meth Jennifer L. , Lakshmi B. , Kendall Jude T. , Yamrom Boris , Alex Garrick , Pai Deepa , Navin Nicholas , Hufnagel Lisa A. , Lee Yoon-Ha , Cook Kerry , Allen Steven L. , Rai Kanti R. , Damle Rajendra N. , Calissano Carlo , Chiorazzi Nicholas , Wigler Michael , Esposito Diane 
Published: October 2008

Abstract
We examined copy number changes in the genomes of B cells from 58 patients with chronic lymphocytic leukemia (CLL) by using representational oligonucleotide microarray analysis (ROMA), a form of comparative genomic hybridization (CGH), at a resolution exceeding previously published studies. We observed at least 1 genomic lesion in each CLL sample and considerable variation in the number of abnormalities from case to case. Virtually all abnormalities previously reported also were observed here, most of which were indeed highly recurrent. We observed the boundaries of known events with greater clarity and identified previously undescribed lesions, some of which were recurrent. We profiled the genomes of CLL cells separated by the surface marker CD38 and found evidence of distinct subclones of CLL within the same patient. We discuss the potential applications of high-resolution CGH analysis in a clinical setting.
Heterologous expression of plasmodial proteins for structural studies and functional annotation
Authors: Birkholtz Lyn-Marie , Blatch Gregory , Coetzer Theresa L , Hoppe Heinrich C , Human Esmaré , Morris Elizabeth J , Ngcete Zoleka , Oldfield Lyndon , Roth Robyn , Shonhai Addmore , Stephens Linda , Louw Abraham I 
Published: October 2008

AbstractMalaria remains the world's most devastating tropical infectious disease with as many as 40% of the world population living in risk areas. The widespread resistance ofPlasmodiumparasites to the cost-effective chloroquine and antifolates has forced the introduction of more costly drug combinations, such as Coartem®. In the absence of a vaccine in the foreseeable future, one strategy to address the growing malaria problem is to identify and characterize new and durable antimalarial drug targets, the majority of which are parasite proteins. Biochemical and structure-activity analysis of these proteins is ultimately essential in the characterization of such targets but requires large amounts of functional protein. Even though heterologous protein production has now become a relatively routine endeavour for most proteins of diverse origins, the functional expression of soluble plasmodial proteins is highly problematic and slows the progress of antimalarial drug target discovery. Here thestatus quoof heterologous production of plasmodial proteins is presented, constraints are highlighted and alternative strategies and hosts for functional expression and annotation of plasmodial proteins are reviewed.
So much to teach, so little time: a prospective cohort study evaluating a tool to select content for a critical care curriculum
Authors: Peets Adam D , McLaughlin Kevin , Lockyer Jocelyn , Donnon Tyrone 
Published: October 2008

Abstract
Introduction
Curricular content is often based on the personal opinions of a small number of individuals. Although convenient, such curricula may not meet the needs of the target learner, the program or the institution. Using an objective method to ensure content validity of a curriculum can alleviate this issue.

Methods
A form was created that listed clinical presentations relevant to residents completing intensive care unit (ICU) rotations. Twenty residents and 20 intensivists in tertiary academic multisystem ICUs ranked each presentation on three separate scales: how life-threatening each is, how commonly each is seen in critical care, and how reversible each is. Mean scores for the individual scales were calculated, and these three values were subsequently multiplied together to achieve a composite score for each presentation. The correlation between the two groups' scores for the presentations was calculated to assess reliability of the process.

Results
There was excellent agreement between the two groups for rating each presentation (correlation coefficient r = 0.94). The 10 clinical presentations with the highest composite scores formed the basis of our new curriculum.

Conclusions
We describe a method that can be used to select the content of a curriculum for learners in an ICU. Although the content that we selected to include in our curriculum may not be applicable to other ICUs, we believe that the process we used is easily applied elsewhere, and that it provides an efficient method to improve content validity of a curriculum.
A Misleading Case of Central Pontine Myelinolysis
Authors: McColl Peter , Kelly Christopher 
Published: October 2008

Central pontine myelinolysis (CPM) is an uncommon disorder initially described in alcoholic or malnourished patients. Recent reports suggest an aetiological association with abnormalities of serum sodium. A physically unwell non-alcoholic chronic schizophrenic patient, whose symptoms led to psychiatric referral, died of CPM. A review of the literature reveals that psychiatric patients may indeed be at risk for CPM.British Journal of Psychiatry(1992),160, 550–552
What Events Precede Violent Incidents in Psychiatric Hospitals?
Authors: Powell Georgia , Caan Woody , Crowe Michael 
Published: October 2008

BackgroundThe study aimed to identify, classify and measure the relative frequency of events preceding violent incidents in psychiatric hospitals.MethodPossible antecedents for 1000 incidents in three associated psychiatric hospitals over 13 months were investigated with an ‘untoward incident database’.ResultsFrom eyewitness accounts, 921 incidents (92%) could be related to one of 15 categories of antecedent involving characteristics of the patient, or of the hospital regime, or interactions with other individuals. Overall, the most common antecedents involved patients who were generally agitated or disturbed (286), restrictions on patients associated with the routine hospital regime (192) or provocation by other patients, relatives or visitors (175). Incidents arising from staff members initiating contact with patients were very rare (7). Twenty-one patients were involved in 10 or more incidents, including 19 (90%) who were detained under the Mental Health Act. These patients were more likely to commit assaults after certain antecedents (self-harm, absconding or arson) which were serious incidents in themselves.ConclusionsStaff training on specific safety issues will be needed under the new Management of Health and Safety at Work Regulations.
The Effect of Child Sexual Abuse on Social, Interpersonal and Sexual Function in Adult Life
Authors: Mullen P. E. , Martin J. L. , Anderson J. C. , Romans S. E. , Herbison G. P. 
Published: October 2008

BackgroundThe association was examined between reporting child sexual abuse (CSA) and a range of social, interpersonal and sexual difficulties in adult life.MethodA random sample of 2250 women were posted a questionnaire exploring a range of abuse experiences. All 248 reporting CSA were invited for interview, together with an equal number of controls. At interview a detailed inquiry was made into the CSA and into current interpersonal, social and sexual function.ResultsSignificant associations emerged between reporting CSA and a decline in socioeconomic status, increased sexual problems, and the disruption of intimate relationships by difficulties with trust as well as a propensity to perceive their partners as uncaring and overcontrolling. CSA was more common in those from disturbed and disrupted families and in those who also reported physical and emotional abuse. This explained part, but not all, of the apparent association between CSA and negative outcomes.ConclusionsThose reporting CSA are more likely to suffer social, interpersonal and sexual difficulties in adult life.
Neuropathological Correlates of Psychotic Phenomena in Confirmed Alzheimer's Disease
Authors: Förstl Hans , Burns Alistair , Levy Raymond , Cairns Nigel 
Published: October 2008

BackgroundThe prevalence of psychotic phenomena in confirmed Alzheimer's disease (AD) and their potential neuropathological correlates have rarely been the subject of prospective investigation.MethodPsychopathological disturbances were recorded prospectively according to the Geriatric Mental State Schedule and the CAMDEX. The frequency of these phenomena and neuropathological changes were examined in 56 patients with definite AD.ResultsHallucinations had been documented in 13 patients, paranoid delusions in 9 and delusional misidentification (e.g. the Capgras-type and the ‘phantom boarder’ symptoms) in 14 patients. Misidentifications were associated with lower neurone counts in the area CA1 of the hippocampus. Delusions and hallucinations were observed in patients with less severe cell loss in the parahippocampal gyrus and with lower cell counts in the dorsal raphe nucleus. A decrease of neurones in the locus coeruleus in a subset of depressed patients with AD had been reported earlier. Delusions and delusional misidentification were common in 5 patients with basal ganglia mineralisation, but there was no statistically significant association of these symptoms with the presence of Lewy bodies in the brainstem and neocortex of our patient sample.ConclusionsThese findings are compatible with the view that morphological changes in certain brain areas may promote the development of psychotic phenomena in AD. AD may offer a model for the understanding of pathomechanisms underlying the development of psychopathological disturbances in other psychoses with more discrete neuropathological changes.
Community Psychiatric Nurse Teams: Cost-effectiveness of Intensive Support Versus Generic Care
Authors: McCrone Paul , Beecham Jennifer , Knapp Martin 
Published: October 2008

Background.Part of the community psychiatric nurse (CPN) service was reorganised into a community support team (CST), with staff acting as case managers. An economic evaluation ran parallel to the comparison with generic CPN care.Method.Eighty-two clients were randomly allocated to experimental and control groups. Costs were comprehensively measured over a pre-referral period (three months), and then at 6, 12, and 18 months.Results.The economic evaluation found a cost difference between the groups. Generic group costs averaged £89 per patient per week more than CST group costs. The difference was only significant for the first six months. Changes in the burden of cost across agencies were observed.Conclusions.Although CPN inputs and costs were higher for the CST group, there was a significant short-term reduction in total cost. Beyond the short term, the CST did not confer cost or cost-effectiveness advantages.
The Relationship of Schizophrenic Births to 16 Infectious Diseases
Authors: O'Callaghan E. , Sham P. C. , Takei N. , Murray G. , Glover G. , Hare E. H. , Murray R. M. 
Published: October 2008

BackgroundRecently, several investigators have reported an association between influenza epidemics and increased birth rates of ‘preschizophrenic’ individuals some four to six months later. Here we examine whether maternal exposure to other infectious diseases can also predispose the foetus to later schizophrenia.MethodTwo independent sets of dates of birth of first admission schizophrenic patients, born between 1938 and 1965 in England and Wales, were obtained from the Mental Health Enquiry in England and Wales. Data on the number of deaths per month from 16 infectious diseases between 1937 and 1965 in England and Wales were also collected. We used a Poisson regression model to examine the relationship between deaths from infectious diseases and schizophrenic births.ResultsIn the two separate data sets, increased national deaths from bronchopneumonia preceded, by three and five months respectively, increased numbers of schizophrenic births. We did not find any other significant associations between schizophrenic births and any of the other 15 infectious diseases.ConclusionsThe association between deaths from bronchopneumonia and increased schizophrenic births some months later may be a reflection of the fact that bronchopneumonia deaths increase markedly during influenza epidemics.
Low Birth Weight and Schizophrenia
Authors: Rifkin Larry , Lewis Shôn , Jones Peter , Toone Brian , Murray Robin 
Published: October 2008

BackgroundLow birth weight has been postulated to be a risk factor for schizophrenia.MethodObstetric history, premorbid adjustment, and cognitive function during admission were assessed in 167 patients with DSM–III schizophrenia or affective psychosis.ResultsA birth weight of less than 2500 g was significantly more common in patients with schizophrenia than in those with affective psychosis. Schizophrenic patients as a group had significantly lower mean birth weight, a finding which was particularly marked after controlling for sociodemographic confounders. In schizophrenic men, lower birth weight was highly significantly correlated with poorer premorbid social and cognitive ability, and with impairment of adult cognitive function.ConclusionsNeurodevelopmental impairment may cause poor foetal growth, and schizophrenia in adult life.
Clonidine is not a Useful Adjunct to Methadone Gradual Detoxification in Opioid Addiction
Authors: Ghodse Hamid , Myles Judith , Smith Stephen E. 
Published: October 2008

BackgroundThe role of clonidine in the management of opioid-dependent individuals undergoing gradual detoxification.MethodA double-blind placebo-controlled trial was conducted on 86 voluntary in-patients (59 male, 27 female) aged 18–47 years, at a specialist drug-dependence treatment unit. Patients entered the trial when on 40 mg of methadone daily or less, and were randomised to receive incremental doses of clonidine (increasing from 0.2 mg daily to 1.2 mg daily) during a 14-day period of gradual methadone detoxification and for four weeks thereafter. Blood pressure was monitored and severity of opioid abstinence was assessed by questionnaire and by clinical examination.ResultHalf the subjects were withdrawn or defaulted from the trial by the end of two weeks, those receiving clonidine earlier than those receiving dummy medication (9 of the former and only one of the latter because of systemic hypotension). Similar proportions of subjects completed detoxification in the two groups. In those who completed detoxification, clonidine did not significantly reduce either the symptoms or objective signs of opioid withdrawal.ConclusionsThese findings suggest that clonidine has no place as an adjunct to a programme of gradual opioid detoxification.