bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor-Associated Galectin-3 Modulates the Function of Tumor-Reactive T Cells
Authors: Peng Weiyi , Wang Helen Y. , Miyahara Yoshihiro , Peng Guangyong , Wang Rong-Fu 
Published: August 2008

Abstract
T cells play an important role in cancer immunosurveillance and tumor destruction. However, tumor cells alter immune responses by modulating immune cells through antigen stimulation and immunoregulatory cytokines. A better understanding of the interplay between tumor cells and T cells might provide new strategies to enhance antitumor immunity. Through an antigen-screening approach using colorectal tumor–reactive T cells, we identified an HLA-DR11–restricted T-cell epitope encoded by KIAA0040 as well as MHC-unrestricted human galectin-3 (Gal-3) expressed by tumor cells. Although the biological function of KIAA0040 remains to be determined, we found that Gal-3 functioned as an immune regulator for direct T-cell activation and function. T-cell activation induced by Gal-3 resulted in T-cell apoptosis. We showed that a high level of expression of Gal-3 promoted tumor growth in vitro and in vivo. Using a mouse tumor model, we showed that delivery of high doses of Gal-3 inhibited tumor-reactive T cells and promoted tumor growth in mice receiving tumor-reactive CD8+ T cells. These findings suggest that Gal-3 may function as an immune regulator to inhibit T-cell immune responses and promote tumor growth, thus providing a new mechanism for tumor immune tolerance. [Cancer Res 2008;68(17):7228–36]
Characterization of the Recurrent 8p11-12 Amplicon Identifies PPAPDC1B, a Phosphatase Protein, as a New Therapeutic Target in Breast Cancer
Authors: Bernard-Pierrot Isabelle , Gruel Nadège , Stransky Nicolas , Vincent-Salomon Anne , Reyal Fabien , Raynal Virginie , Vallot Céline , Pierron Gaëlle , Radvanyi François , Delattre Olivier 
Published: August 2008

Abstract
The 8p11-12 chromosome region is one of the regions most frequently amplified in breast carcinoma (10–15% of cases). Several genes within this region have been identified as candidate oncogenes, as they are both amplified and overexpressed. However, very few studies have explored the role of these genes in cell transformation, with the aim of identifying valuable therapeutic targets. An analysis of comparative genomic hybridization array and expression profiling data for a series of 152 ductal breast carcinomas and 21 cell lines identified five genes (LSM1, BAG4, DDHD2, PPAPDC1B, and WHSC1L1) within the amplified region as consistently overexpressed due to an increased gene copy number. The use of small interfering RNA to knock down the expression of each of these genes showed the major role played by two genes, PPAPDC1B and WHSC1L1, in regulating the survival and transformation of two different cell lines harboring the 8p amplicon. The role of these two genes in cell survival and cell transformation was also confirmed by long-term knockdown expression studies using short hairpin RNAs. The potential of PPAPDC1B, which encodes a transmembrane phosphatase, as a therapeutic target was further shown by the strong inhibition of growth of breast tumor xenografts displaying 8p11-12 amplification induced by the silencing of PPAPDC1B. The oncogenic properties of PPAPDC1B were further shown by its ability to transform NIH-3T3 fibroblasts, inducing their anchorage-independent growth. Finally, microarray experiments on PPAPDC1B knockdown indicated that this gene interfered with multiple cell signaling pathways, including the Janus-activated kinase-signal transducer and activator of transcription, mitogen-activated protein kinase, and protein kinase C pathways. PPAPDC1B may also potentiate the estrogen receptor pathway by down-regulating DUSP22. [Cancer Res 2008;68(17):7165–75]
Identification of Secreted Proteins that Mediate Cell-Cell Interactions in an In vitro Model of the Lung Cancer Microenvironment
Authors: Zhong Li , Roybal Jonathon , Chaerkady Raghothama , Zhang Wan , Choi Kuicheon , Alvarez Cristina A. , Tran Hai , Creighton Chad J. , Yan Shaoyu , Strieter Robert M. , Pandey Akhilesh , Kurie Jonathan M. 
Published: August 2008

Abstract
Non–small cell lung cancer (NSCLC) cells with somatic mutations in K-ras recruit to the tumor a variety of cell types (hereafter collectively termed “stromal cells”) that can promote or inhibit tumorigenesis by mechanisms that have not been fully elucidated. Here, we postulated that stromal cells in the tumor microenvironment alter the tumor cell secretome, including those proteins required for tumor growth and dissemination, and we developed an in vitro model to test this hypothesis. Coculturing a murine K-ras mutant lung adenocarcinoma cell line (LKR-13) with a murine lung stromal cell (macrophage, endothelial cell, or fibroblast) enhanced stromal cell migration, induced endothelial tube formation, increased LKR-13 cell proliferation, and regulated the secretion of proteins involved in angiogenesis, inflammation, cell proliferation, and epithelial-to-mesenchymal transition. Among these proteins, CXCL1 has been reported to promote NSCLC development, whereas interleukin-18 (IL-18) has an undefined role. Genetic and pharmacologic strategies to inhibit CXCL1 and IL-18 revealed that stromal cell migration, LKR-13 cell proliferation, and LKR-13 cell tumorigenicity required one or both of these proteins. We conclude that stromal cells enhanced LKR-13 cell tumorigenicity partly through their effects on the secretome of LKR-13 cells. Strategies to inhibit tumor/stromal cell interactions may be useful as therapeutic approaches in NSCLC patients. [Cancer Res 2008;68(17):7237–45]
Psychotic-Like Ideations Among a Group of Young Normal Subjects in Iran
Authors: Sharifi Vandad , Sajjadifar Ali , Amini Homayoun 
Published: August 2008

Background: Recent studies show that self-reported psychotic-like experiences in general population samples are quite common and on a continuum with psychotic symptoms in clinical samples. However, most evidence comes from western settings and there is a dearth of research in developing countries. Examination of these experiences across different cultures adds to their validity. Aims: To assess psychotic-like ideations and its association with poor mental health in a group of young normal individuals in Iran. Methods: A total of 150 medical students with no history of a psychiatric disorder completed the Peters et al. Delusions Inventory (PDI-40) and the General Health Questionnaire (GHQ-28). Psychotic-like ideations were rated on the basis of their presence, as well as their levels of distress, preoccupation and conviction (PDI sub-scores). Results: On average, 9.4 psychotic-like ideations were reported by the subjects (range 0—28). More frequent psychotic-like ideations and higher distress and preoccupation associated with these ideations were correlated with poor mental health as assessed by the GHQ. Conclusion: Frequency of psychotic-like ideation and its dimensions, as well as its association with poor mental health, were comparable to the studies on healthy subjects conducted in Europe.
Psychiatriform Disorders: Psychiatric Analogues of Somatoform Disorders
Authors: Mullen Richard , Menkes David B. 
Published: August 2008

Background: Somatoform disorders can be understood to mimic supposedly more `legitimate' physical disorders. To the extent that mental disorders are now also often considered legitimate, might clinicians expect to encounter the psychiatric equivalent of somatoform disorders, `psychiatriform disorders'? Method: The relevant literature on somatoform disorders is reviewed in light of the tendency for mental and physical symptoms to co-occur. Discussion: Illness attribution and behaviour may explain some of the recent rise in the prevalence of mental disorder. Hypotheses regarding the cause and nature of somatoform disorders are applied to their proposed psychiatric equivalent. Despite lack of current recognition, there is a strong theoretical basis for the existence of psychiatriform disorders. Psychiatriform disorders can be expected to have similar causes, comorbidity, and response to treatment, as somatoform disorders. A variety of cultural forces may be contributing to a rise in prevalence. Conclusion: As with somatoform disorders, psychiatriform disorders present problems in their distinction from conscious fabrication and from the `legitimate' disorders they mimic. Given their likely prevalence and associated impairments, psychiatriform disorders warrant further examination, despite the methodological difficulties this presents.
Pharmacy Students' Attitudes Toward and Professional Interactions With People With Mental Disorders
Authors: Volmer Daisy , Mäesalu Martin , Bell J. Simon 
Published: August 2008

Background: Health professionals frequently exhibit negative attitudes toward people with mental disorders. It is not known whether stigmatising attitudes among pharmacy students predict less positive attitudes toward consumer participation in decision-making about medications. Aims: (1) To assess the attitudes of pharmacy students toward people with schizophrenia, and (2) to determine whether stigma predicts less positive attitudes toward concordant medication counselling. Method: All pharmacy students enrolled in a five-year degree program were invited to participate. Students completed the seven-item Social Distance Scale, six items related to stereotypical attributes of people with schizophrenia and the 14-item Leeds Attitudes Toward Concordance Scale. Results: Completed survey instruments were received from 157 students (94% response rate). Previous employment in a pharmacy and personal experience of a mental disorder were associated with low social distance. Later year of study, believing that people with schizophrenia are difficult to talk to, and believing people with schizophrenia have themselves to blame were predictive of high social distance. Low social distance and later year of study were associated with positive attitudes toward providing concordant medication counselling. Conclusion: Mental health stigma was common and predictive of less positive attitudes toward consumer participation in decision-making about medications.
Prevalence of Mental Disorder and Associated Factors in Civilian Guatemalans With Disabilities Caused By the Internal Armed Conflict
Authors: Herrera Rivera Walter , De Jesus Mari Jair , Baxter Andreoli Sergio , Ines Quintana Maria , Pacheco De Toledo Ferraz Marcos 
Published: August 2008

Background: The 34-year-long, Guatemalan war left at least 1,841 persons disabled in the country. The aim of this study was to describe the prevalence of mental disorders in individuals who acquired their disability as a result of the war, and to identify probable risk factors. Method: A cross-sectional study was conducted of a group of 99 civilians with a disability in Guatemala. Participants were selected from four civilian organizations serving disabled persons in the municipality of Nebaj, Quiche. The diagnostic instrument was the computerized version of the Composite International Diagnostic Instrument 2.1 (CIDI 2.1). Data were collected from 2002 to 2004. Results: Of the 99 disabled persons who completed the interview, 44 had some type of lifetime psychiatric disorder. Post-traumatic stress disorder (PTSD) was the most prevalent, with 34.34% (34 cases), followed by dysthymia, with 10.10% (10 cases), and depression, with 6.06% (6 cases). Conclusion: The traumatic events experienced during the conflict caused long-term psychological sequelae in people who were disabled as a result of the war. Increased exposure to traumatic events, being married, physical disability, illiteracy and advanced age were identified as probable risk factors for mental disorders .
Attitudes of Ward Attendants Towards Mental Illness: Comparisons and Predictors
Authors: Vibha Pandey , Saddichha Sahoo , Kumar Ranjeet 
Published: August 2008

Background: In India few studies exist that explore attitudes of mental health professionals, especially psychiatric ward attendants, towards psychiatric illnesses. This study aimed to explore attitudes of psychiatric ward attendants since they work closely with psychiatric patients in the hospital ward, and which may differ given their cultural and social background. Methods: Five hundred psychiatric ward attendants were targeted and a 100 sample size chosen based on systematic random sampling. A control group from guardians attending the outpatient department of Central Institute of Psychiatry was selected using the same methods. Attitudes of both groups were assessed using Community Attitudes towards Mental Illness (CAMI) after written informed consent. Results: There were no significant differences noted in Authoritarianism and Benevolence domains of CAMI. However, there were significant differences in the domains of Social Restrictiveness and Community Mental Health Ideology with psychiatric ward attendants scoring higher than the general attendants. Among the socio-demographic variables, there was significant correlation between age, duration of contact and educational background and various domains of CAMI. Conclusions: Psychiatric ward attendants had more positive attitudes than general attendants towards psychiatric illnesses. Socio-demographic variables like older age, higher education and longer duration of contact with the psychiatrically ill predicted more favourable attitudes.
How we diagnose the antiphospholipid syndrome
Authors: Giannakopoulos Bill , Passam Freda , Ioannou Yiannis , Krilis Steven A. 
Published: August 2008

AbstractThe antiphospholipid syndrome (APS) is an acquired thrombophilia, characterized by the occurrence of venous and arterial events. This article examines the laboratory and key clinical aspects of APS. Particular focus is given to anti–beta 2-glycoprotein I (β2GPI) antibodies in view of their recent inclusion in the APS classification criteria. The clinical utility of using the β2GPI enzyme-linked immunosorbent assay, in conjunction with the established lupus anticoagulant assays and cardiolipin enzyme-linked immunosorbent assay, for diagnosing and risk stratifying patients suspected of having APS is discussed. The relative importance of the various assays in diagnosing obstetric APS (early and late gestation miscarriages) is explored. The implications of recent epidemiologic findings for possibly understanding the underlying pathophysiologic mechanisms of obstetric APS are highlighted. Insights into which patients with obstetric APS may be at most risk of thrombotic complications are presented.
CD18-dependent activation of the neutrophil NADPH oxidase during phagocytosis of Escherichia coli or Staphylococcus aureus is regulated by class III but not class I or II PI3Ks
Authors: Anderson Karen E. , Boyle Keith B. , Davidson Keith , Chessa Tamara A. M. , Kulkarni Suhasini , Jarvis Gavin E. , Sindrilaru Anca , Scharffetter-Kochanek Karin , Rausch Oliver , Stephens Len R. , Hawkins Phillip T. 
Published: August 2008

AbstractPhagocytosis and activation of the NADPH oxidase are important mechanisms by which neutrophils and macrophages engulf and kill microbial pathogens. We investigated the role of PI3K signaling pathways in the regulation of the oxidase during phagocytosis of Staphylococcus aureus and Escherichia coli by mouse and human neutrophils, a mouse macrophage-like cell line and a human myeloid-like cell line. Phagocytosis of these bacteria was promoted by serum, independent of serum-derived antibodies, and effectively abolished in mouse neutrophils lacking the β2-integrin common chain, CD18. A combination of PI3K isoform-selective inhibitors, mouse knock-outs, and RNA-interference indicated CD18-dependent activation of the oxidase was independent of class I and II PI3Ks, but substantially dependent on the single class III isoform (Vps34). Class III PI3K was responsible for the synthesis of PtdIns(3)P on phagosomes containing either bacteria. The use of mouse neutrophils carrying an appropriate knock-in mutation indicated that PtdIns(3)P binding to the PX domain of their p40phox oxidase subunit is important for oxidase activation in response to both S aureus and E coli. This interaction does not, however, account for all the PI3K sensitivity of these responses, particularly the oxidase response to E coli, suggesting that additional mechanisms for PtdIns(3)P-regulation of the oxidase must exist.
Current differences in referral patterns for pulmonary endarterectomy in the UK
Authors: Toshner M. , Suntharalingam J. , Goldsmith K. , Niggebrugge A. , Pepke-Zaba J. , Morrell N. W. , Tsui S. , Flowers J. , Jenkins D. 
Published: August 2008

Pulmonary endarterectomy (PEA) surgery is the treatment of choice in surgically accessible chronic thromboembolic pulmonary hypertension and is potentially curative. The UK is served by seven specialist pulmonary hypertension centres and, consequently, there are regions which do not have a specialist unit. Since 2000, Papworth Hospital (Papworth Everard, UK) has been the sole PEA provider for the UK, offering the opportunity to study the national incidence of operable disease and give potential insight into factors that might affect geographical distribution within the UK.All 262 UK residents who underwent PEA surgery between April 2000 and May 2006 were included in the present study. The age-adjusted cumulative referral rates were compared between regions to test for uniformity.Overall, observed rates differed significantly from expected, with evidence of significant nonuniformity across the UK. The highest rates were observed in proximity to the nationally designated specialist centres and in particular in East Anglia and the West Midlands, nearest Papworth. These two regions differed by >2×sdfrom the national mean rate.The present study demonstrates wide geographical variation in the number of patients referred for pulmonary endarterectomy surgery. This suggests that there may be patients who are not presently being offered this potentially curative option.
Severity of obstructive sleep apnoea/hypopnoea syndrome and subsequent waking EEG spectral power
Authors: Grenèche J. , Sarémi M. , Erhardt C. , Hoeft A. , Eschenlauer A. , Muzet A. , Tassi P. 
Published: August 2008

It is well known that most patients with obstructive sleep apnoea/hypopnoea syndrome (OSAHS) suffer sleepiness, although the underlying mechanisms of this relationship remain unclear. The present study examined the relationship between nocturnal variables and the subsequent waking electroencephalogram (EEG), in order to determine if sleepiness was related to OSAHS severity and due to sleep fragmentation or to nocturnal hypoxaemia.In total, 12 moderate-to-severe OSAHS patients underwent a total sleep night followed by a 24-h period of sustained wakefulness where the waking EEG was measured every hour.The results showed that alpha (7.9–12.6 Hz) and beta (12.7–29.2 Hz) activities were strongly related to OSAHS severity, mainly reflected by the apnoea index. Moreover, spectral power in most of the waking EEG components was significantly correlated with nocturnal hypoxaemia indices, namely alpha and beta activity when hypoxaemia becomes severe. However, no correlation was found between the waking EEG and sleep fragmentation parameters.In conclusion, the present results suggest that the difficulty in maintaining an optimal level of alertness, reflected by a higher activity in awake alpha and beta bands (7.9–29.2 Hz) in obstructive sleep apnoea/hypopnoea syndrome, was better explained by: 1) the apnoea as opposed to the hypopnoea index; and 2) nocturnal hypoxaemia as opposed to sleep fragmentation.
Inhibition of airway proteases in cystic fibrosis lung disease
Authors: Griese M. , Kappler M. , Gaggar A. , Hartl D. 
Published: August 2008

Progressive lung disease determines the morbidity and mortality of cystic fibrosis (CF) patients.CF lung disease is characterised by endobronchial inflammation sustained by bacterial infections and an ongoing accumulation of airway neutrophils. Activated or necrotic neutrophils liberate proteases that cause damage to structural, cellular and soluble components of the pulmonary microenvironment.Among various proteases released by airway cells, elastase is considered to play the major role in CF lung disease. Based on this concept, several therapeutic approaches have been developed to inhibit free elastolytic activity, including small synthetic chemical compounds, semi-synthetic inhibitors and natural inhibitors of free elastase.The present review summarises and discusses the pathophysiological rationales, methodological requirements and clinical implications of inhibition of airway proteases in cystic fibrosis lung disease.
Short- and long-term response to corticosteroid therapy in chronic beryllium disease
Authors: Marchand-Adam S. , El Khatib A. , Guillon F. , Brauner M. W. , Lamberto C. , Lepage V. , Naccache J-M. , Valeyre D. 
Published: August 2008

Chronic beryllium disease (CBD) is a granulomatous disorder that affects the lung after exposure to beryllium. The present study reports short- and long-term evolution of granulomatous and fibrotic components in eight patients with severe CBD receiving corticosteroid therapy.Eight patients with confirmed CBD were studied at baseline, after initial corticosteroid treatment (4–12 months), at relapse and at the final visit. Beryllium exposure, Glu69(HLA-DPB1 genes coding for glutamate at position β69) polymorphism, symptoms, pulmonary function tests (PFT), serum angiotensin-converting enzyme (SACE) and high-resolution computed tomography (HRCT) quantification of pulmonary lesions were analysed.The CBD patients were observed for a median (range) of 69 (20–180) months. After stopping beryllium exposure, corticosteroids improved symptoms and PFT (vital capacity +26%, diffusing capacity of the lung for carbon monoxide +15%), and decreased SACE level and active lesion HRCT score. In total, 18 clinical relapses occurred after the treatment was tapered and these were associated with SACE and active lesion HRCT score impairment. At the final visit, corticosteroids had completely stabilised all parameters including both HRCT scores of active lesions and fibrotic lesions in six out of eight patients.Corticosteroids were beneficial in chronic beryllium disease. They were effective in suppressing granulomatosis lesions in all cases and in stopping the evolution to pulmonary fibrosis in six out of eight patients.
Modulation of cholinergic contractions of airway smooth muscle by cathinone: potential beneficial effects in airway diseases
Authors: Freund-Michel V. C. , Birrell M. A. , Patel H. J. , Murray-Lyon I. M. , Belvisi M. G. 
Published: August 2008

Infusion of khat leaves is an African traditional remedy used to treat airway diseases. The beneficial effects of khat are thought to be due to the activity of its main active component, cathinone.Cathinone inhibited electric field stimulation-induced acetylcholine release and the contractions of smooth muscle, which could be responsible for the beneficial effects seen in airway disease. The mechanism of action of this natural product appears to beviathe activation of both pre-junctional α2adrenergic and 5-hydroxytryptamine 7 receptors.The present novel study describes how cathinone modulates airway tone, and may go some way to explaining the traditional use of khat as a remedy for the alleviation of respiratory disease symptoms.In conclusion, cathinone may have beneficial effects in airway diseases with heightened cholinergic tone. There is some rationale for follow-up of these observations, given previous experience of other traditional remedies being developed for therapeutic use.