bluuebunny/crossref_metadata_2025_split huggingface dataset:
Occupational exposure to particulate air pollution and mortality due to ischaemic heart disease and cerebrovascular disease
Authors: Torén Kjell , Bergdahl Ingvar A , Nilsson Tohr , Järvholm Bengt 
Published: February 2007

Objectives:A growing number of epidemiological studies are showing that ambient exposure to particulate matter air pollution is a risk factor for cardiovascular disease; however, whether occupational exposure increases this risk is not clear. The aim of the present study was to examine whether occupational exposure to particulate air pollution increases the risk for ischaemic heart disease and cerebrovascular disease.Methods:The study population was a cohort of 176 309 occupationally exposed Swedish male construction workers and 71 778 unexposed male construction workers. The definition of exposure to inorganic dust (asbestos, man-made mineral fibres, dust from cement, concrete and quartz), wood dust, fumes (metal fumes, asphalt fumes and diesel exhaust) and gases and irritants (organic solvents and reactive chemicals) was based on a job-exposure matrix with focus on exposure in the mid-1970s. The cohort was followed from 1971 to 2002 with regard to mortality to ischaemic heart disease and cerebrovascular disease. Relative risks (RR) were obtained by the person-years method and from Poisson regression models adjusting for baseline values of blood pressure, body mass index, age and smoking habits.Results:Any occupational particulate air pollution was associated with an increased risk for ischemic heart disease (RR 1.13, 95% CI 1.07 to 1.19), but there was no increased risk for cerebrovascular disease (RR 0.97, 95% CI 0.88 to 1.07). There was an increased risk for ischaemic heart disease and exposure to inorganic dust (RR 1.07, 95% CI 1.03 to 1.12) and exposure to fumes (RR 1.05, 95% CI 1.00 to 1.10), especially diesel exhaust (RR 1.18, 95% CI 1.13 to 1.24). There was no significantly increased risk for cerebrovascular disease and exposure to inorganic dust, fumes or wood dust.Conclusions:Occupational exposure to particulate air pollution, especially diesel exhaust, among construction workers increases the risk for ischaemic heart disease.
Rhinitis and asthma symptoms in non-domestic cleaners from the São Paulo metropolitan area, Brazil
Authors: de Fátima Maçãira Elayne , Algranti Eduardo , Medina Coeli Mendonça Elizabete , Antônio Bussacos Marco 
Published: February 2007

Background:Exposure to cleaning products has frequently been reported as a symptom trigger by workers with work-related asthma diagnosed in workers’ health clinics in the city of São Paulo, Brazil.Objectives:To estimate rhinitis and asthma symptoms prevalence and to analyse associated risk factors.Method:A respiratory symptoms questionnaire (Medical Research Council 1976) and the International Study of Asthma and Allergies in Childhood questionnaire were applied to 341 cleaners working in the city of São Paulo, along with obtaining full occupational histories, skin prick tests and spirometry. Timing their symptoms onset in relation to occupational history allowed estimation of work-related asthma and/or rhinitis. Risk factors related to selected outcomes were analysed by logistic regression.Results:11% and 35% of the cleaners had asthma and rhinitis, respectively. The risk of work-related asthma/rhinitis increased with years of employment in non-domestic cleaning (OR 1.09, 95% CI 1.00 to 1.18, >0.92–3 years; OR 1.28, 95% CI 1.01 to 1.63, >3–6.5 years; OR 1.71, 95% CI 1.02 to 2.89, >6.5 years). Atopy was associated with asthma and rhinitis (OR 2.91, 95% CI 1.36 to 6.71; OR 2.06, 95% CI 1.28 to 3.35, respectively). There was a higher risk of rhinitis in women (OR 2.07, 95% CI 1.20 to 3.70).Conclusions:Cleaning workers are at risk of contracting work-related asthma and/or rhinitis, and the risk increases with years of employment in non-domestic cleaning. Women present higher risk of rhinitis than men.
The management of poor performance
Authors: Mayberry John F 
Published: February 2007

Abstract
Identification of poor performance is in an integral part of government policy. The suggested approach for the identification of such problems, advocated by the General Medical Council, is that of appraisal. However, traditionally, there has been a reluctance to deal with poor performers, as all doctors have made mistakes and are usually only too ready to forgive and be non-critical of colleagues. The problems are widespread, and 6% of the senior hospital workforce in any 5-year period may have problems.
Complete occlusion of extracranial internal carotid artery: clinical features, pathophysiology, diagnosis and management
Authors: Thanvi Bhomraj , Robinson Tom 
Published: February 2007

Abstract
A complete occlusion of the internal carotid artery (ICA) is an important cause of cerebrovascular disease. A never-symptomatic ICA occlusion has a relatively benign course, whereas symptomatic occlusion increases future risk of strokes. Ultrasonography, magnetic resonance imaging and contrast angiography are useful diagnostic tests, and functional imaging of the brain (eg, with positron emission tomography) helps to understand haemodynamic factors involved in the pathophysiology of brain ischaemia. Recently, there has been a resurgence of interest in the role of extracranial–intracranial bypass surgery for the treatment of completely occluded ICA. With advances in the measurement of cerebral haemodynamics, it may be possible to identify high-risk patients who could benefit from the bypass surgery.
Mycoplasma pneumoniae and its role in asthma
Authors: Nisar Nazima , Guleria Randeep , Kumar Sanjay , Chand Chawla Tirlok , Ranjan Biswas Nihar 
Published: February 2007

Abstract
Mycoplasma pneumoniae (M pneumoniae), primarily recognised as a causative agent of community-acquired pneumonia has recently been linked to asthma. An infection with M pneumoniae may precede the onset of asthma or exacerbate asthma symptoms. Chronic infection with M pneumoniae has been suspected to play a part in some patients with asthma. The role of immunoglobulin E-related hypersensitivity and induction of T helper type 2 immune response leading to inflammatory response in M pneumoniae-infected patients with asthma have also been proposed. Use of macrolides in reducing asthma symptoms only in M pneumoniae-infected patients supports the use of macrolides in patients with asthma having M pneumoniae infection. As macrolides are both antimicrobial and anti-inflammatory drugs, the therapeutic role of their biphasic nature in reducing asthma symptoms needs further attention in clinical research.
Impact of early biliary complications in liver transplantation in the presence or absence of a T-tube: a Chinese transplant centre experience
Authors: Li Tang , Chen Zhi-Shui , Zeng Fan-Jun , Ming Chang-Sheng , Zhang Wei-Jie , Liu Dun-Gui , Jiang Ji-Ping , Du Dun-Feng , Klaus Chen Zhong-Hua 
Published: February 2007

Abstract

Background
Biliary complications continue to be an important determinant of the recipient's survival rate after orthotopic liver transplantation (OLT). The objective of this study was to evaluate the incidence of early biliary complications in OLT in the presence or absence of a T-tube.

Methods
This retrospective study, based on inpatient data, focused on the relationship between T-tube placement and early biliary complications of 84 patients after OLT, from November 2002 to June 2005. Patients were divided into two groups based on whether or not a T-tube was used following bile duct reconstruction: T-tube group (group I, n = 33); non-T-tube group (group II, n = 51).

Results
45.2% of OLT recipients had a malignant neoplasm. There were no significant differences in the demographic characteristics or operation data between the two groups. Overall, early biliary tract complications developed in 19.0% (16/84) of patients. The rate of early biliary complications was 30.3% (10/33) and 11.8% (6/51) in groups I II, respectively (p = 0.035). Biliary complications which were directly caused by T-tube placement occurred in 12.1% (4/33) of patients in group I. Overall, the percentage of malignant neoplasms, chronic viral cirrhosis, fulminant liver failure and other primary disease recipients with early biliary complications were 6.2%, 37.5%, 43.8% and 12.5%, respectively.

Conclusion
This study suggests that the use of a T-tube in Chinese patients undergoing OLT causes a higher incidence of early biliary complications. Most of the early biliary complications occurred in chronic viral cirrhosis and fulminant liver failure recipients.
Dietary habits of young people attending secondary schools serving a multiethnic, inner-city community in the UK
Authors: Stone Margaret A , Bankart John , Sinfield Paul , Talbot Diane , Farooqi Azhar , Davies Melanie J , Khunti Kamlesh 
Published: February 2007

Abstract

Background
Childhood obesity is an escalating health concern with important implications, including increased risk of type 2 diabetes and cardiovascular disease. Although South Asians in the UK have an increased risk of developing these conditions, detailed studies on their lifestyles including the dietary habits of young people are scarce.

Methods
As part of an action research project, a food intake questionnaire was used to survey the dietary habits of 11–15-year olds attending five inner-city schools serving a predominantly South Asian population. Food choices were considered in the overall sample and in South Asians compared with white Europeans.

Results
3418 (72% of registered pupils) responses were obtained. A subset of 3018 pupils could be categorised as either South Asian (86%) or white European (14%). Around one fifth of pupils started the school day without eating anything. Responses indicated high consumption of “negative” foods such as sweets, including Asian sweets (63%), but lower rates for “positive” foods such as vegetables (34%). In the full sample, 26% said they had consumed more than one can of sugar-sweetened fizzy drink and 17% reported eating more than one packet of full-fat crisps on the previous day. Poor dietary habits were indicated in both South Asian and white European pupils.

Conclusions
Our large-scale survey confirmed poor dietary habits in secondary school pupils from a multiethnic community. Urgent efforts are needed to find ways of encouraging healthy lifestyles, particularly in populations with a high risk of developing cardiovascular disease and type 2 diabetes.
p38-Mediated Inactivation of Cyclin D1/Cyclin-Dependent Kinase 4 Stimulates Nucleolar Translocation of RelA and Apoptosis in Colorectal Cancer Cells
Authors: Thoms Hazel C. , Dunlop Malcolm G. , Stark Lesley A. 
Published: February 2007

Abstract
Aberrant nuclear factor-κB (NF-κB) signaling plays a role in cancer initiation and progression; thus, it represents a potential therapeutic target. We previously identified a mechanism of repression of NF-κB transcriptional activity and induction of apoptosis in colon cancer cells involving nuclear/nucleolar translocation of the RelA (p65) component of NF-κB. This response was stimulated by cellular stress-inducing agents, including aspirin, but not by tumor necrosis factor. Here, we investigate the upstream molecular mechanisms responsible for nucleolar targeting of RelA and show that aspirin activates the p38 mitogen-activated protein kinase (MAPK) pathway in colorectal cancer cells. We also show that aspirin causes rapid, ubiquitin-dependent degradation of cyclin D1, a known p38 target. Aspirin-induced p38 activation preceded cyclin D1 degradation, which was then followed by activation of the NF-κB pathway, suggesting a causative link. Indeed, chemical p38 inhibition (PD169316) and small interfering RNA directed against p38 blocked aspirin-induced cyclin D1 degradation, nucleolar translocation of RelA, and apoptosis. Furthermore, chemical inhibition of the cyclin D1/cyclin-dependent kinase 4 (CDK4) kinase complex, used as a surrogate for cyclin D1 degradation, caused nucleolar translocation of RelA, repression of κB-driven transcription, and apoptosis, thereby reproducing the effects of aspirin. In addition, we found that aspirin and the CDK4 inhibitor induced nucleolar translocation of RelA and apoptosis through a common mechanism involving the NH2-terminal nucleolar localization signal. Collectively, these data suggest that aspirin causes inhibition of cyclin D1/CDK4 through the p38 MAPK pathway. This inhibition stimulates the NF-κB pathway to induce nucleolar translocation of RelA and apoptosis. These novel findings have considerable relevance to the rational design of novel chemotherapeutic and chemopreventative strategies. [Cancer Res 2007;67(4):1660–9]
c-Met Overexpression Is a Prognostic Factor in Ovarian Cancer and an Effective Target for Inhibition of Peritoneal Dissemination and Invasion
Authors: Sawada Kenjiro , Radjabi A. Reza , Shinomiya Nariyoshi , Kistner Emily , Kenny Hilary , Becker Amy R. , Turkyilmaz Muge A. , Salgia Ravi , Yamada S. Diane , Vande Woude George F. , Tretiakova Maria S. , Lengyel Ernst 
Published: February 2007

Abstract
The hepatocyte growth factor receptor c-Met is a receptor tyrosine kinase that plays an important role in tumor growth by activating mitogenic signaling pathways. The goal of this study was to evaluate the role of c-Met in the biology of ovarian cancer and to determine its potential as a therapeutic target. c-Met protein expression was detected by immunohistochemistry in 138 advanced-stage ovarian cancers using a tissue microarray annotated with disease-specific patient follow-up. Fifteen of 138 (11%) tissues had c-Met overexpression. Median survival for patients with high c-Met levels was 17 months versus 32 months (P = 0.001) for patients with low c-Met expression. Infection of SKOV-3ip1 cells with an adenovirus expressing a small interfering RNA (siRNA) against c-Met efficiently inhibited c-Met protein and mRNA expression as well as extracellular signal-regulated kinase and phosphatidylinositol 3-kinase signaling. It also inhibited adhesion to different extracellular matrix components, human primary mesothelial cells, and full-thickness human peritoneum and, in vivo, to mouse peritoneum. This was paralleled by a significant reduction in α5 and β1 integrin protein and mRNA expression as well as a reduction of urokinase and matrix metalloproteinase (MMP)-2/MMP-9 activity. In SKOV-3ip1 ovarian cancer xenografts, i.p. treatment with the c-Met siRNA significantly reduced tumor burden, ascites formation, protease activity, and the number of peritoneal implants but not tumor size or angiogenesis. These results suggest that c-Met overexpression is a prognostic factor in ovarian cancer and that targeting c-Met in vivo inhibits peritoneal dissemination and invasion through an α5β1 integrin-dependent mechanism. Therefore, c-Met should be explored further as a therapeutic target in ovarian cancer. [Cancer Res 2007;67(4):1670–9]
Up-Regulation of c-Jun Inhibits Proliferation and Induces Apoptosis via Caspase-Triggered c-Abl Cleavage in Human Multiple Myeloma
Authors: Podar Klaus , Raab Marc S. , Tonon Giovanni , Sattler Martin , Barilà Daniela , Zhang Jing , Tai Yu-Tzu , Yasui Hiroshi , Raje Noopur , DePinho Ronald A. , Hideshima Teru , Chauhan Dharminder , Anderson Kenneth C. 
Published: February 2007

Abstract
Here we show the antimyeloma cytotoxicity of adaphostin and carried out expression profiling of adaphostin-treated multiple myeloma (MM) cells to identify its molecular targets. Surprisingly, c-Jun was the most up-regulated gene even at the earliest point of analysis (2 h). We also observed adaphostin-induced c-Abl cleavage in immunoblot analysis. Proteasome inhibitor bortezomib, but not melphalan or dexamethasone, induced similar effects, indicating unique agent-dependent mechanisms. Using caspase inhibitors, as well as caspase-resistant mutants of c-Abl (TM-c-Abl and D565A-Abl), we then showed that c-Abl cleavage in MM cells requires caspase activity. Importantly, both overexpression of the c-Abl fragment or c-Jun and knockdown of c-Abl and c-Jun expression by small interfering RNA confirmed that adaphostin-induced c-Jun up-regulation triggers downstream caspase-mediated c-Abl cleavage, inhibition of MM cell growth, and induction of apoptosis. Finally, our data suggest that this mechanism may not only be restricted to MM but may also be important in a broad range of malignancies including erythroleukemia and solid tumors. [Cancer Res 2007;67(4):1680–8]
A Src/Abl Kinase Inhibitor, SKI-606, Blocks Breast Cancer Invasion, Growth, and Metastasis In vitro and In vivo
Authors: Jallal Houda , Valentino Maria-Luisa , Chen Gaoping , Boschelli Frank , Ali Suhad , Rabbani Shafaat A. 
Published: February 2007

Abstract
The central role of Src in the development of several malignancies, including breast cancer, and the accumulating evidence of its interaction with receptor tyrosine kinases, integrins, and steroid receptors have identified it as an attractive therapeutic target. In the current study, we have evaluated the effect of a Src/Abl kinase inhibitor, SKI-606, on breast cancer growth, migration, invasion, and metastasis. Treatment of human breast cancer cells MDA-MB-231 with SKI-606 caused a marked inhibition of cell proliferation, invasion, and migration by inhibiting mitogen-activated protein kinase and Akt phosphorylation. For in vivo studies, MDA-MB-231 cells transfected with the plasmid encoding green fluorescent protein (GFP; MDA-MB-231-GFP) were inoculated into the mammary fat pads of female BALB/c nu/nu mice. Once tumor volume reached 30 to 50 mm3, animals were randomized and treated with vehicle alone or 150 mg/kg SKI-606 by daily oral gavage. Experimental animals receiving SKI-606 developed tumors of significantly smaller volume (45–54%) compared with control animals receiving vehicle alone. Analysis of lungs, liver, and spleen of these animals showed a significant decrease in GFP-positive tumor metastasis in animals receiving SKI-606 at a dose that was well tolerated. Western blot analysis and immunohistochemical analysis of primary tumors showed that these effects were due to the ability of SKI-606 to block tumor cell proliferation, angiogenesis, growth factor expression, and inhibition of Src-mediated signaling pathways in vivo. Together, the results from these studies provide compelling evidence for the role of Src inhibitors as therapeutic agents for blocking breast cancer growth and metastasis. [Cancer Res 2007;67(4):1580–8]
Aurora-A Regulation of Nuclear Factor-κB Signaling by Phosphorylation of IκBα
Authors: Briassouli Paraskevi , Chan Florence , Savage Kay , Reis-Filho Jorge S. , Linardopoulos Spiros 
Published: February 2007

Abstract
The Aurora-A/STK15 gene encodes a kinase that is frequently amplified in cancer. Overexpression of Aurora-A in mammalian cells leads to centrosome amplification, genetic instability, and transformation. In this study, we show that Aurora-A activates nuclear factor-κB (NF-κB) via IκBα phosphorylation. Inhibition of endogenous Aurora-A reduces tumor necrosis factor α (TNFα)–induced IκBα degradation. We analyzed primary human breast cancers, and 13.6% of samples showed Aurora-A gene amplification, all of which exhibited nuclear localization of NF-κB. We propose that this subgroup of patients with breast cancer might benefit from inhibiting Aurora-A. We also show that down-regulation of NF-κB via Aurora-A depletion can enhance cisplatin-dependent apoptosis. These data define a new role for Aurora-A in regulating IκBα that is critical for the activation of NF-κB–directed gene expression and may be partially responsible for the oncogenic effect of Aurora-A when the gene is amplified and overexpressed in human tumors. [Cancer Res 2007;67(4):1689–95]
c-Jun NH2-Terminal Kinase–Related Na+/H+ Exchanger Isoform 1 Activation Controls Hexokinase II Expression in Benzo(a)Pyrene-Induced Apoptosis
Authors: Huc Laurence , Tekpli Xavier , Holme Jørn A. , Rissel Mary , Solhaug Anita , Gardyn Claire , Le Moigne Gwénaelle , Gorria Morgane , Dimanche-Boitrel Marie-Thérèse , Lagadic-Gossmann Dominique 
Published: February 2007

AbstractRegulation of the balance between survival, proliferation, and apoptosis on carcinogenic polycyclic aromatic hydrocarbon (PAH) exposure is still poorly understood and more particularly the role of physiologic variables, including intracellular pH (pHi). Although the involvement of the ubiquitous pHi regulator Na+/H+ exchanger isoform 1 (NHE1) in tumorigenesis is well documented, less is known about its role and regulation during apoptosis. Our previous works have shown the primordial role of NHE1 in carcinogenic PAH-induced apoptosis. This alkalinizing transporter was activated by an early CYP1-dependent H2O2 production, subsequently promoting mitochondrial dysfunction leading to apoptosis. The aim of this study was to further elucidate how NHE1 was activated by benzo(a)pyrene (BaP) and what the downstream events were in the context of apoptosis. Our results indicate that the mitogen-activated protein kinase kinase 4/c-Jun NH2-terminal kinase (MKK4/JNK) pathway was a link between BaP-induced H2O2 production and NHE1 activation. This activation, in combination with BaP-induced phosphorylated p53, promoted mitochondrial superoxide anion production, supporting the existence of a common target for NHE1 and p53. Furthermore, we showed that the mitochondrial expression of glycolytic enzyme hexokinase II (HKII) was decreased following a combined action of NHE1 and p53 pathways, thereby enhancing the BaP-induced apoptosis. Taken together, our findings suggest that, on BaP exposure, MKK4/JNK targets NHE1 with consequences on HKII protein, which might thus be a key protein during carcinogenic PAH apoptosis. [Cancer Res 2007;67(4):1696–705]
Sphingosine-1-Phosphate Protects Proliferating Endothelial Cells from Ceramide-Induced Apoptosis but not from DNA Damage–Induced Mitotic Death
Authors: Bonnaud Stéphanie , Niaudet Colin , Pottier Géraldine , Gaugler Marie-Hélène , Millour Julie , Barbet Jacques , Sabatier Laure , Paris François 
Published: February 2007

AbstractBecause of the central role of the endothelium in tissue homeostasis, protecting the vasculature from radiation-induced death is a major concern in tissue radioprotection. Premitotic apoptosis and mitotic death are two prevalent cell death pathways induced by ionizing radiation. Endothelial cells undergo apoptosis after radiation through generation of the sphingolipid ceramide. However, if mitotic death is known as the established radiation-induced death pathway for cycling eukaryotic cells, direct involvement of mitotic death in proliferating endothelial radiosensitivity has not been clearly shown. In this study, we proved that proliferating human microvascular endothelial cells (HMEC-1) undergo two waves of death after exposure to 15 Gy radiation: an early premitotic apoptosis dependent on ceramide generation and a delayed DNA damage–induced mitotic death. The fact that sphingosine-1-phosphate (S1P), a ceramide antagonist, protects HMEC-1 only from membrane-dependent apoptosis but not from DNA damage–induced mitotic death proves the independence of the two pathways. Furthermore, adding nocodazole, a mitotic inhibitor, to S1P affected both cell death mechanisms and fully prevented radiation-induced death. If our results fit with the standard model in which S1P signaling inhibits ceramide-mediated apoptosis induced by antitumor treatments, such as radiotherapy, they exclude, for the first time, a significant role of S1P-induced molecular survival pathway against mitotic death. Discrimination between ceramide-mediated apoptosis and DNA damage–induced mitotic death may give the opportunity to define a new class of radioprotectors for normal tissues in which quiescent endothelium represents the most sensitive target, while excluding malignant tumor containing proproliferating angiogenic endothelial cells that are sensitive to mitotic death. [Cancer Res 2007;67(4):1803–11]