bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pilot study of MDR1 gene transfer into hematopoietic stem cells and chemoprotection in metastatic breast cancer patients
Authors: Takahashi Shunji , Aiba Keisuke , Ito Yoshinori , Hatake Kiyohiko , Nakane Minoru , Kobayashi Takayuki , Minowa Sayuri , Shibata Harumi , Mitsuhashi Junko , Tsukahara Satomi , Ishikawa Etsuko , Suzuki Rieko , Tsuruo Takashi , Sugimoto Yoshikazu 
Published: August 2007

A major problem in high‐dose chemotherapy with autologous hematopoietic stem cell transplantation is insufficient function of reconstituted bone marrow that limits the efficacy of post‐transplantation chemotherapy. Because transduction of hematopoietic stem cells with the multidrug resistance 1 (MDR1) gene might circumvent this problem, we conducted a pilot study of MDR1 gene therapy against metastatic breast cancer. Peripheral blood stem cells were harvested, and one‐third of the cells were transduced with MDR1 retrovirus. After the reconstitution of bone marrow function, the patients received high‐dose chemotherapy with transplantation of both MDR1‐transduced and unprocessed peripheral blood stem cells. The patients then received docetaxel chemotherapy. Two patients received transplantation of the MDR1‐transduced cells in 2001. Peripheral blood MDR1‐transduced leukocytes were 3–5% of the total cells after transplantation, but decreased gradually. During docetaxel chemotherapy, an increase in the rate of MDR1‐transduced leukocytes (up to 10%) was observed. Comparison of docetaxel‐induced granulocytopenia in the two patients suggested a bone marrow‐protective effect of the MDR1‐transduced cells. No serious side‐effect was observed, and the patients were in complete remission for more than 3 years. The MDR1‐transduced cells gradually decreased and disappeared almost entirely by the end of 2004. Results of linear amplification‐mediated polymerase chain reaction of the MDR1‐transduced leukocytes suggested no sign of abnormal amplification of the transduced cells. A third patient received transplantation of the MDR1‐transduced cells in 2004. These results suggest the feasibility of our MDR1 gene therapy against metastatic breast cancer, and follow‐up is ongoing. (Cancer Sci 2007; 98: 1609–1616)
Overexpression of CYP2A6 in human colorectal tumors
Authors: Matsuda Yoko , Saoo Kousuke , Yamakawa Keiko , Yokohira Masanao , Suzuki Satoshi , Kuno Toshiya , Kamataki Tetsuya , Imaida Katsumi 
Published: August 2007

CYP2A6 metabolizes various nitrosamines, such as those in the diet and in tobacco smoke, which have been implicated as risk factors for colorectal tumors. To determine whether changes in expression levels could contribute to their progression, we carried out immunohistochemistry for CYP2A6 in human colon tumors. Colon specimens (n = 53) were diagnosed as adenoma (n = 16), adenocarcinoma (n = 30) or carcinoma in or with adenoma (n = 7). Colon tumor cells showed cytoplasmic granular immunoreactivity for CYP2A6. Adenocarcinomas and adjacent mucosa showed similar highly elevated degrees of CYP2A6 expression, whereas carcinomas in or with adenoma and adenomas showed lesser increases. To further determine whether CYP2A6 mRNA was expressed at the same level as the CYP2A6 protein, we carried out in situ hybridization of CYP2A6 in two cases of adenocarcinoma. In situ hybridization for CYP2A6 revealed mRNA expression in adenocarcinoma cells. The data indicate that CYP2A6 may have important roles in human colorectal tumorigenesis and progression, so that it could be a candidate therapeutic and chemopreventive target for colorectal cancers. (Cancer Sci 2007; 98: 1582–1585)
Reduced transthyretin expression in sera of lung cancer
Authors: Liu Liyun , Liu Jifu , Dai Songwei , Wang Xiaomin , Wu Shanshan , Wang Jianing , Huang Lingyun , Xiao Xueyuan , He Dacheng 
Published: August 2007

Lung cancer is a leading cause of cancer death worldwide, and very few specific biomarkers can be used in its clinical diagnosis. Using surface‐enhanced laser desorption–ionization time‐of‐flight mass spectrometry (MS) to find novel serum biomarkers for lung cancer, we analyzed 227 serum samples, including 146 lung cancers, 41 benign lung diseases and 40 normal individuals. Three peaks, at 13.78, 13.90 and 14.07 k m/z, were significantly lower in lung cancer sera compared with sera from normal individuals (P < 0.001), whereas these peaks were higher than those in the sera of benign lung diseases (P < 0.001). The peaks were identified as native transthyretin (TTR) and its two variants by one‐dimensional polyacrylamide gel electrophoresis, ESI‐MS/MS, immunoprecipitation and western blot analysis. An enzyme‐linked immunosorbent assay indicated that TTR levels were consistent with surface‐enhanced laser desorption–ionization analysis in all groups tested. It gave 78.5% sensitivity and 77.5% specificity for lung cancer versus normal at the cut‐off point 115 µg/mL, and 66.7% sensitivity and 64.4% specificity for lung cancer versus benign lung diseases at the cut‐off point 88.5 µg/mL. Therefore, TTR may be useful as a biomarker to improve the diagnosis of lung cancer. (Cancer Sci 2007; 98: 1617–1624)
Advocacy for disabled children and young people: benefits and dilemmas
Authors: Knight Abigail , Oliver Chris 
Published: August 2007

ABSTRACTRecent policy has emphasized the need for advocacy services for children and young people, developments that have gone hand‐in‐hand with greater levels of participation of young people in decision‐making. Advocacy for disabled young people is especially important, as they are a particular vulnerable group and have, traditionally, been even more excluded from decisions about matters affecting their lives. This paper reports the findings, as they relate to disabled young people, from a study that investigated the role of advocacy for looked‐after children and children in need. The paper highlights some of the benefits of advocacy for disabled children, the dilemmas facing advocates between advocating and acting in someone's ‘best interests’, identifying the client and the boundaries between advocacy and social work. It argues that time given to establish a close relationship with a disabled child or young person is crucial if advocacy is to be effective and participation in decisions affecting their lives a reality.
Vascular endothelial cells and eosinophil infiltration in allergic rhinitis
Authors: Matsune S. , Ohori J. , Yosifuku K. , Kurono Y. 
Published: August 2007

SummaryEosinophils, as well as mast cells, play an important role in inducing the clinical symptoms of allergic rhinitis (AR), especially in the late‐phase response. Adhesion molecules, type 2 helper T (Th2) cell cytokines, CC chemokines, and eicosanoids from mast cells are key players of the pathophysiological mechanism of eosinophil transendothelial migration and accumulation in nasal mucosa. While tethering and adhesion of eosinophils to nasal microvascular endothelial cells are the critical steps, and adhesion molecules and their ligands expressed on eosinophils and endothelial cells have been well studied, regulation of these adhesion molecules and ligands by Th2 cytokines and CC chemokines is thought to be a very important mechanism of eosinophil migration. Eicosanoids such as cysteinyl leucotrienes (CysLTs) and thromboxanes (TXs) from mast cells are also considered to be major factors effective in the expression of adhesion molecules and their ligands, and eicosanoid receptors are thought to be distributed on nasal mucosal endothelial cells. For transendothelial migration, increasing vascular permeability is an indispensable step after trapping eosinophils in nasal microvasculature. While histamine is one of the best known vasodilators in AR, especially in the acute‐phase reaction, CysLTs and vascular endothelial growth factor (VEGF) are also effective vasodilators. Much of the evidence to date has been obtained using commercial cell lines of human umbilical vein endothelial cells (HUVEC), which may have cellular characteristics different from human nasal mucosal endothelial cells. Further studies of human nasal mucosa seem necessary to investigate the mechanisms of eosinophil recruitment in nasal mucosa of AR.
Possible role of prostaglandins in allergic inflammation
Authors: Nagai H. , Tanaka H. , Inagaki N. , Teramachi H. , Tsuchiya T. 
Published: August 2007

SummaryProstaglandins (PGs) and thromboxanes (TXs) are autacoids that exhibit a wide variety of actions in various cells and tissues. There is persuasive evidence that some PGs contribute to causing signs and symptoms of inflammation. In this study, we investigated the role of PGs and TXs in allergic airway inflammation by using a mouse model. When indomethacin was orally administered to allergic mice, the production of T‐helper type 2 cytokines, IgE antibody, and airway eosinophils and airway responsiveness to acetylcholine were accelerated. We next focused on the role of each PG by using mice lacking specific PG receptor genes. We examined the effects of depletion of PGD2 receptor (DP), PGE2 receptor (EP1, EP3, and EP4), PGI2 receptor (IP), and TxA2 receptor (TP) genes on the development of allergic inflammation in mice. As a result, allergic inflammation in the airway was accelerated in EP3 and IP gene knockout mice whereas inflammation was clearly suppressed in DP and TP gene‐deficient mice. These data suggest that PGE2 and PGI2 might have a suppressive role whereas PGD2 and TxA2 have pathological roles in the development of allergic airway inflammation.
In vivo and in vitro immunomodulation of Der p 1 allergen‐specific response by Lactobacillus plantarum bacteria
Authors: Hisbergues M. , Magi M. , Rigaux P. , Steuve J. , Garcia L. , Goudercourt D. , Pot B. , Pestel J. , Jacquet A. 
Published: August 2007

SummaryBackground
Lactic acid bacteria (LAB) were reported to reduce some allergic manifestations in mice and humans but their impact on the aeroallergen‐dependent immune mechanisms is still debated.Objective
The potential capacities of Lactobacillus plantarum NCIMB8826 to reduce the allergic response induced by Der p 1, the major house dust mite allergen of Dermatophagoides pteronyssinus, were evaluated in vivo and in vitro.Methods
First, the effect of the intranasal co‐administration of LAB and purified Der p 1 allergen before a sensitization protocol was evaluated. The allergen‐specific antibody and cellular responses as well as airway inflammation were measured. Second, the impact of LAB on the cytokine profile of spleens cells from Der p 1‐sensitized mice was assessed. Third, upon stimulation with LAB, the levels of cytokine produced by dendritic cells derived from the bone marrow (BMDCs) of wild‐type, Toll‐like receptor 2 (TLR2)‐, TLR4‐ and MyD88‐KO mice were compared.Results
The co‐application of L. plantarum and Der p 1 induced a T‐helper type 1 (Th1)‐biased allergen‐specific IgG response, the absence of specific IgE response and favoured the production of INF‐γ upon allergen re‐stimulation. Moreover, the previous LAB administration reduced the development of bronchoalveolar lavage eosinophilia usually induced by aerosol exposure. Additionally, the studied LAB strain was shown to modify in vitro the cytokine level produced by Der p 1‐sensitized spleen cells mainly towards a Th1 profile. Finally, L. plantarum stimulated high IL‐12 and moderate IL‐10 production in mouse BMDCs notably through the TLR2‐, MyD88‐dependent and TLR4‐independent pathway.Conclusion
In vivo co‐administration of probiotic LAB with Der p 1 might prevent the development of the mite allergic response. The probiotic L. plantarum was shown to display in vitro therapeutic potentials for the treatment of allergy and to trigger the immune system by a TLR2‐ and MyD88‐dependent signalling pathway.
Early predictors for developing allergic disease and asthma: examining separate steps in the ‘allergic march’
Authors: Almqvist C. , Li Q. , Britton W. J. , Kemp A. S. , Xuan W. , Tovey E. R. , Marks G. B. ,   for the CAPS team
Published: August 2007

SummaryBackground
Sensitization and symptoms of allergic disease are strongly correlated, but little is known about the early clinical precursors of the development of allergen sensitization in childhood. The aim of this study was to identify these predictors, and to examine separately the effect of early sensitization on subsequent wheeze, asthma, rhinitis and eczema.Methods
In the Childhood Asthma Prevention Study, children with a family history of asthma were assessed for allergen sensitization, total serum IgE, wheeze, asthma, eczema and rhinitis at ages 18 months and 5 years. To examine predictors, at 18 months, for subsequent sensitization, children who were non‐sensitized at 18 months and had data on sensitization at 5 years were investigated, n=375. To examine the predictors, at age 18 months, of subsequent onset of symptoms, children who did not have wheeze, asthma, eczema or rhinitis at 18 months were followed‐up at 5 years, n=177.Results
Among children who were non‐sensitized at age 18 months, the presence of eczema [adjusted relative risk (aRR), 1.67, 95% confidence interval (CI) 1.20–2.33], but not wheeze, asthma or rhinitis, was an independent predictor of the onset of sensitization by age 5 years. Among children who were asymptomatic at age 18 months, sensitization to any allergen at 18 months was an independent predictor for the presence of wheeze (aRR 2.41, 95% CI 1.28–4.55), asthma (aRR 4.66, 95% CI 1.88–11.54) and rhinitis (aRR 1.77, 95% CI 1.08–2.90), but not for the development of eczema (aRR 0.78, 95% CI 0.23–2.64) at 5 years.Conclusion
In non‐sensitized children, eczema, but not wheeze, asthma or rhinitis is a predictor for subsequent development of sensitization. This suggests that early childhood eczema, rather than wheeze and rhinitis, may promote subsequent allergen sensitization and raises the possibility that early management of eczema may reduce the prevalence of sensitization in children.
Regulation of German cockroach extract‐induced IL‐8 expression in human airway epithelial cells
Authors: Lee K. E. , Kim J. W. , Jeong K. Y. , Kim K. E. , Yong T. S. , Sohn M. H. 
Published: August 2007

SummaryBackground
Cockroaches have been known as a cause of respiratory allergies such as asthma. IL‐8 plays an integral role in the coordination and persistence of the inflammatory process in the chronic inflammation of the airways in asthma.Objective
We investigated the mechanism by which German cockroach extract (GCE) triggers IL‐8 release from human airway epithelial cells.Methods
Chemical inhibitors were pretreated before addition of GCE for promoter activity and protein synthesis of IL‐8. The Transcriptional activity of IL‐8 promoter was analysed by mutational, deletional anaylsis and electrophoretic mobility shift assay (EMSA).Results
Stimulation of H292 cells with GCE resulted in a time‐ and concentration‐dependent induction of IL‐8 transcription and protein synthesis. IL‐8 promoter deletion analysis indicated that position −132 to +41 was essential for GCE‐induced IL‐8 transcription, and mutants with substitutions in activator protein (AP)‐1, nuclear factor (NF)‐IL6 and NF‐κB‐binding sites revealed a requirement for NF‐κB and NF‐IL6, but not AP‐1, in GCE‐induced activation of the IL‐8 promoter. The DNA‐binding activities of NF‐κB and NF‐IL6 were induced by GCE, as determined by EMSA. The chemical inhibition of extracellular signal‐regulated kinase (ERK) attenuated GCE‐induced transcriptional activity and protein synthesis. In addition, through aprotinin treatment and PAR2 small interfering RNA transfection, it was proven that protease of GCE is consistent with the regulation of GCE‐induced IL‐8.Conclusion
We conclude that GCE with protease activity‐induced IL‐8 expression is regulated by transcriptional activation of NF‐κB and NF‐IL6 coordinating with the ERK pathway in human airway epithelial cells.
Association between candidate genes and lung function growth in Chinese asthmatic children
Authors: Leung T. F. , Chan I. H. S. , Wong G. W. K. , Li C. Y. , Tang N. L. S. , Yung E. , Lam C. W. K. 
Published: August 2007

SummaryBackground
Asthma is caused by a complex interaction between multiple candidate genes and environmental factors. The Childhood Asthma Management Program reported lung function decline in a significant proportion of Caucasian asthmatic children, but such a relation has not been studied in other populations. Our group recently reported that interleukin‐13 (IL13), interleukin‐4 receptor‐α and thymus and the activation‐regulated chemokine interacted to influence asthma and raised plasma total IgE. However, there has not been any study that has addressed the genetic influences for longitudinal lung function growth.Objective
We studied the longitudinal changes in spirometric variables in Chinese asthmatic children, and investigated the influence and interactions between eight different loci in six candidate genes as well as environmental factors affecting lung function growth in these children.Methods
Spirometry was performed at baseline and study completion. Genotyping was performed by restriction fragment length polymorphism. Multi‐factor dimensionality reduction (MDR) was used to detect any gene–gene or gene–environment interaction.Results
We prospectively followed 131 Chinese children, aged 9.9 (3.0) years, for 4.5 (0.8) years. Their mean (standard deviation) baseline forced expiratory volume in 1 s (FEV1) was 98.6 (20.6)% of predicted, and FEV1 to forced vital capacity (FVC) ratio was 77.8 (11.3)%. FEV1 and FVC increased by 210 (115) and 248 (148) mL/year during this study, and these changes were significantly larger among males (P<0.0001). Univariate analysis revealed a significant association between annual FEV1 change and C1570T of signal transducer and activator of transcription 6 gene (STAT6; P=0.009). Linear regression confirmed this finding (P=0.041). Using MDR, we detected a significant 3‐locus interaction between IL13 R130Q, ADRB2 R16G and STAT6 C1570T for determining change in FVC (P=0.045).Conclusion
Our data suggest that STAT6 may influence lung function growth in asthmatic children. We also found significant interactions among several atopy‐related genetic polymorphisms for influencing FVC change.
Serum fasting cortisol in relation to bone, and the role of genetic variations in the glucocorticoid receptor
Authors: Van Schoor N. M. , Dennison E. , Lips P. , Uitterlinden A. G. , Cooper C. 
Published: August 2007

SummaryObjective  To examine the relationship between endogenous cortisol and bone, and the role of genetic variations in the glucocorticoid receptor (GR).Design and patients  The Longitudinal Ageing Study Amsterdam (LASA), a population‐based cohort study in older men and women.Measurements  Serum fasting cortisol was assessed by competitive immunoassay (n = 1214); bone mineral density (BMD) by dual X‐ray absorptiometry (DXA) (n = 502); broadband ultrasound attenuation (BUA) by ultrasound (n = 1209); fractures by self‐report (n = 1211); and GR gene polymorphisms (ER22/23EK, N363S, 9beta, BclI) were genotyped by Taqman (n = 858).Results  Higher serum fasting cortisol was significantly associated with lower BMD at all sites and BUA at the heel in women, although most relationships were attenuated by age and body mass index (BMI). The effect on femoral neck BMD remained statistically significant in the fully adjusted model (r = –0·135, P = 0·04). No significant associations in men were found. Female 9beta G‐allele carriers had 50·2 nmol/l lower cortisol and 1·2 lower free cortisol levels than AA homozygotes [P = 0·01 for (free) cortisol]. Furthermore, female BclI GG homozygotes had 54·8 nmol/l higher cortisol levels than C‐carriers (P = 0·03). In the total population, BclI GG homozygotes had 0·05 g/cm2 lower trochanteric region BMD (P = 0·03). For the other GR gene polymorphisms, no significant associations were found.Conclusions  Higher cortisol levels are associated with lower femoral neck BMD in elderly women. The G allele of the 9beta polymorphism was associated with lower serum cortisol levels in women. Female BclI GG homozygotes had higher serum cortisol levels, and BclI GG homozygotes had lower trochanteric region BMD in the total population.
Factors associated with elevated serum concentrations of anti‐TPO antibodies in subjects with and without diffuse goitre. Results from the Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident
Authors: McConnell Robert J. , Brenner Alina V. , Oliynyk Valery A. , Robbins Jacob , Terekhova Galyna M. , Fink Daniel J. , Epshtein Ovsiy V. , Hatch Maureen , Shpak Victor M. , Brill A. Bertrand , Shelkovoy Yevgeniy A. , Zablotska Lydia B. , Masnyk Ihor J. , Howe Geoffrey R. , Tronko Mykola D. 
Published: August 2007

SummaryObjectives  To examine factors associated with the prevalence of elevated anti‐thyroid peroxidase antibodies (ATPO) among iodine‐deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre.Design  Subjects were members of the Ukrainian–American Cohort Study exposed to the Chornobyl accident whose 131I thyroid dose estimates were below 0·2 Gy.Measurements  The odds ratios (ORs) for ATPO above 60 U/ml were estimated using logistic regression models for a number of factors in the total population (N = 5133), and separately for thyroid disease‐free subjects (N = 3875), those with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis (AIT; N = 883).Results  Elevated ATPO was found in 9·9% of the total population and ORs were significantly higher in females, older individuals, those examined in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with a family history of thyroid disease, higher thyroid ultrasound volume, suppressed or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg), and shorter serum storage time. When thyroid disease‐free subjects and those with diffuse goitre were compared, there were few differences in antibody prevalence, and after excluding individuals with AIT, the only difference was an increased prevalence of elevated ATPO at low urinary iodine in those with goitre alone.Conclusions  Although a number of factors are associated with the prevalence of elevated ATPO in our study group, with the exception of urinary iodine these factors are independent of goitre, and differences between thyroid disease‐free subjects and those with diffuse goitre are largely due to AIT.