bluuebunny/crossref_metadata_2025 huggingface dataset:
Angiography‐negative primary central nervous system vasculitis in children: A newly recognized inflammatory central nervous system disease
Authors: Benseler Susanne M. , deVeber Gabrielle , Hawkins Cynthia , Schneider Rayfel , Tyrrell Pascal N. , Aviv Richard I. , Armstrong Derek , Laxer Ronald M. , Silverman Earl D.
Published: June 2005

Inflammatory central nervous system (CNS) diseases in childhood comprise a wide spectrum of heterogeneous conditions. We studied 4 children with primary CNS vasculitis in whom results of magnetic resonance imaging studies were abnormal but results of conventional angiography were normal. We determined that angiography‐negative, biopsy‐confirmed primary small‐vessel CNS vasculitis is a previously unrecognized distinct disease entity in children. The diagnosis must be considered in a child with a progressive, acquired diffuse or focal neurologic deficit, even if the results of conventional angiography are normal. A lesional brain biopsy is required to confirm the diagnosis. Use of immunosuppressive therapy plus aspirin leads to an excellent neurologic outcome.
Tumor necrosis factor α blockade treatment down‐modulates the increased systemic and local expression of toll‐like receptor 2 and toll‐like receptor 4 in spondylarthropathy
Authors: De Rycke Leen , Vandooren Bernard , Kruithof Elli , De Keyser Filip , Veys Eric M. , Baeten Dominique
Published: June 2005

Objective

Abnormal host defense against pathogens has been implicated in the pathogenesis of spondylarthropathy (SpA), a disease characterized by abundant synovial infiltration with innate immune cells. Given the role of Toll‐like receptors (TLRs) in activation of innate inflammation and the occurrence of TLR‐dependent infections after tumor necrosis factor α (TNFα) blockade treatment, the present study was undertaken to analyze TLRs and their modulation by TNFα blockade in SpA.

Methods

Peripheral blood mononuclear cells (PBMCs) were obtained from SpA and rheumatoid arthritis (RA) patients during infliximab therapy, and from healthy controls. TLR‐2 and TLR‐4 expression and TNFα production upon lipopolysaccharide (LPS) stimulation were analyzed by flow cytometry on different monocyte subsets. Synovial biopsy specimens from 23 SpA patients before and after infliximab or etanercept treatment, from 15 RA patients, and from 18 osteoarthritis (OA) patients were analyzed by immunohistochemistry.

Results

Expression of TLR‐4, but not TLR‐2, was increased on PBMCs from patients with SpA, whereas both TLRs were increased in RA patients. TLR expression was particularly increased on the CD163+ macrophage subset. Infliximab reduced TLR‐2 and TLR‐4 expression on monocytes of SpA and RA patients, leading to lower levels than in controls and to impaired TNFα production upon LPS stimulation. In inflamed synovium, the expression of both TLRs and of CD163 was significantly higher in patients with SpA than in those with RA or OA. Paralleling the systemic effect, TLRs in synovium were down‐regulated following treatment with infliximab as well as etanercept, indicating a class effect of TNFα blockers.

Conclusion

Inflammation in SpA is characterized by increased TLR‐2 and TLR‐4 expression, which is sharply reduced by TNFα blockade. These findings suggest a potential role of innate immunity–mediated inflammation in SpA and provide an additional clue regarding the mechanism of action as well as the potential side effects of TNFα blockade.
Effective treatment of collagen‐induced arthritis by adoptive transfer of CD25+ regulatory T cells
Authors: Morgan Mary E. , Flierman Roelof , van Duivenvoorde Leonie M. , Witteveen Hendrik J. , van Ewijk Willem , van Laar Jacob M. , de vries René R. P. , Toes René E. M.
Published: June 2005

Objective

Regulatory T cells play an important role in the prevention of autoimmunity and have been shown to be effective in the treatment of experimental colitis, a T cell–mediated and organ‐specific disease. We previously demonstrated that intrinsic CD25+ regulatory T cells modulate the severity of collagen‐induced arthritis (CIA), which, in contrast to colitis, is a systemic antibody‐mediated disease and an accepted model of rheumatoid arthritis. We undertook this study to determine whether regulatory T cells have the potential to be used therapeutically in arthritis.

Methods

We transferred CD4+,CD25+ T cells into mice exhibiting arthritis symptoms, both immunocompetent mice and mice subjected to lethal irradiation and rescued with syngeneic bone marrow transplantation.

Results

A single transfer of regulatory T cells markedly slowed disease progression, which could not be attributed to losses of systemic type II collagen–specific T and B cell responses, since these remained unchanged after adoptive transfer. However, regulatory T cells could be found in the inflamed synovium soon after transfer, indicating that regulation may occur locally in the joint.

Conclusion

Our data indicate that CD25+ regulatory T cells can be used for the treatment of systemic, antibody‐mediated autoimmune diseases, such as CIA.
Host limits to accurate human growth hormone production in multiple plant systems
Authors: Russell Douglas A. , Spatola Lori A. , Dian Titik , Paradkar Vikram M. , Dufield Dawn R. , Carroll James A. , Schlittler Michael R.
Published: June 2005

The original article to which this Erratum refers was published in Biotechnol Bioeng 2005;89:775–782
[CH3MoF], [CH2MoHF], and [CHMoH2F] Formed by Reaction of Laser‐Ablated Molybdenum Atoms with Methyl Fluoride: Persistent Photoreversible Interconversion through α‐Hydrogen Migration and Agostic Interaction
Authors: Cho Han‐Gook , Andrews Lester
Published: June 2005

Simple molybdenum methyl, carbene, and carbyne complexes, [CH3MoF], [CH2MoHF], and [CHMoH2F], were formed by the reaction of laser‐ablated molybdenum atoms with methyl fluoride and isolated in an argon matrix. These molecules provide a persistent photoreversible system through α‐hydrogen migration between the carbon and metal atoms: The methyl and carbene complexes are produced by applying UV irradiation (240–380 nm) while the carbyne complex is depleted, and the process reverses on irradiation with visible light (λ>420 nm). An absorption at 589.3 cm−1 is attributed to the MoF stretching mode of [CH3MoF], which is in fact the most stable of the plausible products. Density functional theory calculations show that one of the α‐hydrogen atoms of the carbene complex is considerably bent toward the metal atom (∢HCMo=84.5°), which provides evidence of a strong agostic interaction in the triplet ground state. The calculated CMo bond length in the carbyne is in the range of triple‐bond values in methylidyne complexes.
Percutaneous biopsy of pediatric solid tumors
Authors: Garrett Kevin M. , Fuller Christine E. , Santana Victor M. , Shochat Stephen J. , Hoffer Fredric A.
Published: June 2005

BACKGROUND

The objective of the current study was to determine the diagnostic accuracy of percutaneous biopsy of pediatric solid tumors, a procedure that is less invasive than open biopsy.

METHODS

The authors conducted a retrospective analysis of clinical data related to 202 percutaneous core‐needle biopsies of solid tumors at St. Jude Children's Research Hospital over 5.5 years (from 1997 to 2003). In 103 patients, the procedure was performed to establish an initial diagnosis of a suspected malignancy; and, in 99 patients, disease recurrence was suspected. Biopsies were guided by ultrasound, computed tomography, or fluoroscopic imaging. From each tumor, 1–17 core biopsy samples (median, 6 samples) were obtained; the median needle size was 15 gauge (range, 13–20 gauge). The specimens were submitted for histopathologic analysis and other ancillary procedures (molecular pathology and/or cytogenetic analyses). The accuracy of the diagnoses from the biopsies was determined by subsequent surgery with or without pathologic assessment or by outcome.

RESULTS

When the biopsy samples were assessed for the presence of malignancy, there were 121 true‐positive results (90% sensitivity), 67 true‐negative results (100% specificity), and 14 false‐negative results (93% accuracy). In 103 tumors, when the procedure was performed for initial diagnosis, percutaneous needle biopsy showed a sensitivity of 97%, a specificity of 100%, and an accuracy of 98%. The 99 procedures for suspected recurrence were less reliable (sensitivity, 83%; specificity, 100%; accuracy, 88%).

CONCLUSIONS

Image‐guided percutaneous biopsy was highly accurate and safe in the diagnosis of pediatric malignant solid tumors. This technique may be able to supplant diagnostic open biopsy. Cancer 2005. © 2005 American Cancer Society.
Predictors and outcomes of surgeons' referral of older breast cancer patients to medical oncologists
Authors: Thwin Soe Soe , Fink Aliza K. , Lash Timothy L. , Silliman Rebecca A.
Published: June 2005

BACKGROUND

Older women are less likely than younger women to receive definitive care for a new diagnosis of breast cancer, but the reasons are not well understood. Although coordination of referral among specialists is an important component of quality of care, it has not been studied as a factor that contributes to observed age‐related variations in breast cancer care.

METHODS

Treatment recommendations by 191 surgeons of 559 patients aged ≥ 65 years with Stage I to IIIa breast cancer provided patient‐specific assessments of comorbidity and medical oncologist referral. Demographic, tumor, and treatment characteristics from medical records and telephone interviews were evaluated by statistical regression methods to identify factors associated with referral to a medical oncologist and to evaluate whether a referral resulted in discussion and prescription of tamoxifen.

RESULTS

Estrogen receptor protein negativity and higher tumor stage increased the likelihood of referral (odds ratio [OR] = 5.6, 95% confidence interval [CI] = 1.9–16.7, and OR = 4.2, 95% CI = 1.7–10.3, respectively), whereas a moderate to severely ill health status decreased the likelihood of referral (OR = 0.4, 95% CI = 0.2–0.9). Those referred were twice as likely to report having a discussion about tamoxifen (OR = 2.0, 95% CI = 1.06–3.7) and to have been prescribed tamoxifen (OR = 2.1, 95% CI = 0.99–4.3).

CONCLUSIONS

Referral to medical oncologists is associated with receipt of adjuvant tamoxifen therapy. The current study findings suggest that more consistent referral of older women to medical oncologists may enhance quality of discussion and participation in decisions concerning treatment options. Cancer 2005. © 2005 American Cancer Society.
Neuropeptide Y in the forebrain of the adult male cichlid fish Oreochromis mossambicus: Distribution, effects of castration and testosterone replacement
Authors: Sakharkar Amul J. , Singru Praful S. , Sarkar Koustav , Subhedar Nishikant K.
Published: June 2005

We studied the organization of the neuropeptide Y (NPY)‐immunoreactive system in the forebrain of adult male cichlid fish Oreochromis mossambicus and its response to castration and testosterone replacement by using morphometric methods. Immunoreactivity for NPY was widely distributed in the forebrain, and the pattern generally resembled that in other teleosts. Whereas immunoreactivity was conspicuous in the ganglia of nervus terminalis (NT; or nucleus olfactoretinalis), a weak reaction was detected in some granule cells in the olfactory bulb and in the cells of area ventralis telencephali pars lateralis (Vl). Moderately to intensely immunoreactive cells were distinctly seen in the nucleus entopeduncularis (NE), nucleus preopticus (NPO), nucleus lateralis tuberis (NLT), paraventricular organ (PVO), and midbrain tegmentum (MT). NPY fibers were widely distributed in the forebrain. Castration for 10/15 days resulted in a drastic loss of immunoreactivity in the cells of NE (P < 0.001) and a significant decrease (P < 0.01) in their cell nuclear size. However, cell nuclei of the NT neurons showed a significant increase in size. A highly significant reduction in the NPY‐immunoreactive fiber density (P < 0.001) was observed in several areas of the forebrain. Although testosterone replacement reversed these changes, fibers in some areas showed supranormal responses. Immunoreactive cells in Vl, NPO, NLT, PVO, and MT and fiber density in some other areas did not respond to castration. We suggest that the NPY‐immunoreactive elements that respond to castration and testosterone replacement may serve as the substrate for processing the positive feedback action of the steroid hormone. J. Comp. Neurol. 489:148–165, 2005. © 2005 Wiley‐Liss, Inc.
Developmental expression and comparative genomic analysis of Xenopus cardiac myosin heavy chain genes
Authors: Garriock Robert J. , Meadows Stryder M. , Krieg Paul A.
Published: June 2005

Myosin heavy chains (MHC) are cytoskeletal motor proteins essential to the process of muscle contraction. We have determined the complete sequences of the Xenopus cardiac MHC genes, α‐MHC and ventricular MHC (vMHC), and have characterized their developmental expression profiles. Whereas α‐MHC is expressed from the earliest stages of cardiac differentiation, vMHC transcripts are not detected until the heart has undergone chamber formation. Early expression of vMHC appears to mark the cardiac conduction system, but expression expands to include the ventricle and outflow tract myocardium during subsequent development. Sequence comparisons, transgenic expression analysis, and comparative genomic studies indicate that Xenopus α‐MHC is the true orthologue of the mammalian α‐MHC gene. On the other hand, we show that the Xenopus vMHC gene is most closely related to chicken ventricular MHC (vMHC1) not the mammalian β‐MHC. Comparative genomic analysis has allowed the detection of a mammalian MHC gene (MyH15) that appears to be the orthologue of vMHC, but evidence suggests that this gene is no longer active. Developmental Dynamics 233:1287–1293, 2005. © 2005 Wiley‐Liss, Inc.
Reference guide to the stages of chick heart embryology
Authors: Martinsen Brad J.
Published: June 2005

Cardiac progenitors of the splanchnic mesoderm (primary and secondary heart field), cardiac neural crest, and the proepicardium are the major embryonic contributors to chick heart development. Their contribution to cardiac development occurs with precise timing and regulation during such processes as primary heart tube fusion, cardiac looping and accretion, cardiac septation, and the development of the coronary vasculature. Heart development is even more complex if one follows the development of the cardiac innervation, cardiac pacemaking and conduction system, endocardial cushions, valves, and even the importance of apoptosis for proper cardiac formation. This review is meant to provide a reference guide (Table 1) on the developmental timing according to the staging of Hamburger and Hamilton (1951) (HH) of these important topics in heart development for those individuals new to a chick heart research laboratory. Even individuals outside of the heart field, who are working on a gene that is also expressed in the heart, will gain information on what to look for during chick heart development. This reference guide provides complete and easy reference to the stages involved in heart development, as well as a global perspective of how these cardiac developmental events overlap temporally and spatially, making it a good bench top companion to the many recently written in‐depth cardiac reviews of the molecular aspects of cardiac development. Developmental Dynamics 233:1217–1237, 2005. © 2005 Wiley‐Liss, Inc.
Synthesis of Alkaloid Analogues from α‐Amino Acids by One‐Pot Radical Decarboxylation/Alkylation
Authors: Boto Alicia , De León Yolanda , Gallardo Juan Antonio , Hernández Rosendo
Published: June 2005

A mild, one‐pot methodology to obtain α‐substituted nitrogen heterocycles from commercial amino acids is reported. This versatile procedure has been applied to the synthesis of different alkaloid analogues in good to excellent yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Selective Synthesis and Cycloaddition Reactions of New Azomethine Imines Containing a 1,2,4‐Triazine Ring
Authors: Gróf Csilla , Hegedűs Gábor , Riedl Zsuzsanna , Hajós György , Egyed Orsolya , Csámpai Antal , Kudar Veronika , Stanovnik Branko
Published: June 2005

The reactions of 4,5‐dihydro[1,2,4]triazolo[3,4‐c]benzo[1,2,4]triazines with aromatic aldehydes gave stable iminium salts which were deprotonated to give new azomethine imines. These new mesomeric betaines underwent 1,3‐dipolar cyclization reactions to yield new tetra‐ and pentacyclic heterocycles. X‐ray analysis and decoupling NMR experiments unambiguously supported the fact that these transformations are regioselective and that the iminium moieties were formed at the N‐5 atom in each case. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Factor forecasts for the UK
Authors: Artis Michael J. , Banerjee Anindya , Marcellino Massimiliano
Published: June 2005

Data are now readily available for a very large number of macroeconomic variables that are potentially useful when forecasting. We argue that recent developments in the theory of dynamic factor models enable such large data sets to be summarized by relatively few estimated factors, which can then be used to improve forecast accuracy. In this paper we construct a large macroeconomic data set for the UK, with about 80 variables, model it using a dynamic factor model, and compare the resulting forecasts with those from a set of standard time‐series models. We find that just six factors are sufficient to explain 50% of the variability of all the variables in the data set. These factors, which can be shown to be related to key variables in the economy, and their use leads to considerable improvements upon standard time‐series benchmarks in terms of forecasting performance. Copyright © 2005 John Wiley & Sons, Ltd.
Expression levels of the putative zinc transporter LIV‐1 are associated with a better outcome of breast cancer patients
Authors: Kasper Grit , Weiser Armin A. , Rump Andreas , Sparbier Katrin , Dahl Edgar , Hartmann Arndt , Wild Peter , Schwidetzky Uta , Castaños‐Vélez Esmeralda , Lehmann Kerstin
Published: June 2005

We investigated the expression pattern of the breast cancer associated gene LIV‐1 on mRNA and protein level in 111 human breast cancer patients by in situ hybridization as well as immunohistochemistry and focused on the unknown potential of LIV‐1 expression levels as a prognostic marker. To our knowledge, this is the first study on endogenous LIV‐1 protein expression. Results of our study indicate that LIV‐1 mRNA and protein expression levels are only weakly correlated, suggesting posttranscriptional regulatory mechanisms. Furthermore, LIV‐1 mRNA quantity in combination with a positive ER status seem to represent a better marker than the progesterone receptor status according to the prognostic significance for relapse free survival (RFS). A negative correlation of LIV‐1 protein levels with tumor size, grade and stage reflects an association of LIV‐1 protein expression with less aggressive tumors. High LIV‐1 protein expression seems to be associated with a longer relapse free and overall survival in breast cancer patients with invasive ductal carcinoma. This association, however, seems to be dependent from other prognostic markers. Our data suggest that LIV‐1 is a promising candidate for a novel marker for breast cancer patients with better outcome. Furthermore, our study presents a revised cDNA sequence of LIV‐1 and demonstrates the localization of endogenous LIV‐1 in the endoplasmic reticulum. (Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience. wiley.com/jpages/0020‐7136/suppmat/index.html). © 2005 Wiley‐Liss, Inc.
High‐throughput tissue microarray analysis of CMYC amplificationin urinary bladder cancer
Authors: Zaharieva Boriana , Simon Ronald , Ruiz Christian , Oeggerli Martin , Mihatsch Michael J. , Gasser Thomas , Sauter Guido , Toncheva Draga
Published: June 2005

Alterations of chromosome 8, preferentially deletions of 8p and gains of 8q, belong to the most frequent cytogenetic changes in bladder cancer. CMYC on 8q24 is a candidate oncogene in this region. Little is known about the clinical significance of CMYC copy number changes in urinary bladder cancer because its frequency is low and a limited numbers of tumors were analyzed so far. To investigate the impact of CMYC alterations on tumor progression and patient prognosis in bladder cancer, we applied FISH to a tissue microarray containing 2317 bladder cancer samples. Presence of CMYC copy number increase was associated with advanced stage and high grade. CMYC amplifications were seen in 3 of 467 pTa (0.6%), 10 of 247 pT1 (4%) and 11 of 201 pT2–4 urothelial carcinomas (5.5%; p < 0.0001), as well as in 1 of 123 G1 (0.8%), 8 of 470 G2 (1.7%) and 17 of 365 G3 urothelial carcinomas (4.7%; p < 0.0001). CMYC gains were present in 49 of 467 pTa (10.5%), 39 of 247 pT1 (15.8%) and 43 of 201 pT2–4 urothelial carcinoma (21.4%; p < 0.0001), as well as in 7 of 123 G1 (5.7%), 56 of 470 G2 (11.9%) and 72 of 365 G3 urothelial carcinomas (19.7%; p < 0.0001). CMYC copy number changes were unrelated to prognosis of bladder cancer patients. We conclude that alterations of the CMYC gene, including copy number gains and amplifications, are linked to genetically unstable bladder cancers that are characterized by a high histologic grade and/or invasive growth. Patient prognosis was not affected by CMYC gene copy number changes. © 2005 Wiley‐Liss, Inc.
Overexpression of the small transmembrane and glycosylated protein SMAGP supports metastasis formation of a rat pancreatic adenocarcinoma line
Authors: Tarbé Nesrine G. , Rio Marie‐Christine , Hummel Susanne , Weidle Ulrich H. , Zöller Margot
Published: June 2005

Small cell transmembrane and glycosylated protein (SMAGP) was recently identified in the metastasizing rat pancreatic adenocarcinoma line BSp73ASML. SMAGP, an evolutionary conserved transmembrane protein, is expressed on lateral epithelial cell membranes. SMAGP expression was restricted to or was upregulated in several metastasizing as compared to nonmetastasizing human and rat tumor lines. In contrast to nontransformed tissue, SMAGP was mainly expressed in the cytoplasm, as has already been described for high‐grade human colorectal cancer. This raised the question on the impact of SMAGP on tumor progression. To answer the question, metastasis formation was evaluated in the nonmetastasizing rat pancreatic adenocarcinoma subline BSp73AS (AS), which was stably transfected with SMAGP cDNA (AS‐SMAGP). Cytoplasmic SMAGP expression promoted cell agglomeration, but inhibited tumor cell proliferation, adhesion to and migration toward vitronectin and matrigel invasion, which was accompanied by a failure of actin reorganization. AS‐SMAGP clones strongly promoted metastasis formation by dislodgment of normal tissue; 82% of rats developed lymph node metastasis as compared to 22% of rats receiving AS or mock‐cDNA‐transfected AS cells. The incidence of lung metastasis was increased from 6% in AS to 98% in AS‐SMAGP tumor‐bearing rats. Thus, SMAGP strongly promotes tumor progression. This likely is due to redistribution from the plasma membrane into the cytoplasm. SMAGP redistribution does not only facilitate tumor cell detachment from neighboring cells and the extracellular matrix, but obviously contributes actively by a not yet defined mechanism to tumor cell agglomeration and capillary plugging. © 2005 Wiley‐Liss, Inc.
Ribozyme‐targeting reveals the rate‐limiting role of pleiotrophin in glioblastoma
Authors: Grzelinski Marius , Bader Nicole , Czubayko Frank , Aigner Achim
Published: June 2005

Glioblastomas (GBMs) are the most frequent malignant brain tumors with very limited treatment options and nearly all GBM patients dying within 1 year. Pleiotrophin (PTN, HB‐GAM, HBNF, OSF‐1) is a secreted growth factor that shows mitogenic, chemotactic and transforming activity. While PTN expression is tightly regulated during embryogenesis and very limited in normal adult tissues, a marked PTN upregulation is seen in tumors including glioblastomas. Targeting of the PTN receptors, ALK and RPTP‐zeta, indicates a contribution of PTN‐activated signaling pathways in glioblastomas. However, the relevance of PTN expression itself is unknown especially since, besides PTN, at least one more growth factor, midkine (MK), signals through ALK and is expressed in glioblastoma. Here we demonstrate the biologic relevance of PTN in 2 glioblastoma cell linesin vitroandin vivo. We show that stable ribozyme‐targeting leads to a robust reduction of PTN mRNA and protein levels. This results in decreased cell proliferation, cell migration and soft agar colony formationin vitro. Comparing clonal ribozyme‐transfected cells with different residual PTN levels, we establish a PTN gene‐dose effect of glioblastoma cell proliferation. In a subcutaneous tumor xenograft mouse model,in vivogrowth is markedly reduced upon PTN depletion, which is paralleled by decreased PTN serum levels. Furthermore, the immunohistochemical analysis of the tumors shows reduced angiogenesis in PTN‐depleted tumors. We conclude that PTN is a rate‐limiting growth factor in glioblastoma. Since PTN is overexpressed in glioblastomas but rarely found in normal tissue, PTN may represent an attractive therapeutic target. © 2005 Wiley‐Liss, Inc.
Gender difference in estrogen receptor alpha promoter hypermethylation and its prognostic value in non‐small cell lung cancer
Authors: Lai Ji‐Ching , Cheng Ya‐Wen , Chiou Hui‐Ling , Wu Ming‐Fang , Chen Chin‐Yi , Lee Huei
Published: June 2005

It has been documented that estrogen receptor (ER) transcription silencing due to hypermethylation is linked to the tumor progression of breast, uterine and prostate cancers. Additionally, ER hypermethylation in lung tumors has been associated with the exposure of specific carcinogens in animal study. The role of hypermethylation‐induced ER transcription silencing in lung tumor progression and its prognostic value for non‐small cell lung cancer (NSCLC) patients remained unclear. In our study, ER hypermethylation of 123 lung tumors and adjacent normal parts were examined by methylation‐specific PCR (MSP). Estrogen receptor mRNA expression in lung tumors was determined by RT‐PCR. Our data indicated that ER hypermethylation was only detected in lung tumors, but not in adjacent normal lung tissues. This suggests that ER hypermethylation may be associated with lung tumorigenesis. Among the clinical parameters studied, only gender factor was correlated with ER hypermethylation with a higher frequency of ER hypermethylation being in male patients than in female patients (58 vs. 34%, p = 0.01). After being stratified by gender and cigarette smoking status, a similarly high prevalence of ER hypermethylation was found in male smoking and nonsmoking patients (60 vs. 61%) as compared to that of female nonsmoking patients (34%). To investigate if 17‐β estradiol (E2) was responsible for such gender difference in ER hypermethylation, a lung cancer A549 cell with ER hypermethylation and without ER mRNA expression was treated with E2 of various concentrations for defined time intervals to show that an E2 treatment could restore the expression of ER mRNA and eliminate ER hypermethylation. Western blot data also showed that acetylated histone 3 and histone 4 of chromatin were increased significantly by E2 treatment. Thus, E2 can make ER mRNA re‐expression by eliminating ER hypermethylation. To elucidate the prognostic value of ER hypermethylation, Kaplan‐Meier analysis was carried out to show that patients with ER hypermethylation had a poorer prognosis than those without ER hypermethylation. Such prognostic prediction, however, applied only to male (p = 0.0044) patients. Cox regression analysis further showed the feasibility of ER hypermethylation as an independent prognostic factor of NSCLC (p = 0.007). It is possible that antiestrogens may have different therapeutic values for male and female lung cancer patients. © 2005 Wiley‐Liss, Inc.
TP53BP2 locus is associated with gastric cancer susceptibility
Authors: Ju Hyoungseok , Lee Kyung‐A , Yang Misuk , Kim Hee‐Jin , Kang Changsoo Paul , Sohn Tae‐Sung , Rhee Jong‐Chul , Kang Changwon , Kim Jong‐Won
Published: June 2005

We investigated the association of the TP53BP2 locus with gastric cancer susceptibility in a Korean population. We assayed 9 single nucleotide polymorphisms (SNP) in an 82.5 kb region that included the TP53BP2 locus in 233 male gastric cancer patients and 390 unaffected healthy male controls. The allelic frequencies of 4 SNP within TP53BP2, g.206692C>T, g.198267A>T, g.164895G>A and g.152389A>T, differed significantly between cases and controls (p ≤ 0.0376). When compared to carriers of non‐risk alleles, individuals homozygotic for each of the risk alleles had a 50% increase in risk of gastric cancer (age‐adjusted odds ratio [OR] =≥ 1.48; p ≤ 0.0371). Furthermore, these 4 significantly associated SNP were in strong linkage disequilibrium (r2 ≥ 0.51). Haplotype analysis showed that individuals with the CAGA haplotype, consisting of the risk alleles at each SNP, had a 1.55‐fold higher risk for gastric cancer than individuals with the haplotype TTAT, consisting of the non‐risk alleles at each SNP (OR = 1.55; 95% confidence interval [CI] = 1.13–2.14; p = 0.00705). Two other SNP were not polymorphic in the study subjects, whereas the other 3 SNP, located toward the outside of the TP53BP2 locus, were not associated with gastric cancer susceptibility. Although the location of the pathogenic variant is not yet known, our results suggest that the TP53BP2 locus is associated with susceptibility to gastric cancer in the Korean population. © 2005 Wiley‐Liss, Inc.
Reduction of lipid peroxidation and H2O2‐mediated DNA damage by a red alga (Grateloupia filicina) methanolic extract
Authors: Athukorala Yasantha , Lee Ki‐Wan , Park Eun‐Ju , Heo Moon‐Soo , Yeo In‐Kyu , Lee Young‐Don , Jeon You‐Jin
Published: June 2005

The antioxidant activity of an extract of Grateloupia filicina was evaluated using linoleic acid and fish oil as substrates in an induct period at 65 °C. Furthermore, the algal extract was subjected to comet assay to evaluate its protecting ability for H2O2‐induced DNA damage in rat lymphocytes. Progression of oxidation was examined using weight gain, peroxide value (PV), 2‐thiobarbituric acid reactive substances and conjugated diene data. Effectiveness of the extract at 0.03 and 0.05% levels was superior to that of α‐tocopherol at 0.01% and the activity of 0.05% extract was higher than that of butylated hydroxyanisole and butylated hydroxytoluene at 0.01%. Also, the algal extract significantly inhibited H2O2 induced DNA damage in comet assay. The maximum DNA damage inhibition (68.9%) was recorded from the 50 µg ml−1 alga extract when the rat lymphocyte cells were treated with 50 µM H2O2. Copyright © 2005 Society of Chemical Industry
Disinfection of fishmeal with radiofrequency heating for improved quality and energy efficiency
Authors: Lagunas‐Solar Manuel C , Zeng Nolan X , Essert Timothy K , Truong Tin D , Piña Cecilia , Cullor James S , Smith Wayne L , Larraín Ricardo
Published: June 2005

Radiofrequency (RF) heating was investigated as an alternative to cooking, drying or chemical disinfection for the preservation of fishmeal and shown to be a highly effective process without any detectable effects, particularly on proteins, lipids or in vivo digestibility. The uniform and deep penetration of RF waves resulted in rapid and homogeneous heating allowing ∼4 times lower thermal loads to be used for >5 log10 (>99.999%) reduction in infection levels for Salmonella spp and for Escherichia coli O157:H7. Simultaneously, the natural flora was reduced by >3 log10 (>99.9%). The RF process can be operated in the 70–90 °C range and with high energy‐use efficiency (∼50%), which compares well with the 10–15% efficiency for conventional surface heating methods. Industry and expert laboratories confirmed these results. RF heating is thus a new alternative thermal process that is particularly appropriate for disinfecting fishmeal or for reprocessing it rapidly and efficiently with full retention of its natural attributes. Copyright © 2005 Society of Chemical Industry
Seed decontamination as an intervention step for eliminating Escherichia coli on salad vegetables and herbs
Authors: Warriner Keith , Ibrahim Faozia , Dickinson Matthew , Wright Charles , Waites William M
Published: June 2005

The efficacy of seed decontamination to enhance the safety of salad vegetables and herbs was evaluated. Seeds (celery, coriander, lettuce, spinach and watercress) were inoculated (at a level of 3–5 log cfu g−1) with either Escherichia coli P36 or Listeria monocytogenes NCTC 7973 and decontaminated with ozone gas, acidified sodium chlorite (ASC) or quaternary ammonium salt preparation (QAS). None of the treatments applied were initially effective at inactivating E coli on lettuce or spinach seeds as the bacterium could be recovered on the subsequent seedlings. However, as the cultivation period progressed, E coli numbers on plants derived from decontaminated seeds declined to below the level of detection. Interestingly, E coli persisted on the surface of lettuce and spinach leaves from inoculated non‐treated seeds throughout the 42‐day cultivation period. E coli also persisted on coriander derived from inoculated non‐treated seeds although it was isolated sporadically on plants derived from QAS‐decontaminated seed. E coli numbers progressively declined on celery and watercress regardless of the seed decontamination treatment being applied. No L monocytogenes was recovered from any of the seedlings, possibly because of the growth‐suppressing effect of endogenous microflora. The results suggest that effective on‐farm controls, such as seed decontamination, should be considered in order to reduce the risk of pathogens associated with salad vegetables and herbs. Copyright © 2005 Society of Chemical Industry
Fair trade, business and sustainable development
Authors: Young William , Utting Karla
Published: June 2005

Fair trade has never been more popular, with worldwide sales soaring. This editorial to the special issue of Sustainable Development on ‘Fair trade, business and sustainable development’ introduces the topic and papers within the special issue. It discusses the success of the ‘fairtrade’ brand and the impacts of fair trade schemes as well as the future of the brand. The paper concludes that this alternative trading system does work in practical terms and in helping marginalized producers in developing countries. Copyright © 2005 John Wiley & Sons, Ltd and ERP Environment.
α‐Glucosidase in Pompe's disease
Authors: Broadhead D. M. , Butterworth J.
Published: June 2005

Isoelectric precipitation at pH 5.0 and the use of the inhibitors, turanose, maltose and citrate, enabled the diagnosis of Pompe's disease to be made in dextran‐isolated leucocytes using 4‐methylumbelliferyl‐α‐D‐gluco‐pyranoside as substrate. These techniques were unnecessary with lymphocytes as the deficiency of acid α‐glucosidase could be shown directly.
Disordered intestinal function in glycogen storage disease
Authors: Milla P. J. , Atherton D. A. , Leonard J. V. , Wolff O. H. , Lake B. D.
Published: June 2005

The classical features of Type I glycogen storage disease (McKusick 23220) (GSD) are hepatomegaly, hypoglycaemia, and acidosis, enlargement of the kidneys and short stature. Glucose‐6‐phosphatase (EC 3.1.3.9) activity is defective not only in liver and kidney but also in small intestine (Fieldet al., 1965). In addition to the classical features, many patients suffer from episodes of diarrhoea (Fineet al., 1969).

At the Hospital for Sick Children, Great Ormond Street, patients with the commoner forms of hepatic glycogen storage disease have episodes of diarrhoea or loose stools more commonly than was suspected. We have investigated small intestinal function in three patients with Type I GSD by bothin vitro andin vivo techniques.
Fructose load test—anin vivo screening test designed to assess pyruvate dehydrogenase activity and interconversion
Authors: Stansbie D. , Sherriff R. J. , Denton R. M.
Published: June 2005

Anin vivo screening test is described, which is designed to assess the activity and interconversion of the human pyruvate dehydrogenase complex. Oral fructose was administered to six healthy subjects following (a) an overnight fast and (b) an oral glucose load. The rise in blood pyruvate and lactate levels following fructose was almost twice as great in the fasted state compared to the fed (post‐glucose) state. It is proposed that this difference is due to the conversion of pyruvate dehydrogenase to its active form, following feeding.
Prenatal and postnatal diagnostic difficulties in a family with rare alleles of the galactose‐1‐phosphate uridyl transferase locus
Authors: Christensen E. , Brandt N. J.
Published: June 2005

Whole‐blood galactose‐1‐phosphate uridyl transferase (Gal‐PUT) (EC 2.7.7.12) activity was absent in a newborn boy with galactosaemic symptoms. The symptoms disappeared on a galactose free diet.

In the next pregnancy prenatal diagnosis was performed. Gal‐PUT activity was measured by isotope technique and Gal‐PUT genotype was determined by gel electrophoresis. The mother was shown to be heterozygous Duarte/heterozygous Los Angeles, the father heterozygous Duarte/heterozygous galactosaemia. The fetus had the same genotype as the father. A normal girl without galactosaemic symptoms was born. Reinvestigation of the index case showed that he was also heterozygous Duarte/heterozygous galactosaemia.

It is concluded that the activity of Gal‐PUT should always be measured by isotope technique to prove the diagnosis of hereditary galactosaemia. Furthermore, Gal‐PUT‐genotyping in families with rare alleles is essential for safe prenatal diagnosis.
Perspectives on Surgery in the New South Africa
Authors: Bornman Philippus C. , Krige Jake E.J.
Published: June 2005

Radical changes have occurred in the health care system since the democratization of South Africa in 1994, with the emphasis on improving previously neglected community‐based primary health care. Because of the resultant financial constraints, funding of tertiary academic centers has been drastically cut which has compromised their proud record of service, teaching, and research excellence. Tertiary surgery has been particularly affected and now lags in the acquisition of new technologies which form an integral part of teaching and modern day practice. The acute shortage of full‐time surgeons in regional public hospitals has prompted the government to fill vacancies with surgeons from foreign countries. In stark contrast, an abundance of surgeons in the relatively small private sector enjoy the benefits of the very best of First World medicine. The ultimate goal is a seamless progression of effective health care at all levels. It behooves the main role players to ensure that the high standard of training of South African doctors, which has international recognition, is maintained during this transition period.
Are our ideas about Dst correct?
Authors: Grafe A.
Published: June 2005

Abstract. The idea of two separate storm time ring currents, a symmetric and an asymmetric one has accepted since the 1960s. The existence of a symmetric equatorial ring current was concluded from Dst. However, the asymmetric development of the low-latitude geomagnetic disturbance field during storms lead to the assumption of the real existence of an asymmetric ring current. I think it is time to inquire whether this conception is correct. Thus, I have investigated the development of the low-latitude geomagnetic field during all the magnetic local times under disturbed and quiet conditions. The storm on February 6–9, 1986 and a statistical analysis of many storms has shown that the asymmetry does not vanish during the storm recovery phase. The ratio between the recovery phase asymmetry and the main phase asymmetry is low only for powerful storms. Storms of moderate intensity show the opposite. The global picture of the field evolution of the February storm shows clear differences at different local times. For instance the main phase and recovery phase start time does not coincide with Dst. Also the ring current decay is not the same at different local times. Therefore, Dst gives an incorrect picture of the field development. Moreover, asymmetry does not disappear during international quiet days as the investigation of the low-latitude geomagnetic field shows. Considering all these observations, I think we must revise our ideas about the ring current. In my opinion only one ring current exists and this is an asymmetric one. This asymmetry increases during storms and develops rather fast to more or less symmetric conditions. However, in no case is it justified to conclude from Dst that a symmetric ring current exists.Key words. Magnetospheric physics (current systems; magnetospheric configuration and dynamics; storms and substorms)
Transport of thermal plasma above the auroral ionosphere in the presence of electrostatic ion-cyclotron turbulence
Authors: Zakharov V. E. , Meister C.-V.
Published: June 2005

Abstract. The electron component of intensive electric currents flowing along the geomagnetic field lines excites turbulence in the thermal magnetospheric plasma. The protons are then scattered by the excited electromagnetic waves, and as a result the plasma is stable. As the electron and ion temperatures of the background plasma are approximately equal each other, here electrostatic ion-cyclotron (EIC) turbulence is considered. In the nonisothermal plasma the ion-acoustic turbulence may occur additionally. The anomalous resistivity of the plasma causes large-scale differences of the electrostatic potential along the magnetic field lines. The presence of these differences provides heating and acceleration of the thermal and energetic auroral plasma. The investigation of the energy and momentum balance of the plasma and waves in the turbulent region is performed numerically, taking the magnetospheric convection and thermal conductivity of the plasma into account. As shown for the quasi-steady state, EIC turbulence may provide differences of the electric potential of ΔV≈1–10 kV at altitudes of 500 < h < 10 000 km above the Earth's surface. In the turbulent region, the temperatures of the electrons and protons increase only a few times in comparison with the background values.Key words. Magnetospheric physics (electric fields; plasma waves and instabilities)
A generation mechanism for chorus emission
Authors: Trakhtengerts V. Y.
Published: June 2005

Abstract. A chorus generation mechanism is discussed, which is based on interrelation of ELF/VLF noise-like and discrete emissions under the cyclotron wave-particle interactions. A natural ELF/VLF noise radiation is excited by the cyclotron instability mechanism in ducts with enhanced cold plasma density or at the plasmapause. This process is accompanied by a step-like deformation of the energetic electron distribution function in the velocity space, which is situated at the boundary between resonant and nonresonant particles. The step leads to the strong phase correlation of interacting particles and waves and to a new backward wave oscillator (BWO) regime of wave generation, when an absolute cyclotron instability arises at the central cross section of the geomagnetic trap, in the form of a succession of discrete signals with growing frequency inside each element. The dynamical spectrum of a separate element is formed similar to triggered ELF/VLF emission, when the strong wavelet starts from the equatorial plane. The comparison is given of the model developed using some satellite and ground-based data. In particular, the appearance of separate groups of chorus signals with a duration 2-10 s can be connected with the preliminary stage of the step formation. BWO regime gives a succession period smaller than the bounce period of energetic electrons between the magnetic mirrors and can explain the observed intervals between chorus elements.Key words. Magnetospheric physics (Energetic particles · trapped). Space plasma physics (wave-particle interactions; waves and instabilities)
Chemical ozone loss in the Arctic vortex in the winter 1995-96: HALOE measurements in conjunction with other observations
Authors: Müller R. , Grooß J. -U. , McKenna D. S. , Crutzen P. J. , Brühl C. , Russell J. M. , Gordley L. L. , Burrows J. P. , Tuck A. F.
Published: June 2005

Abstract. Severe chemical ozone loss has been detected in the Arctic in the winter and spring of 1995-96 by a variety of methods. Extreme reductions in column ozone due to halogen catalysed chemistry were derived from measurements of the Halogen Occultation Experiment (HALOE) on board the Upper Atmosphere Research Satellite in the Arctic vortex. Here, we discuss further aspects of the HALOE observations in the Arctic over this period. Potential problems, both in the data themselves and in the methodology of the data analysis are considered and the reason for the differences between the Arctic ozone losses deduced from HALOE data version 17 and 18 is analysed. Moreover, it is shown that HALOE measurements in the Arctic in winter and spring 1995-96 compare well with observations by other ground-based and satellite instruments.Key words. Chemical ozone loss (Arctic vortex 1995 · 96; halogen chemistry)
Inertia-gravity waves in the troposphere and lower stratosphere associated with a jet stream exit region
Authors: Thomas L. , Worthington R. M. , McDonald A. J.
Published: June 2005

Abstract. Radar measurements at Aberystwyth (52.4° N, 4.1° W) of winds at tropospheric and lower stratospheric heights are shown for 12-13 March 1994 in a region of highly curved flow, downstream of the jet maximum. The perturbations of horizontal velocity have comparable amplitudes in the troposphere and lower stratosphere with downward and upward phase propagation, respectively, in these two height regions. The sense of rotation with increasing height in hodographs of horizontal perturbation velocity derived for hourly intervals show downwards propagation of energy in the troposphere and upward propagation in the lower stratosphere with vertical wavelengths of 1.7 to 2.3 km. The results indicate inertia-gravity waves propagating in a direction similar to that of the jet stream but at smaller velocities. Some of the features observed contrast with those of previous observations of inertia-gravity waves propagating transverse to the jet stream. The interpretation of the hodographs to derive wave parameters has taken account of the vertical shear of the background wind transverse to the direction of wave propagation.Key words. Meteorology and atmospheric dynamics (mesoscale meteorology; middle atmosphere dynamics; waves and tides)