bluuebunny/crossref_metadata_2025 huggingface dataset:
The prevalence of undiagnosed pulmonary arterial hypertension in subjects with connective tissue disease at the secondary health care level of community‐based rheumatologists (the UNCOVER study)
Authors: Wigley Fredrick M. , Lima Joao A. C. , Mayes Maureen , McLain David , Chapin J. Lincoln , Ward‐Able Clive
Published: June 2005

Objective

Most of the data about the prevalence of pulmonary arterial hypertension (PAH) are from tertiary centers that are biased toward seeing more severe cases; therefore, the true prevalence of PAH among patients with connective tissue disease is unknown. We sought to determine the point prevalence of undiagnosed PAH in community‐based rheumatology practices.

Methods

The study design was a multicenter, prospective and retrospective survey and analysis of clinical cases in 50 community rheumatology practices. We evaluated a total of 909 patients with either scleroderma (systemic sclerosis [SSc]) or mixed connective tissue disease (MCTD). If a subject had not been diagnosed as having PAH, then a new Doppler echocardiogram was obtained to measure cardiac parameters, including estimated right ventricular systolic pressure (ERVSP), and a full review of medical records was done.

Results

Of 909 screened patients, 791 were evaluable and completed the study; 669 had not previously been studied for PAH. Of these 669 patients, 89 (13.3%) were found by Doppler echocardiography to have an ERVSP of ≥40 mm Hg. Of these 89 patients, 82 (92.1%) had SSc and 7 (7.9%) had MCTD. The total prevalence of PAH in the survey was 26.7% (211 of 791 patients, including 122 with known PAH and 89 newly diagnosed as having PAH). Doppler echocardiographic data showed 20 of 89 patients (22.5%) with ERVSP of ≥50 mm Hg, 20 of 89 patients (22.5%) with increased RV dimension, and 25 of 89 patients (28.1%) with right atrial enlargement. Patients with ERVSP ≥40 mm Hg had decreased exercise tolerance compared with those with ERVSP <40 mm Hg (27% compared with 9.5%, respectively, were severely symptomatic).

Conclusion

A significant number of patients with SSc or MCTD (13.3%) followed up in a community rheumatology practice setting have undiagnosed elevated ERVSP consistent with PAH.
Risk and case characteristics of tuberculosis in rheumatoid arthritis associated with tumor necrosis factor antagonists in Sweden
Authors: Askling Johan , Fored C. Michael , Brandt Lena , Baecklund Eva , Bertilsson Lennart , Cöster Lars , Geborek Pierre , Jacobsson Lennart T. , Lindblad Staffan , Lysholm Jörgen , Rantapää‐Dahlqvist Solbritt , Saxne Tore , Romanus Victoria , Klareskog Lars , Feltelius Nils
Published: June 2005

Objective

Because treatment with tumor necrosis factor (TNF) antagonists may increase the risk of tuberculosis (TB), and because knowledge of the risk of TB in rheumatoid arthritis (RA) not treated with biologics is scarce and of uncertain generalizability to low‐risk populations, this study sought to determine the risk of TB among Swedish patients with RA.

Methods

Using data from Swedish nationwide and population‐based registers and data from an ongoing monitoring program of TNF antagonists, the relative risks of TB in patients with RA (versus the general population) and of TB associated with TNF antagonists (versus RA patients not treated with biologics) were determined by comparing the incidence of hospitalization for TB in 3 RA cohorts and 2 general population cohorts from 1999 to 2001. We also reviewed the characteristics of all reported cases of TB in RA patients treated with TNF antagonists in Sweden and calculated the incidence of TB per type of TNF antagonist between 1999 and 2004.

Results

During 1999–2001, RA patients who were not treated with TNF antagonists were at increased risk of TB versus the general population (relative risk 2.0, 95% confidence interval [95% CI] 1.2–3.4). RA patients treated with TNF antagonists had a 4‐fold increased risk of TB (relative risk 4.0, 95% CI 1.3–12) versus RA patients not treated with TNF antagonists. The reported TB cases during 1999–2004 in RA patients exposed to TNF antagonists (9 infliximab, 4 etanercept, 2 both) were predominantly pulmonary. TB occurred up to 3 years following the start of treatment.

Conclusion

Irrespective of whether TNF antagonists are administered, Swedish patients with RA are at increased risk of TB. During 1999–2001, TNF antagonists were associated with an increased risk of TB, up to 4‐fold in magnitude. This increased risk may persist over time during treatment and is related to both infliximab and etanercept.
Association of cartilage defects with loss of knee cartilage in healthy, middle‐age adults: A prospective study
Authors: Cicuttini Flavia , Ding Changhai , Wluka Anita , Davis Susan , Ebeling Peter R. , Jones Graeme
Published: June 2005

Objective

The significance of asymptomatic knee cartilage defects in healthy individuals is not known. The aim of this study was to examine the association between cartilage defects in the knee and cartilage volume both cross‐sectionally and longitudinally in healthy, middle‐age adults.

Methods

Eighty‐six healthy men and women (mean ± SD age 53.8 ± 8.8 years) underwent T1‐weighted fat‐suppressed magnetic resonance imaging of their dominant knees at baseline and at the 2‐year followup visit. Knee cartilage volume was measured. Cartilage defects were scored according to a grading system (0–4) and as present (a defect score of ≥2) or absent in the medial and lateral tibiofemoral compartments.

Results

Cartilage defects in the medial and lateral tibiofemoral compartments were very common (in 61% and 43% of subjects, respectively). Those with cartilage defects had a 25% reduction in medial tibial cartilage volume, a 15% reduction in lateral tibial cartilage volume, and a 19% reduction in total femoral cartilage volume relative to those with no cartilage defects in cross‐sectional analyses (all P < 0.05). In the medial tibiofemoral compartment, the annual loss of tibial cartilage in those with cartilage defects was 2.5% (95% confidence interval [95% CI] 2.2%, 3.1%) compared with an annual loss of tibial cartilage of 1.3% (95% CI 0.5%, 2.0%) in those with no defects (P = 0.028), independent of other known risk factors for osteoarthritis (OA).

Conclusion

These data suggest that the presence of asymptomatic, non–full‐thickness medial tibiofemoral cartilage defects identifies healthy individuals most likely to lose knee cartilage in the absence of radiographic knee OA. Thus, interventions aimed at reducing or reversing cartilage defects may reduce the risk of subsequent knee OA.
Retroviral gene transfer of an antisense construct against membrane type 1 matrix metalloproteinase reduces the invasiveness of rheumatoid arthritis synovial fibroblasts
Authors: Rutkauskaite Edita , Volkmer Dagmar , Shigeyama Yukio , Schedel Jörg , Pap Geza , Müller‐Ladner Ulf , Meinecke Ingmar , Alexander Dorothea , Gay Renate E. , Drynda Susanne , Neumann Wolfram , Michel Beat A. , Aicher Wilhelm K. , Gay Steffen , Pap Thomas
Published: June 2005

Objective

Membrane type 1 matrix metalloproteinase (MT1‐MMP) is expressed prominently in rheumatoid arthritis synovial fibroblasts (RASFs), but the specific contribution of MT1‐MMP to fibroblast‐mediated destruction of articular cartilage is incompletely understood. This study used gene transfer of an antisense expression construct to assess the effects of MT1‐MMP inhibition on the invasiveness of RASFs.

Methods

Retroviral gene transfer of a pLXIN vector–based antisense RNA expression construct (MT1‐MMPαS) to MT1‐MMP was used to stably transduce RASFs. Levels of MT1‐MMP RNA and protein were determined by quantitative polymerase chain reaction, Western blotting, and immunocytochemistry in MT1‐MMPαS–transduced RASFs as well as in control cells, with monitoring for 60 days. The effects of MT1‐MMPαS on the invasiveness of RASFs were analyzed in the SCID mouse coimplantation model of RA.

Results

MT1‐MMPαS–transduced RASFs produced high levels of antisense RNA that exceeded endogenous levels of MT1‐MMP messenger RNA by 15‐fold and resulted in a down‐regulation of MT1‐MMP at the protein level. Inhibition of MT1‐MMP production was maintained for 60 days and significantly reduced the invasiveness of RASFs in the SCID mouse model. Whereas prominent invasion into cartilage by nontransduced and mock‐transduced RASFs was observed (mean invasion scores 3.0 and 3.1, respectively), MT1‐MMPαS–transduced cells showed only moderate invasiveness (mean invasion score 1.8; P < 0.05).

Conclusion

The data demonstrate that an antisense RNA expression construct against MT1‐MMP can be generated and expressed in RASFs for at least 60 days. Inhibition of MT1‐MMP significantly reduces the cartilage degradation by RASFs.
Infliximab, but not etanercept, induces IgM anti–double‐stranded DNA autoantibodies as main antinuclear reactivity: Biologic and clinical implications in autoimmune arthritis
Authors: de Rycke Leen , Baeten Dominique , Kruithof Elli , Van den Bosch Filip , Veys Eric M. , de Keyser Filip
Published: June 2005

Objective

To analyze the clinical and biologic correlates of autoantibody induction during longer‐term tumor necrosis factor α (TNFα) blockade with either the monoclonal antibody infliximab or the soluble receptor etanercept.

Methods

Thirty‐four patients with spondylarthropathy (SpA) and 59 patients with rheumatoid arthritis (RA) were treated with infliximab for 2 years. Additionally, 20 patients with SpA were treated with etanercept for 1 year. Sera were blindly analyzed for antinuclear antibodies (ANAs), anti–double‐stranded DNA (anti‐dsDNA) antibodies, anti–extractable nuclear antigen (anti‐ENA) antibodies, and antihistone, antinucleosome, and anticardiolipin antibodies (aCL). The anti‐dsDNA antibodies were isotyped.

Results

High numbers of infliximab‐treated patients with SpA or RA had newly induced ANAs (61.8% and 40.7%, respectively) and anti‐dsDNA antibodies (70.6% and 49.2%, respectively) after 1 year, but no further increase between year 1 and year 2 was observed. In contrast, induction of ANAs and anti‐dsDNA antibodies was observed only occasionally in the etanercept‐treated patients with SpA (10% of patients each). Isotyping revealed almost exclusively IgM or IgM/IgA anti‐dsDNA antibodies, which disappeared upon interruption of treatment. Neither infliximab nor etanercept induced other lupus‐related reactivities such as anti‐ENA antibodies, antihistone antibodies, or antinucleosome antibodies, and no clinically relevant lupus‐like symptoms were observed. Similarly, infliximab but not etanercept selectively increased IgM but not IgG aCL titers.

Conclusion

The prominent ANA and anti‐dsDNA autoantibody response is not a pure class effect of TNFα blockers, is largely restricted to short‐term IgM responses, and is not associated with other serologic or clinical signs of lupus. Similar findings with aCL suggest that modulation of humoral immunity may be a more general feature of infliximab treatment.
Distribution of synaptic zinc in the macaque monkey amygdala
Authors: Ichinohe Noritaka , Rockland Kathleen S.
Published: June 2005

We have mapped the macaque amygdala for the distribution of synaptic zinc (Zn), a co‐factor of glutamate implicated in plasticity, as well as in several excitotoxic and other pathophysiological conditions. In brief, we found that the amygdala is Zn enriched in all nuclear groups (i.e., basolateral and cortical groups, as well as central and medial nuclei) but with marked differences in density. By comparing parallel tissue series histologically reacted for Zn and parvalbumin (PV), we further found that regions high in Zn are typically low in PV neuropil. In the basolateral group, there is a particularly distinct dorsoventral gradation such that Zn levels are most dense ventrally, i.e., in the paralaminar nucleus, the ventral division of the lateral nucleus, and the parvicellular divisions of both the basal nucleus and the accessory basal nucleus. PV levels are least dense in these same regions. For the central and medial nuclei, there is a slight mediolateral gradient, with Zn levels being higher medially. PV is low overall in these nuclei. Electron microscopic results confirmed that Zn is contained in synaptic boutons. These form asymmetrical, presumably excitatory, synapses, and the postsynaptic targets are mainly spines of projection neurons. The inhomogeneous distribution of Zn in the monkey amygdala may be related to different types or degrees of plasticity among the amygdaloid subnuclei. The complementary distribution with PV parallels that of several other substances and is interesting in the context of subnuclear vulnerability for human neuronal disease, such as seizure and Alzheimer's disease. J. Comp. Neurol. 489:135–147, 2005. © 2005 Wiley‐Liss, Inc.
Origin, fate, and function of the components of the avian germ disc region and early blastoderm: Role of ooplasmic determinants
Authors: Callebaut Marc
Published: June 2005

In the avian oocytal germ disc region, at the end of oogenesis, we discerned four ooplasms (α, β, γ, δ) presenting an onion‐peel distribution (from peripheral and superficial to central and deep. Their fate was followed during early embryonic development. The most superficial and peripheral α ooplasm plays a fundamental role during cleavage. The β ooplasm, originally localized in the peripheral region of the blastodisc, becomes mainly concentrated in the primitive streak. At the moment of bilateral symmetrization, a spatially oblique, sickle‐shaped uptake of γ and δ ooplasms occurs so that γ and δ ooplasms become incorporated into the deeper part of the avian blastoderm. These ooplasms seem to contain ooplasmic determinants that initiate either early neurulation or gastrulation events. The early neural plate‐inducing structure that forms a deep part of the blastoderm is the δ ooplasm‐containing endophyll (primary hypoblast). Together with the primordial germ cells, it is derived from the superficial centrocaudal part of the nucleus of Pander, which also contains δ ooplasm. The other structure (γ ooplasm) that is incorporated into the caudolateral deep part of the blastoderm forms Rauber's sickle. It induces gastrulation in the concavity of Rauber's sickle and blood island formation exterior to Rauber's sickle. Rauber's sickle develops by ingrowth of blastodermal cells into the γ ooplasm, which surrounds the nucleus of Pander. Rauber's sickle constitutes the primary major organizer of the avian blastoderm and generates only extraembryonic tissues (junctional and sickle endoblast). By imparting positional information, it organizes and dominates the whole blastoderm (controlling gastrulation, neurulation, and coelom and cardiovascular system formation). Fragments of the horns of Rauber's sickle extend far cranially into the lateral quadrants of the unincubated blastoderm, so that often Rauber's sickle material forms three quarters of a circle. This finding explains the regulative capacities of isolated blastoderm parts, with the exception of the anti‐sickle region and central blastoderm region, where no Rauber's sickle material is present. In avian blastoderms, there exists a competitive inhibition by Rauber's sickle on the primitive streak and neural plate‐inducing effects of sickle endoblast. Avian primordial germ cells contain δ ooplasm derived from the superficial part of the nucleus of Pander. Their original deep and central ooplasmic localization has been confirmed by the use of a chicken vasa homologue. We conclude that the unincubated blastoderm consists of three elementary tissues: upper layer mainly containing β ooplasm, endophyll containing δ ooplasm, and Rauber's sickle containing γ ooplasm). These elementary tissues form before the three classic germ layers have developed. Developmental Dynamics 233:1194–1216, 2005. © 2005 Wiley‐Liss, Inc.
Hybrid 2D and 3D Frameworks Based on ϵ‐Keggin Polyoxometallates: Experiment and Simulation
Authors: Dolbecq Anne , Mellot‐Draznieks Caroline , Mialane Pierre , Marrot Jérôme , Férey Gérard , Sécheresse Francis
Published: June 2005

The ϵ‐Keggin polyoxomolybdate {ϵ‐PMoV8MoVI4O40–x(OH)xM4} is a versatile building unit, with M being either a ZnII or a LaIII capping ion located at the vertices of a slightly distorted tetrahedron. The charge of the Keggin unit depends on the number of protonated oxo bridging ligands, which has been shown to vary from 0 to 5. The Keggin entity can thus be either an anion (M = Zn, x = 0) or a cation (M = La, x = 3–5). The Zn derivative has been generated in situ by hydrothermal synthesis and forms a 2D material built from the connection of the cations by 4,4'‐bipyridine ligands linked to the capping ZnII ions. The reaction of the chloride salt of the La derivative with di‐, tri‐ and tetrasubstituted benzenecarboxylate ligands has allowed us to isolate 2D and 3D materials. The 3D materials seem to be the first examples of hybrid open frameworks based on Keggin building blocks. The 3D framework built from the connection of ϵ‐Keggin units by trimesate ions exhibits tunnels filled only by water molecules, which can be partly removed and reintroduced at room temperature. Besides these experimental results, simulation has allowed us to generate two virtual hybrid structures derived from those of known silicates by replacing the Si ions by hypothetical ϵ‐Keggin cations and the O‐bridging ligands by terephthalate ions, thus showing that 3D frameworks with large pores can be envisioned in the chemistry of hybrid organic–inorganic materials based on ϵ‐Keggin units and motivating further experimental investigations. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Extending the NHC Concept: C–C Coupling Catalysis by a PdII Carbene (rNHC) Complex with Remote Heteroatoms
Authors: Schneider Sabine K. , Roembke Patric , Julius Gerrit R. , Loschen Christoph , Raubenheimer Helgard G. , Frenking Gernot , Herrmann Wolfgang A.
Published: June 2005

A palladium complex, trans‐Cl(PPh3)2Pd{Ca‐cyclo‐C6H4‐o‐N(Me)C=CbH}(Ca—Cb), that contains a carbene ligand with remote heteroatoms (rNHC) is much more active in certain C–C coupling reactions than comparably simple NHC‐ and phosphane‐containing precatalysts. The rNHC ligand binds strongly by electrostatic as well as orbital interaction to the metal. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Electrochemical and Spectroscopic Study of the Interaction of Indirubin with DNA
Authors: Ye Bao‐Xian , Yuan Li‐Jie , Chen Chun , Tao Jing‐Chao
Published: June 2005

The interaction of indirubin with DNA was studied by differential pulse voltammetry (DPV) and linear sweep voltammetry (LSV) at the bare or DNA‐modified electrode and UV‐vis or IR spectra. As a result of intercalating of this drug into the double helical structure of DNA, the DPV of indirubin shows that peak potentials shift and peak currents decrease with the addition of DNA. UV‐vis spectra exhibits that the absorption intensity of indirubin at 538.7 nm−1 decreases, which indicates that the anticancer herbal drug indirubin binds DNA. In addition, IR‐spectra of DNA and DNA‐indirubin adduct imply indirubin interacts with the phosphate groups of DNA by hydrogen bond or electrostatic interaction. Under our experiment conditions, the decrease of peak current is proportional to DNA concentration, which can be applied to estimate DNA concentration. The results indicate that the herbal drug indirubin can interfere with the DNA by intercalating into the double helix of DNA and interacting with the phosphate groups of DNA.
Combination of forecasts using self‐organizing algorithms
Authors: He Changzheng , Xu Xiaozhan
Published: June 2005

Based on the theories and methods of self‐organizing data mining, a new forecasting method, called self‐organizing combining forecasting method, is proposed. Compared with optimal linear combining forecasting methods and neural networks combining forecasting methods, the new method can improve the forecasting capability of the model. The superiority of the new method is justified and demonstrated by real applications. Copyright © 2005 John Wiley & Sons, Ltd.
Quantitative evaluation of automated skull‐stripping methods applied to contemporary and legacy images: Effects of diagnosis, bias correction, and slice location
Authors: Fennema‐Notestine Christine , Ozyurt I. Burak , Clark Camellia P. , Morris Shaunna , Bischoff‐Grethe Amanda , Bondi Mark W. , Jernigan Terry L. , Fischl Bruce , Segonne Florent , Shattuck David W. , Leahy Richard M. , Rex David E. , Toga Arthur W. , Zou Kelly H. , Brown Gregory G.
Published: June 2005

Performance of automated methods to isolate brain from nonbrain tissues in magnetic resonance (MR) structural images may be influenced by MR signal inhomogeneities, type of MR image set, regional anatomy, and age and diagnosis of subjects studied. The present study compared the performance of four methods: Brain Extraction Tool (BET; Smith [2002]: Hum Brain Mapp 17:143–155); 3dIntracranial (Ward [1999] Milwaukee: Biophysics Research Institute, Medical College of Wisconsin; in AFNI); a Hybrid Watershed algorithm (HWA, Segonne et al. [2004] Neuroimage 22:1060–1075; in FreeSurfer); and Brain Surface Extractor (BSE, Sandor and Leahy [1997] IEEE Trans Med Imag 16:41–54; Shattuck et al. [2001] Neuroimage 13:856–876) to manually stripped images. The methods were applied to uncorrected and bias‐corrected datasets; Legacy and Contemporary T1‐weighted image sets; and four diagnostic groups (depressed, Alzheimer's, young and elderly control). To provide a criterion for outcome assessment, two experts manually stripped six sagittal sections for each dataset in locations where brain and nonbrain tissue are difficult to distinguish. Methods were compared on Jaccard similarity coefficients, Hausdorff distances, and an Expectation‐Maximization algorithm. Methods tended to perform better on contemporary datasets; bias correction did not significantly improve method performance. Mesial sections were most difficult for all methods. Although AD image sets were most difficult to strip, HWA and BSE were more robust across diagnostic groups compared with 3dIntracranial and BET. With respect to specificity, BSE tended to perform best across all groups, whereas HWA was more sensitive than other methods. The results of this study may direct users towards a method appropriate to their T1‐weighted datasets and improve the efficiency of processing for large, multisite neuroimaging studies. Hum. Brain Mapping, 2005. © 2005 Wiley‐Liss, Inc.
Biallelic somatic inactivation of the NF1 gene through chromosomal translocations in a sporadic neurofibroma
Authors: Storlazzi Clelia Tiziana , Von Steyern Fredrik Vult , Domanski Henryk A. , Mandahl Nils , Mertens Fredrik
Published: June 2005

Neurofibroma is a benign tumor originating from Schwann cells in peripheral nerve sheaths and may occur as a sporadic tumor or as part of the dominantly inherited tumor syndrome NF1. NF1 is caused by constitutional mutations in the NF1 gene, located in chromosome band 17q11. Whereas the involvement of the NF1 gene in neurofibroma development in NF1 patients has been fairly well characterized, the significance of inactivation of this gene in sporadic neurofibromas remains less well investigated. Inactivation of both copies of NF1 has been described in a few neurofibromas from NF1 patients, and LOH at the same locus has been reported in additional cases. In the present study, we report the cytogenetic and molecular cytogenetic findings in a sporadic neurofibroma that at G‐banding analysis showed a translocation between one chromosome 2 and the long arms of both copies of chromosome 17. FISH analysis using a set of 3 BAC clones covering the entire coding region of NF1 revealed the complete loss of one allele and the deletion of the 5′ portion of the second allele as a result of 2 translocation events. To the best of our knowledge, this represents the first demonstration of a somatic biallelic inactivation of the NF1 gene in neurofibroma, providing further evidence for the importance of NF1 inactivation also in sporadic neurofibromas. © 2005 Wiley‐Liss, Inc.
Antiinvasive effect of xanthohumol, a prenylated chalcone present in hops (Humulus lupulus L.) and beer
Authors: Vanhoecke Barbara , Derycke Lara , Van Marck Veerle , Depypere Herman , De Keukeleire Denis , Bracke Marc
Published: June 2005

The female inflorescences of the hop plant (Humulus lupulus L.) are essential during brewing to add taste and flavor to beer and to stabilize beer foam. Xanthohumol, the main prenylated chalcone in hops, was investigated for its antiinvasive activity on human breast cancer cell lines (MCF‐7 and T47‐D) in vitro. Xanthohumol was able to inhibit the invasion of MCF‐7/6 cells at 5 μM in the chick heart invasion assay and of T47‐D cells in the collagen invasion assay. Xanthohumol inhibited growth of MCF‐7/6 and T47‐D cells, but not of chick heart cells. Moreover, it induced apoptosis of these tumor cells as demonstrated by the cleavage of nuclear PARP after 48 hr treatment. To probe the mechanism of the antiinvasive effect of xanthohumol, involvement of the E‐cadherin/catenin invasion‐suppressor complex was investigated. An aggregation assay demonstrated stimulation of aggregation of MCF‐7/6 cells in the presence of 5 μM xanthohumol and this could be completely inhibited by an antibody against E‐cadherin. Xanthohumol upregulates the function of the E‐cadherin/catenin complex and inhibits invasion in vitro, indicating a possible role as an antiinvasive agent in vivo as well. © 2005 Wiley‐Liss, Inc.
Expression of RPIP9 (Rap2 interacting protein 9) is activated in breast carcinoma and correlates with a poor prognosis
Authors: Raguz Selina , De Bella Manuela Tamburo , Slade Martin J. , Higgins Christopher F. , Coombes R. Charles , Yagüe Ernesto
Published: June 2005

MDR1 is upregulated in many tumors. We have previously detected activation of the MDR1 upstream promoter in metastatic breast cancer cells. MDR1 overlaps with an uncharacterized gene transcribed from the opposite strand, coding for Rap2 interacting protein 9 (RPIP9). Rap2 belongs to the Ras superfamily of GTPases, whose role in breast cancer remains unknown. We developed sensitive methods for detecting and quantifying RPIP9 mRNA and used it to identify these transcripts in normal human tissues, 60 biopsies of primary breast carcinoma, in isolated epithelial cells both from the primary tumor and from associated lymph nodes, and from bone marrow biopsies of 74 breast cancer patients. RPIP9 is expressed at high levels in normal testis, brain and adrenal gland, and at very low levels in normal breast. Tumorigenic breast carcinoma cell lines expressed RPIP9, whereas MCF‐10A and HBL‐100 that do not form tumors in nude mice had undetectable levels of RPIP9 mRNA. RPIP9 was activated in a high proportion of breast carcinomas (61.6%; n = 60) and a significant correlation with metastatic lymph node invasion (N = 0–3 vs. N > 3, where N = number of lymph nodes invaded; p = 0.031) was found. RPIP9 mRNA could be detected in malignant epithelial cells isolated from the primary tumor and from metastasized lymph nodes as well as in the bone marrow of significantly more poor‐prognosis (N > 3) than better‐prognosis (N = 0–3) patients (p = 0.001). Therefore, activation of RPIP9 occurs during the malignant breast epithelial transformation and increases with progression toward an invasive phenotype. © 2005 Wiley‐Liss, Inc.
Antibodies to JC and BK viruses among persons with non‐Hodgkin lymphoma
Authors: Engels Eric A. , Rollison Dana E. , Hartge Patricia , Baris Dalsu , Cerhan James R. , Severson Richard K. , Cozen Wendy , Davis Scott , Biggar Robert J. , Goedert James J. , Viscidi Raphael P.
Published: June 2005

Two related polyomaviruses, JC virus (JCV) and BK virus (BKV), commonly cause lifelong infections in humans, with periodic reactivation manifesting as viral shedding in urine. Because JCV can infect lymphocytes and cause chromosomal damage, it is a plausible candidate to cause non‐Hodgkin lymphoma (NHL). To test this hypothesis, we measured IgG antibodies to JCV and BKV capsids using a virus‐like particle enzyme immunoassay in 3 separate groups of subjects. First, in a U.S. population‐based case‐control study of NHL (724 cases, 622 controls), we found lower JCV antibody levels in cases than controls (median optical density = 0.12 vs. 0.21, p < 0.0001); likewise, JCV seroprevalence was lower in cases (49% vs. 59%, adjusted odds ratio [OR] = 0.70, 95% confidence interval [CI] = 0.56–0.87). In contrast, BKV antibody levels did not differ between groups. Second, we found that JCV and BKV antibody levels changed little over time among 24 NHL patients receiving chemotherapy. Third, we evaluated 126 homosexual men, of whom 46 were shedding JCV and 14 were shedding BKV in urine. Antibody levels were much higher in shedders than non‐shedders (JCV: median optical density = 0.67 vs. 0.07, p < 0.0001; BKV: 0.87 vs. 0.40, p = 0.003), indicating that these antibodies are a marker for viral replication. Because no deficit of BKV antibody was seen in NHL cases, and because antibody levels did not change materially with chemotherapy, we suggest that the lower levels of JCV antibody observed in NHL patients may not be due entirely to a disease or treatment effect. Additional research is needed to determine whether JCV replication is decreased in individuals with NHL and whether these findings are consistent with an etiologic role for JCV in NHL. © 2005 Wiley‐Liss, Inc.
Structural variation in the inner ears of four deep‐sea elopomorph fishes
Authors: Buran Bradley N. , Deng Xiaohong , Popper Arthur N.
Published: June 2005

Deep‐sea fishes have evolved in dark or dimly lit environments devoid of the visual cues available to shallow‐water species. Because of the limited opportunity for visual scene analysis by deep‐sea fishes, it is reasonable to hypothesize that the inner ears of at least some such species may have evolved structural adaptations to enhance hearing capabilities in lieu of vision. As an initial test of this hypothesis, scanning electron microscopy was used to examine the structure of the inner ears of four deep‐sea elopomorph species inhabiting different depths: Synaphobranchus kaupii, Synaphobranchus bathybius, Polyacanthonotus challengeri, and Halosauropsis macrochir. The shape of the sensory epithelia and hair cell ciliary bundle orientation of the saccule, lagena, and utricle, the three otolithic organs associated with audition and vestibular function, are described. The saccules of all four species have a common, alternating ciliary bundle orientation pattern. In contrast, the lagena exhibits more interspecific diversity in shape and ciliary bundle orientation, suggesting that it has special adaptations in these species. The macula neglecta, a sensory epithelium of unknown function, is present in all four species. J. Morphol. © 2005 Wiley‐Liss, Inc.
Comparison of calcium lactate with chlorine as a washing treatment for fresh‐cut lettuce and carrots: quality and nutritional parameters
Authors: Martín‐Diana Ana Belén , Rico Daniel , Barry‐Ryan Catherine , Frías Jesús M , Mulcahy Jemina , Henehan Gary TM
Published: June 2005

The efficacies of calcium lactate and chlorine washing treatments of fresh‐cut lettuce and carrots were compared during storage at 4 °C over 10 days. The gas composition of packages, colour, enzyme activity, texture, sensory attributes, microflora and levels of ascorbic acid and carotenoids were evaluated at 1, 3, 7 and 10 days. Calcium lactate treatment was not significantly different to chlorine treatment (p < 0.05) in terms of maintaining colour, texture and acceptability of fresh‐cut lettuce and carrots during the entire storage period. The washing treatments did not affect levels of ascorbic acid of fresh‐cut lettuce or carrots. Carotenoid levels were higher in calcium lactate‐treated carrots than chlorine‐treated samples at the end of storage. Mesophilic, psychrotrophic and lactic acid bacteria counts were not significantly different between treatments for both vegetables. Copyright © 2005 Society of Chemical Industry
Aspergillus flavus population isolated from soil of Argentina's peanut‐growing region. Sclerotia production and toxigenic profile
Authors: Barros Germán , Torres Adriana , Chulze Sofía
Published: June 2005

The Aspergillus flavus population was evaluated in the period 1998–2001 in soil samples from the peanut‐growing region in Argentina. A total of 369 A flavus isolates were examined for sclerotia, aflatoxin and cyclopiazonic acid production. The L phenotype was isolated in a higher percentage than the S phenotype and represented 59% of the total isolates. Statistical analysis showed significant differences between L, S and non‐sclerotial strains with regard to aflatoxin and cyclopiazonic acid production (p < 0.05). The S strains produced higher mycotoxin levels than the L and non‐sclerotial strains. About 10% of the S strains had an unusual pattern of mycotoxin production because they simultaneously produce aflatoxins B and G and CPA. The SBG strains isolated in the present study have all morphological and microscopic characteristics of A flavus. These strains are of concern in food safety, as there is a higher probability of aflatoxin contamination in peanuts. Copyright © 2005 Society of Chemical Industry
Kufor Rakeb Disease: Autosomal recessive, levodopa‐responsive parkinsonism with pyramidal degeneration, supranuclear gaze palsy, and dementia
Authors: Williams David R. , Hadeed Ali , al‐Din Amir S. Najim , Wreikat Abdel‐Latif , Lees Andrew J.
Published: June 2005

Kufor Rakeb disease is an autosomal recessive disorder characterized by subacute, juvenile‐onset, levodopa‐responsive parkinsonism, pyramidal signs, dementia, and a supranuclear gaze palsy. It was originally described more than a decade ago, and linkage analysis identified a locus on chromosome 1p36 that was previously assigned PARK9. We have further characterized the clinical picture and specifically re‐assessed the response to levodopa in the original family, in the northern highlands of Jordan. In the 4 surviving patients, there has been a narrowing of the therapeutic window for levodopa with the emergence of peak‐dose dyskinesias with increased spasticity and cognitive decline. Several new features were identified, including facial‐faucial‐finger mini‐myoclonus, visual hallucinations, and oculogyric dystonic spasms. © 2005 Movement Disorder Society
A pilot tolerability and efficacy trial of sodium oxybate in ethanol‐responsive movement disorders
Authors: Frucht Steven J. , Bordelon Yvette , Houghton William H. , Reardan Dayton
Published: June 2005

Sodium oxybate is currently approved in the United States exclusively for the treatment of cataplexy in narcoleptic patients. In a prior article published in this journal, we reported a patient with severe posthypoxic myoclonus whose myoclonus improved with ethanol and also with treatment with sodium oxybate. We extend this preliminary observation to five other patients with ethanol‐responsive movement disorders in an open‐label, dose‐titration, add‐on, 8‐week trial. All five patients (one with severe alcohol‐responsive posthypoxic myoclonus, two with ϵ‐sarcoglycan–linked myoclonus–dystonia, and two with essential tremor) experienced improvement from baseline of 50% or greater as measured by blinded videotape review. Tolerability was satisfactory, with dose‐dependent sedation as the most common side effect. Further studies of this drug in hyperkinetic movement disorders are warranted. © 2005 Movement Disorder Society
Biofumigation: environmental impacts on the biological activity of diverse pure and plant‐derived isothiocyanates
Authors: Matthiessen John N , Shackleton Mark A
Published: June 2005

Four pure isothiocyanates (methyl, 2‐propenyl, benzyl and 2‐phenylethyl isothiocyanate), hydrolysing tissue of two brassicas rich in either 2‐propenyl or 2‐phenylethyl isothiocyanate, and the methyl isothiocyanate‐generating pesticide metam‐sodium were tested in vapour exposure tests for biological activity against a model soil insect both in vitro and in the presence of three contrasting soils and under four temperatures from 5 to 20 °C. The purpose was to develop an understanding of the factors controlling isothiocyanate release and maintenance in soil in order to identify advantageous attributes to seek in utilising brassicas for isothiocyanate‐based biofumigation. Methyl isothiocyanate, structurally the simplest and the most volatile, was the most biologically active isothiocyanate under all conditions. It was less affected by the presence of soil and by lower temperature than the longer‐chain aliphatic 2‐propenyl isothiocyanate. The activity of the less volatile aromatic isothiocyanates was reduced much more by soil, with a decline up to many thousand‐fold in the presence of soil with high organic matter content at lower temperature. Metam‐sodium closely reflected the methyl isothiocyanate results. The results indicate that brassicas rich in aliphatic isothiocyanates are more likely to have the potential to exert stronger isothiocyanate‐based biofumigation effects than those similarly rich in aromatic isothiocyanates. Copyright © 2005 Society of Chemical Industry
Trends in water usage and knowledge of arsenicosis in Bangladesh: findings from successive national surveys
Authors: Caldwell Bruce K. , Smith Wayne T. , Caldwell J. C. , Mitra S. N.
Published: June 2005

The presence of arsenic in tubewell water has been identified as a major health problem in Bangladesh. The Bangladesh Government, with international assistance, is attempting to mitigate the effects of arsenic by a major programme of tubewell water testing and education about arsenic and how its ingestion can be avoided. In early 2000 the first nationally representative cluster sample survey of water use in Bangladesh found that knowledge of arsenicosis remained low, tubewell water remained the dominant source of rural water, and few people knew if their tubewell was safe from arsenic contamination or alternatively treated it for arsenic. This paper reports on a follow‐up survey of the earlier study population to determine change over two years, and thus for the first time allows a measure of change at the national level. Awareness that there might be something wrong with tubewell water had risen markedly, especially among women respondents. However, there had been only a minor increase in the proportion reporting that they had changed water sources. This indicates a lack of a clear message about the risks involved, and about how to respond to the problem. The health authorities lack good information as to the real dangers involved, and the most appropriate interventions, both in technical terms and in terms of economic and social acceptability. In the absence of such information, the most effective strategy may be to promote more rapid testing of wells and to encourage people to switch wells. Copyright © 2005 John Wiley & Sons, Ltd.
Secondary metabolic changes in fibroblasts from six patients with hereditary lactic acidosis
Authors: Borud O. , Strømme J. H.
Published: June 2005

Studies on fibroblasts from patients with lactic acidosis of different causes showed secondary metabolic changes in pathways of glucose metabolism. These secondary changes may be important clues to the diagnosis of the many different types of hereditary lactic acidosis.
Combined deficiency of xanthine oxidase and sulphite oxidase: A defect of molybdenum metabolism or transport?
Authors: Duran M. , Beemer F. A. , v. d. Heiden C. , Korteland J. , de Bree P. K. , Brink M. , Wadman S. K. , Lombeck I.
Published: June 2005

A child is described who presented in the neonatal period with feeding difficulties, severe neurological abnormalities, lens dislocation of the eyes and dysmorphic symptoms of the head. Routine laboratory investigations revealed a decreased serum urate and a positive sulphite reaction of the urine. Subsequent chromatographic examinations showed xanthinuria and increased excretion ofS‐sulphocysteine and taurine to be present. In addition, high thiosulphate and low sulphate excretions in the urine were observed. Xanthine oxidase deficiency was demonstrated in a jejunal biopsy specimen, whereas the excretion of sulphur containing substances was considered to be characteristic of sulphite oxidase deficiency.

This new combination of defects may be the result of malfunctioning of both enzymes, possibly caused by alterations in the essential molybdenum containing active centre of the enzymes, which they share in common.
On the expressive power of CSP refinement
Authors: Roscoe A.W.
Published: June 2005

We show that wide-ranging classes of predicates on the failures-divergences model for CSP can be represented by refinement checks in a general form. These are predicates of a process
P
expressible as
F
(
P
)⊏
G
(
P
), where
F
and
G
are CSP contexts and ⊏ is refinement. We use ideas similar to full abstraction, but achieve a stronger property than that. Our main result is that topologically-closed predicates are precisely those representable when
F
and
G
are both uniformly continuous. We show that sub-classes of predicates such as refinement-closed and distributive ones are represented by special forms of this check.
The relationship between electric fields, conductances and currents in the high-latitude ionosphere: a statistical study using EISCAT data
Authors: Davies J. A. , Lester M.
Published: June 2005

Abstract. The relationship between electric fields, height-integrated conductivities and electric currents in the high-latitude nightside electrojet region is known to be complex. The tristatic nature of the EISCAT UHF radar facility provides an excellent means of exploring this interrelationship as it enables simultaneous estimates to be made of the full electric field vector and the ionospheric Hall and Pedersen conductances, further allowing the determination of both field-perpendicular electric current components. Over 1300 h of common programme observations by the UHF radar system provide the basis of a statistical study of electric fields, conductances and currents in the high-latitude ionosphere, from which preliminary results are presented. Times at which there is significant solar contribution to the ionospheric conductances have been excluded by limiting the observations according to solar zenith angle. Initial results indicate that, in general, the times of peak conductance, identified from the entire set of EISCAT observations, do not correspond to the times of the largest electric field values; the relative contribution of ionospheric conductance and electric field to the electrojet currents therefore depends critically on local time, a conclusion which corroborates work by previous authors. Simultaneous measurements confirm a tendency for a decrease in both Hall and Pedersen conductances to be accompanied by an increase in the electric field, at least for moderate and large electric field value, a tendency which is also identified to some extent in the ratio of the conductances, which acts as an indicator of the energy of precipitating particles.Key words. Ionosphere (auroral ionosphere; electric fields and currents)
On the nonlinear triggering of VLF emissions by power line harmonic radiation
Authors: Nunn D. , Manninen J. , Turunen T. , Trakhtengerts V. , Erokhin N.
Published: June 2005

Abstract. VLF ground data from Porojarvi in N. Finland has been presented. Spectrograms reveal frequent occurrence of power line harmonic radiation (PLHR), originating from the Finnish power system and from heavy industrial plant. The radiation is seen to penetrate the magnetosphere since numerous occurrences of PLHR triggered emissions are seen. Risers predominate but fallers and hooks are also observed. A well-established 1D Vlasov simulation code has been used to simulate these emissions, using plausible magnetospheric data for a range of L values from L = 4 to L = 5.5. The code is able to reproduce risers fallers and hooks in close agreement with observations. The results shed considerable insight into the generation structure of both risers and fallers.Key words. Electromagnetics (numerical methods) · Ionosphere (wave-particle interactions) · Magnetospheric physics (plasma waves and instabilities)
WIND observations of coherent electrostatic waves in the solar wind
Authors: Mangeney A. , Salem C. , Lacombe C. , Bougeret J.-L. , Perche C. , Manning R. , Kellogg P. J. , Goetz K. , Monson S. J. , Bosqued J.-M.
Published: June 2005

Abstract. The time domain sampler (TDS) experiment on WIND measures electric and magnetic wave forms with a sampling rate which reaches 120 000 points per second. We analyse here observations made in the solar wind near the Lagrange point L1. In the range of frequencies above the proton plasma frequency fpi and smaller than or of the order of the electron plasma frequency fpe, TDS observed three kinds of electrostatic (e.s.) waves: coherent wave packets of Langmuir waves with frequencies f ~ fpe, coherent wave packets with frequencies in the ion acoustic range fpi < f < fpe, and more or less isolated non-sinusoidal spikes lasting less than 1 ms. We confirm that the observed frequency of the low frequency (LF) ion acoustic wave packets is dominated by the Doppler effect: the wavelengths are short, 10 to 50 electron Debye lengths λD. The electric field in the isolated electrostatic structures (IES) and in the LF wave packets is more or less aligned with the solar wind magnetic field. Across the IES, which have a spatial width of the order of ~ 25λD, there is a small but finite electric potential drop, implying an average electric field generally directed away from the Sun. The IES wave forms, which have not been previously reported in the solar wind, are similar, although with a smaller amplitude, to the weak double layers observed in the auroral regions, and to the electrostatic solitary waves observed in other regions in the magnetosphere. We have also studied the solar wind conditions which favour the occurrence of the three kinds of waves: all these e.s. waves are observed more or less continuously in the whole solar wind (except in the densest regions where a parasite prevents the TDS observations). The type (wave packet or IES) of the observed LF waves is mainly determined by the proton temperature and by the direction of the magnetic field, which themselves depend on the latitude of WIND with respect to the heliospheric current sheet.Key words. Interplanetary physics (plasma waves and turbulence; solar wind plasma). Space plasma physics (electrostatic structures).