bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute and late morbidity in the treatment of advanced bladder carcinoma with accelerated radiotherapy, carbogen, and nicotinamide
Authors: Hoskin Peter J. , Rojas Ana M. , Phillips Heather , Saunders Michele I.
Published: April 2005

BACKGROUND

Accelerated radiotherapy combined with carbogen and nicotinamide (ARCON) to overcome tumor hypoxia and cell proliferation achieved high tumor control and survival in Phase II studies of patients with advanced head and neck and bladder carcinomas. Thus, morbidity and treatment outcomes from the latter study were analyzed to evaluate the therapeutic potential of ARCON.

METHODS

Acute and late morbidity was assessed in 105 patients with high‐grade superficial or muscle‐invasive bladder carcinoma who were given accelerated radiotherapy (50–55 grays in 4 weeks) with carbogen alone or with ARCON. Urinary dysfunction was scored based on daytime frequency, nocturia, incontinence, dysuria, hematuria, and urgency. Bowel morbidity was based on stool frequency and consistency, rectal discharge, blood loss, and medication. Endpoints for treatment outcome were overall survival, disease‐free survival, and locoregional control.

RESULTS

Nearly all patients experienced reduced ability to retain urine beyond 2 hours, although 20–30% had almost normal function at night. Incidence of acute moderate or worse dysuria was 41% with ARCON and 56% with carbogen; 96% and 76% of patients, respectively, had bowel frequencies ≥ 3 times per day. By 10–12 weeks from the start of radiotherapy, acute reactions returned to baseline levels. At 3 years, the daytime frequency ≤ 2 times per hour was ≈ 75% in both arms. Incidence of severe hematuria (≤ 25%) and urinary urgency (≤ 16%) was much lower. No more than 6% of patients had severe bowel morbidity. With most assays, the differences between schedules were not significant either for acute or late morbidity. Local tumor control and survival rates at 3 years were 53% and 43%, respectively, for ARCON, similar to the rates for carbogen alone.

CONCLUSIONS

Historical comparisons suggested no overt increase in normal tissue radiosensitivity when adding carbogen and nicotinamide. Although, for some endpoints, the incidence of late sequelae was higher than expected, overall morbidity was no worse than reported by others. The data indicated that ARCON could achieve a therapeutic gain in patients with advanced bladder carcinoma. A Phase III, randomized, multicenter trial is underway currently in the United Kingdom to evaluate these findings. Cancer 2005. © 2005 American Cancer Society.
Postnatal development of the cholinergic innervation in the dorsal hippocampus of rat: Quantitative light and electron microscopic immunocytochemical study
Authors: Aznavour Nicolas , Watkins Kenneth C. , Descarries Laurent
Published: April 2005

Choline acetyltransferase (ChAT) immunocytochemistry was used to examine the distribution and ultrastructural features of the acetylcholine (ACh) innervation in the dorsal hippocampus of postnatal rat. The length of ChAT‐immunostained axons was measured and the number of ChAT‐immunostained varicosities counted, in each layer of CA1, CA3, and dentate gyrus, at postnatal ages P8, P16, and P32. At P8, an elaborate network of varicose ChAT‐immunostained axons was already visible. At P16, the laminar distribution of this network resembled that in the adult, but adult densities were reached only by P32. Between P8 and P32, the mean densities for the three regions increased from 8.4 to 14 meters of axons and 2.3 to 5.7 million varicosities per cubic millimeter of tissue. At the three postnatal ages, the ultrastructural features of ChAT‐immunostained axon varicosities from the strata pyramidale and radiatum of CA1 were similar between layers and comparable to those in adult, except for an increasing frequency of mitochondria (up to 41% at P32). The proportion of these profiles displaying a synaptic junction was equally low at all ages, indicating an average synaptic incidence of 7% for whole varicosities, as previously found in adult. The observed junctions were small, usually symmetrical, and made mostly with dendritic branches. These results demonstrate the precocious and rapid maturation of the hippocampal cholinergic innervation and reveal its largely asynaptic nature as soon as it is formed. They emphasize the remarkable growth capacities of individual ACh neurons and substantiate a role for diffuse transmission by ACh during hippocampal development. J. Comp. Neurol. 486:61–75, 2005. © 2005 Wiley‐Liss, Inc.
Afferent projections to pharynx and soft palate motoneurons: A light and electron microscopical tracing study in the cat
Authors: Boers Jose , Hulshoff Antoinette C. , de Weerd Henk , Mouton Leonora J. , Kuipers Rutger , Holstege Gert
Published: April 2005

Pharynx and soft palate are muscles for respiration, vocalization, swallowing, and vomiting. In cat, motoneurons innervating pharynx/soft palate are located in the dorsal group of the nucleus ambiguus (dgNA) in the medulla oblongata. In cat, dgNA is the only part of nucleus ambiguus that can be distinguished as a separate cell group, which makes it possible to study its afferent input. In two cats, WGA‐HRP injections in dgNA and surrounding tegmentum resulted in retrogradely labeled cells at several levels of the neuraxis. In 170 cases anterograde tracers were injected in areas in which the cells of origin were identified. Results demonstrate that dgNA afferents originate from the tegmentum dorsolateral to the superior olivary complex, medullary ventromedial tegmentum, caudal raphe nuclei, medullary lateral tegmental field, nucleus retroambiguus (NRA), and adjoining tegmentum, extending into the first cervical segment of the spinal cord. In order to determine whether periaqueductal gray (PAG) and parabrachial nuclei (PB) make synaptic contacts with dgNA, ultrastructural studies combined anterograde tracing from PAG, PB, and NRA with retrograde tracing of pharyngeal and soft palate motoneurons. The results showed that PB, but not PAG, projects to the dgNA and that NRA afferent synapses are three times as numerous as those from PB. The morphology of PB and NRA synapses is consistent with excitatory input. In conclusion, pharyngeal and soft palate motoneurons receive their afferents almost exclusively from the pontine and medullary tegmentum and first cervical spinal segment. J. Comp. Neurol. 486:18–38, 2005. © 2005 Wiley‐Liss, Inc.
Withdrawal from progesterone increases expression of α4, β1, and δ GABAA receptor subunits in neurons in the periaqueductal gray matter in female Wistar rats
Authors: Griffiths Jenny , Lovick Thelma
Published: April 2005

Premenstrual dysphoric disorder (PMDD) shows comorbidity with other psychiatric conditions such as panic disorder (PD). The symptoms of both conditions are exacerbated during the late luteal phase of the menstrual cycle, when progesterone levels fall sharply. The present study investigated the effect of withdrawal from progesterone (PWD) on expression of α4, β1, and δ GABAA receptor subunits in neurons within the panic circuitry of the midbrain periaqueductal gray matter (PAG) in adult female Wistar rats. Immunostaining for α4, β1, and δ GABAA receptor subunits was present in neurons throughout the PAG in vehicle‐treated animals (VEH), in rats after 24 hours withdrawal from a progesterone dosing regime (PWD, 5 mg kg‐1 i.p. twice daily for 6 days), and in animals maintained on progesterone for 7 days (HP). Compared to HP and VEH animals, which did not differ significantly from each other, the number of immunostained neurons present in the PAG of PWD rats was significantly higher. The effect was most pronounced in the dorsolateral column of the PAG. The parallel changes in the three GABAA receptor subunits suggests that falling progesterone levels may be associated with expression of new receptors of the α4β1δ subtype. This could lead to functional changes in GABAergic transmission within the PAG. We suggest that changes in GABAA receptor‐mediated inhibitory tone in the PAG consequent to withdrawal from progesterone may contribute to the increased anxiety and susceptibility to panic seen during the late luteal phase of the menstrual cycle in PMDD and PD patients. J. Comp. Neurol. 486:89–97, 2005. © 2005 Wiley‐Liss, Inc.
Synthesis and characterization of dihydroxylammonium tetrachlorocuprate dihydrate crystals
Authors: Amirthaganesan G. , Kandhaswamy M. A. , Srinivasan V.
Published: April 2005

A new hydroxylammonium compound, [(NH3OH)2CuCl4], was synthesized and its crystals were grown at room temperature by slow evaporation of aqueous solutions. The crystals were characterized through powder XRD, thermogravimetry (TG), differential thermal analysis (DTA), low temperature differential scanning calorimetric (DSC) and FTIR spectra. The X‐ray powder diffraction confirms the crystallinity of the compound. A fitting decomposition pattern of the compound was formulated based on the TG and thereby confirming the formation of the compound in the stoichiometric ratio. The thermal anomalies occurring in the low temperature DSC indicate successive phase transitions. The low temperature phase transitions are attributed to the ordering of [NH3OH]+ ions. While most of the phase transitions are of first order type, the one occurring at –126 °C is of second order. Two glass transitions occur when the compound was cooled between –157.9 and –136.9 °C. The characteristic vibration bands due to [NH3OH]+ and CuCl ions are observed in the IR spectra. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
FT‐IR spectroscopic and thermal studies on pure and impurity added calcium tartrate tetrahydrate crystals
Authors: Sahaya Shajan X. , Mahadevan C.
Published: April 2005

Pure and impurity (strontium) added calcium tartrate tetrahydrate single crystals were grown by the gel method. The FT‐IR spectra of these crystals were recorded in the wavenumber range 400–4000 cm–1. The thermograms of the grown crystals were recorded in the temperature range 50–900 °C. FT‐IR spectra reveals the presence of water molecules, O‐H bond, C‐O and carbonyl C=O bonds. The thermograms show that these crystals are thermally unstable and decompose into its oxide through many stages. DTA curve of the pure crystal shows three endothermic and one exothermic peaks. (© 2005 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Development of directional‐coupler‐type sensor for printed circuits
Authors: Kurokawa Satoru , Sato Toru
Published: April 2005

As a sensor capable of identifying the direction of the signal propagating along a transmission line on a printed circuit board and the mismatch of the characteristic impedances and its location, a directional‐coupler sensor in a stripline configuration is conceived. The tested sensor can measure the direction of the electromagnetic wave and the mismatch location of the characteristic impedances along the transmission line, which has been difficult to do with magnetic or electric sensors. In this paper, physical shape of the sensor with the best directionality is derived by FDTD numerical calculations. Such a sensor is fabricated and its effectiveness is demonstrated. It is confirmed that the tested sensor has a directivity of more than 25 dB at frequencies below 6 GHz, and of more than 17 dB at frequencies below 7 GHz. © 2005 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 88(8): 41–49, 2005; Published online in Wiley InterScience (www.interscience. wiley.com). DOI 10.1002/ecja.10146
Impaired IL‐4 production by CD8+ T cells in NOD mice is related to a defect of c‐Maf binding to the IL‐4 promoter
Authors: Chen Xiao‐Ping , Falkner Dewayne H. , Morel Penelope A.
Published: April 2005

CD8+ T cells play an important role in the induction of the autoimmune response in non‐obese diabetic (NOD) mice. Here we describe abnormalities in the control of cytokine production by NOD CD8+ T cells. NOD CD8+ T cells had an increased propensity to produce IFN‐γ upon TCR activation, in both adult and 2‐week‐old mice. NOD CD8+ T cells had a reduced capacity to produce IL‐4 in type 2 conditions compared to CD8+ T cells from the diabetes‐resistant strains BALB/c and C57BL/6. Both GATA‐3 and c‐Maf, two positive transactivators for IL‐4 gene expression, were expressed in type 2 conditions at comparable levels in NOD CD8+ T cells. The GATA‐3 was functional since normal levels of IL‐5 were produced and the IL‐4 promoter was hyperacetylated in NOD CD8+ T cells. In contrast, c‐Maf failed to bind to its responsive element as determined by chromatin immunoprecipitation (ChIP) assay. These results suggest that NOD CD8+ T cells possess an increased propensity to produce IFN‐γ and impaired c‐Maf‐dependent DNA binding activities in vivo that lead to reduced IL‐4 production following TCR activation. These defects may facilitate the development of the autoimmune response by inducing an overall type 1‐biased immune response in NOD mice.
Toll‐like receptor‐dependent activation of several human blood cell types by protamine‐condensed mRNA
Authors: Scheel Birgit , Teufel Regina , Probst Jochen , Carralot Jean‐Philippe , Geginat Jens , Radsak Markus , Jarrossay David , Wagner Hermann , Jung Günther , Rammensee Hans‐Georg , Hoerr Ingmar , Pascolo Steve
Published: April 2005

We reported that RNA condensed on protamine is protected from RNase‐mediated degradation and can be used for vaccination. Here, we show that such complexes are also danger signals that activate mouse cells through a MyD88‐dependent pathway. Moreover, mRNA‐protamine complexes stimulate human blood cells. They strongly activate DC and monocytes, leading to TNF‐α and IFN‐α secretion. In addition, protamine‐RNA complexes directly activate B cells, NK cells and granulocytes. The detailed analysis of the activated cell types, the study of the cytokines released from PBMC cultured with protamine‐RNA complexes and recently published results suggest that TLR‐7 and TLR‐8 may be involved in the recognition of protamine‐stabilized RNA. Our data indicate that protamine‐stabilized RNA, which may be similar to RNA condensed in the nucleocapsids of RNA viruses, is a strong danger signal. Thus, similarly to plasmid DNA, protamine‐RNA combines antigen production and non‐specific immunostimulation. The studies presented here explain the capacity of protamine‐RNA to act as a vaccine, and pave the way towards the development of safe and efficient mRNA‐based immunotherapies.
Implication of allelic polymorphism of osteopontin in the development of lupus nephritis in MRL/lpr mice
Authors: Miyazaki Tatsuhiko , Ono Masao , Qu Wei‐Min , Zhang Ming‐Cai , Mori Shiro , Nakatsuru Shuichi , Nakamura Yusuke , Sawasaki Tatsuya , Endo Yaeta , Nose Masato
Published: April 2005

Potentially, autoimmune diseases develop from a combination of multiple genes with allelic polymorphisms. An MRL/Mp‐Faslpr/lpr (MRL/lpr) strain of mice develops autoimmune diseases, including lupus nephritis, but another lpr strain, C3H/HeJ‐Faslpr/lpr (C3H/lpr) does not. This indicates that MRL polymorphic genes are involved in the development of the diseases. By quantitative trait loci (QTL) analysis using 527 of the (MRL/lpr × C3H/lpr)F2 mice, we identified a novel locus for susceptibility to lupus nephritis at map position D5Mit115 on chromosome 5, the same alias of the osteopontin (Opn) gene (LOD score =4.0), susceptible in the MRL allele. In functional analyses of the MRL and C3H Opn alleles using synthetic osteopontin (OPN) made with a new method “cell‐free system” with wheat germ ribosomes, the MRL‐OPN induced higher expression and production of immunoglobulins as well as cytokines including TNF‐α, IL‐1β and IFN‐γ in splenocytes and/or macrophages than that of the C3H allele. These findings suggest that allelic polymorphism of OPN causes the functional differences in antibody production and macrophage activation between MRL and C3H strains, possibly involved in the development of lupus nephritis.
Systematic microanatomical analysis of CXCL13 and CCL21 in situ production and progressive lymphoid organization in rheumatoid synovitis
Authors: Manzo Antonio , Paoletti Samantha , Carulli Maresa , Blades Mark C. , Barone Francesca , Yanni Ghada , FitzGerald Oliver , Bresnihan Barry , Caporali Roberto , Montecucco Carlomaurizio , Uguccioni Mariagrazia , Pitzalis Costantino
Published: April 2005

CXCL13 and CCL21 have been functionally implicated in lymphoid tissue organization both in the upstream phases of lymphoid tissue embryogenesis and in ectopic lymphoid neogenesis in transgenic mice. Here, we analyzed the relationship between CXCL13 and CCL21 production and lymphoid tissue organization in rheumatoid synovitis as a model of a naturally occurring ectopic lymphoneogenesis. Through systematic analysis of mRNA and protein expression, we defined the microanatomical relationship between CXCL13 and CCL21 in progressive aggregational and structural phases of synovial inflammatory infiltrate. We provide the first direct in situ evidence that production of CXCL13 and CCL21 (rather than simply protein binding) is associated with inflammatory lymphoid tissue formation and development with the demonstration, in organized aggregates, of a secondary lymphoid organ‐like compartmentalization and vascular association. Notably, the presence of CXCL13 and CCL21 (protein and mRNA) was also demonstrated in non‐organized clusters and minor aggregational stages, providing evidence that their induction can take place independently and possibly upstream of T‐B compartmentalization, CD21+ follicular dendritic cell network differentiation and germinal center formation. Our data support the concept that, under inflammatory conditions, CXCL13 and CCL21 participate in lymphoid tissue microanatomical organization, attempting to recapitulate, in an aberrant lymphoid neogenetic process, their homeostatic and morphogenetic physiologic functions.
Humoral immune response to citrullinated collagen type II determinants in early rheumatoid arthritis
Authors: Burkhardt Harald , Sehnert Bettina , Bockermann Robert , Engström Åke , Kalden Jochen R. , Holmdahl Rikard
Published: April 2005

Collagen type II (CII) is a relevant joint‐specific autoantigen in the pathogenesis of rheumatoid arthritis (RA). Whereas the reasons for the breakage of self tolerance to this major cartilage component are still enigmatic, T cell responses to glycosylated CII determinants in RA patients indicate that post‐translational modifications play a role. Since the conversion of arginine into citrulline by peptidylarginine deiminases (PAD) in some non‐joint‐specific antigens such as filaggrin or fibrin has been shown to give rise to RA‐specific humoral immune responses, we investigated whether PAD modification of cartilage‐specific CII might affect its recognition by circulating autoantibodies in early RA. In vitro treatment with purified PAD led to arginine deimination of native CII or of synthetic CII peptides as evidenced by amino acid analysis. The citrullination resulted in modified recognition of the immunodominant CII epitope C1III (amino acid residues 359–369) by murine and human antibodies. In a cohort of early RA patients (n=286), IgG antibodies directed toward a synthetic citrullinated C1III peptide (citC1III‐P) were detectable with a prevalence of 40.4%. The partial autoantibody cross‐reactivity between citC1III‐P and citrullinated peptides mimicking epitopes of the cytoskeletal autoantigen filaggrin suggests that autoimmunity to cartilage‐specific modified self might be a critical intermediate bridging recognition of PAD‐modified extra‐articular autoantigens with the disruption of tolerance to native cartilage constituents.
Sediment transport in a highly regulated fluvial system during two consecutive floods (lower Ebro River, NE Iberian Peninsula)
Authors: Vericat Damia , Batalla Ramon J.
Published: April 2005

The transfer of sediment through a highly regulated large fluvial system (lower Ebro River) was analysed during two consecutive floods by means of sediment sampling. Suspended sediment and bedload transport were measured upstream and downstream of large reservoirs. The dams substantially altered flood timing, particularly the peaks, which were advanced downstream from the dams for flood control purposes. The suspended sediment yield upstream from the dams was 1 700 000 tonnes, which represented nearly 99 per cent of the total solid yield. The mean concentrations were close to 0·5 g l−1. The sediment yield downstream from the dams was an order of magnitude lower (173 000 tonnes), showing a mean concentration of 0·05 g l−1. The dams captured up to 95 per cent of the fine sediment carried in suspension in the river channel, preventing it from reaching the lowermost reaches of the river and the delta plain. Total bedload transport upstream from the dams was estimated to be about 25 000 tonnes, only 1·5 per cent of the total load. The median bedload rate was 100 gms−1. Below the dams, the river carried 178 000 tonnes, around 51 per cent of the total load, at a mean rate of 250 g ms−1. The results of sediment transport upstream and downstream from the large dams illustrate the magnitude of the sediment deficit in the lower Ebro River. The river mobilized a total of 350 000 tonnes in the downstream reaches, which were not replaced by sediment from upstream. Therefore, sediment was necessarily entrained from the riverbed and channel banks, causing a mean incision of 33 mm over the 27 km long study reach, altogether a significant step towards the long‐term degradation of the lower Ebro River. Copyright © 2005 John Wiley & Sons, Ltd.
Effect of rock fragment embedding on the aeolian deposition of dust on stone‐covered surfaces
Authors: Goossens Dirk
Published: April 2005

Many stone‐covered surfaces on Earth are subject to aeolian deposition of atmospheric dust. This study investigates how the deposition of dust is affected when rock fragments become gradually more embedded in the ground or, inversely, become more concentrated on the surface. Experiments were executed in an aeolian dust wind tunnel with eight different types of pebbles. The following parameters were measured: dust deposition on the pebbles, dust deposition between and underneath pebbles, total dust deposition (pebbles + inter‐pebble space), and the fraction, of total deposition, of dust caught by the pebbles alone. The absolute amount of dust deposition and the dust deposition density (dust deposition per unit surface) were studied for each parameter. The effects exerted by pebble size, pebble flattening, pebble elongation and wind speed were also investigated. Dust patterns on and around pebbles were also studied via flow visualization.

The absolute amount of dust settling on pebbles decreases the more that the pebbles become embedded. Dust deposition density on pebbles, on the other hand, increases with embedding. The more pebbles become embedded in the soil, the more efficient the process of dust deposition on pebbles becomes. Dust deposition between and underneath pebbles increases with pebble embedding. Dust deposition density between and underneath pebbles is maximum at 50 per cent embedding, showing that in this area dust deposition is most efficient when pebbles are halfway embedded. Total deposition slightly decreases the more pebbles become embedded, but total dust deposition density increases with embedding.

Aerodynamic flow separation and diverging and converging airflow play an important role in the process of dust deposition on stone‐covered surfaces. The more pebbles protrude above the soil, the more they act as an obstacle and the more they disturb the air and dust flow creating scouring zones, flow separation bubbles and shelter areas for the dust. All these effects diminish as pebbles become more embedded in the soil. However, perturbations in dust patterns remain visible until pebbles have disappeared entirely. Copyright © 2005 John Wiley & Sons, Ltd.
DEM resolution effects on shallow landslide hazard and soil redistribution modelling
Authors: Claessens L. , Heuvelink G. B. M. , Schoorl J. M. , Veldkamp A.
Published: April 2005

In this paper we analyse the effects of digital elevation model (DEM) resolution on the results of a model that simulates spatially explicit relative shallow landslide hazard and soil redistribution patterns and quantities. We analyse distributions of slope, specific catchment area and relative hazard for shallow landsliding for four different DEM resolutions (grid sizes of 10, 25, 50 and 100 m) of a 12 km2 study area in northern New Zealand. The effect of DEM resolution is especially pronounced for the boundary conditions determining a valid hazard calculation. For coarse resolutions, the smoothing effect results in a larger area becoming classified as unconditionally stable or unstable. We apply simple empirical soil redistribution algorithms for scenarios in which all sites with a certain landslide hazard fail and generate debris flow. The lower initial number of failing cells but also the inclusion of slope (limit) in those algorithms becomes apparent with coarser resolutions. For finer resolutions, much larger amounts of soil redistribution are found, which is attributed to the more detailed landscape representation. Looking at spatial patterns of landslide erosion and sedimentation, the size of the area affected by these processes also increases with finer resolutions. In general, landslide erosion occupies larger parts of the area than deposition, although the total amounts of soil material eroded and deposited are the same. Analysis of feedback mechanisms between soil failures over time shows that finer resolutions show higher percentages of the area with an increased or decreased landslide hazard. When the extent of sites with lower and higher hazards are compared, finer grid sizes and higher landslide hazard threshold scenarios tend to increase the total extent of areas becoming more stable relative to the less stable ones. Extreme care should be taken when quantifying landslide basin sediment yield by applying simple soil redistribution formulas to DEMs with different resolutions. Rather, quantities should be interpreted as relative amounts. For studying shallow landsliding over a longer timeframe, the ‘perfect’ DEM resolution may not exist, because no resolution can possibly represent the dimensions of all different slope failures scattered in space and time. We assert that the choice of DEM resolution, possibly restricted by data availability in the first place, should always be adapted to the context of a particular type of analysis. Copyright © 2005 John Wiley & Sons, Ltd.
Cytogenetic alterations in nonmelanoma skin cancer: A review
Authors: Ashton Kevin J. , Carless Melanie A. , Griffiths Lyn R.
Published: April 2005

Since the advent of cytogenetic analysis, knowledge about fundamental aspects of cancer biology has increased, allowing the processes of cancer development and progression to be more fully understood and appreciated. Classical cytogenetic analysis of solid tumors had been considered difficult, but new advances in culturing techniques and the addition of new cytogenetic technologies have enabled a more comprehensive analysis of chromosomal aberrations associated with solid tumors. Our purpose in this review is to discuss the cytogenetic findings on a number of nonmelanoma skin cancers, including squamous‐ and basal cell carcinomas, keratoacanthoma, squamous cell carcinoma in situ (Bowen's disease), and solar keratosis. Through classical cytogenetic techniques, as well as fluorescence‐based techniques such as fluorescence in situ hybridization and comparative genomic hybridization, numerous chromosomal alterations have been identified. These aberrations may aid in further defining the stages and classifications of nonmelanoma skin cancer and also may implicate chromosomal regions involved in progression and metastatic potential. This information, along with the development of newer technologies (including laser capture microdissection and comparative genomic hybridization arrays) that allow for more refined analysis, will continue to increase our knowledge about the role of chromosomal events at all stages of cancer development and progression and, more specifically, about how they are associated with nonmelanoma skin cancer. © 2005 Wiley‐Liss, Inc.
Detection of chromosomal imbalances in retinoblastoma by matrix‐based comparative genomic hybridization
Authors: Zielinski Boris , Gratias Sandrine , Toedt Grischa , Mendrzyk Frank , Stange Daniel E. , Radlwimmer Bernhard , Lohmann Dietmar R. , Lichter Peter
Published: April 2005

The genetic hallmark of retinoblastoma is mutation or deletion of the RB1 gene, whereas other genetic alterations that are also required are largely unknown. To screen for genomic imbalances on a genomewide level, we studied a series of 17 primary retinoblastomas by matrix‐based comparative genomic hybridization (matrix‐CGH). The matrix‐CGH chip contained 6,000 immobilized genomic DNA fragments covering the human genome, with an average resolution of about 500 kb. The most frequent imbalances detected were gains on chromosome arms 1q (12 of 17), 6p (10 of 17), 2p (5 of 17), and 19q (4 of 17) and loss on 16q (7 of 17). Candidate regions could be narrowed to small intervals by the identified minimally overlapping regions on 1q22, 1q32.1q32.2, 2p24.1, and 6p21.33–p21.31. Furthermore, two as‐yet‐unknown high‐level amplifications were detected, each in a single patient, on chromosome bands 1p34.2 and 1p33. Thus, this study identified new chromosomal regions and therefore potential candidate genes that may play a role in retinoblastoma. © 2005 Wiley‐Liss, Inc.
Intratumor versus intertumor heterogeneity in gene expression profiles of soft‐tissue sarcomas
Authors: Francis Princy , Fernebro Josefin , Edén Patrik , Laurell Anna , Rydholm Anders , Domanski Henryk A. , Breslin Thomas , Hegardt Cecilia , Borg Åke , Nilbert Mef
Published: April 2005

Soft‐tissue sarcomas (STSs) constitute more than 30 histologic entities. In addition, within each entity, tumors are often heterogeneous in macroscopic features, genetic alterations, microscopic appearance, and clinical course. Therefore, there has been concern about whether a single tumor sample can provide a gene expression profile representative of the entire tumor. We used 27‐k cDNA microarray slides to assess the importance of intratumor versus intertumor heterogeneity of the gene expression profiles of 2 morphologically heterogeneous STSs. Multiple pieces of tumor (8 and 10 pieces) were obtained from a myxoid variant of malignant fibrous histiocytoma (MFH) and a leiomyosarcoma (LMS), respectively, and the expression patterns were compared with single tumor samples from 20 MFHs and 16 LMSs. Hierarchical clustering analysis of the expression profiles showed that samples from the same tumor clustered together. The average intratumor distance was considerably shorter than the average intertumor distance in both LMS and MFH. In addition, tumor subclusters that distinguished different macroscopic parts of the tumor could be discerned. We concluded that intratumor variability exists but that accurate gene expression profiling also could be obtained using single samples from a large STS. © 2005 Wiley‐Liss, Inc.
Association testing with Mendel
Authors: Lange Kenneth , Sinsheimer Janet S. , Sobel Eric
Published: April 2005

This report presents an overview of association testing strategies from a user's perspective, with particular attention to the capabilities of the computer program Mendel. Association testing is driven by the nature of the study sample, the nature of the disease trait, and the kind of markers employed. The practicing statistician must also choose whether to conduct parametric or nonparametric tests. Because of the complexities involved, Mendel offers users several analysis options. The different options are tied together by shared input and output conventions and a shared language for defining models. Mendel also features new statistics and theory found in no other genetics software. The most important innovations include: association testing by penetrance estimation, expansion of matched‐pair designs to permutation unit designs, and a rigorous implementation of the measured genotype approach for quantitative trait loci. This report explains how Mendel imputes allele counts and conducts both asymptotic and permutation tests in the measured genotype framework. Genet. Epidemiol. © 2005 Wiley‐Liss, Inc.
Auditing after SOX: Some tips from the front lines
Authors: Smith Gordon
Published: April 2005

The Sarbanes‐Oxley Act (SOX) was the big event of last year. Auditors were scrambling to meet the deadline. It was a monumental effort. But how can we turn SOX to our advantage? The author, an auditing consultant, gives us some tips from the front lines in the ongoing battle to comply with SOX. What key questions should we be asking ourselves? How can we change the SOX process—a necessary but expensive headache— into a valuable business resource? © 2005 Gordon Smith of Canaudit, Inc.
In vitro validation of phase‐contrast flow measurements at 3 T in comparison to 1.5 T: Precision, accuracy, and signal‐to‐noise ratios
Authors: Lotz Joachim , Döker Rolf , Noeske Ralph , Schüttert Meike , Felix Roland , Galanski Michael , Gutberlet Matthias , Meyer Gerd Peter
Published: April 2005

Purpose

To evaluate the signal‐to‐noise ratio (SNR), precision, and accuracy of phase‐contrast flow measurements at 3 T with the help of an in vitro model and to compare the results with data from two 1.5‐T scanners.

Materials and Methods

Using an identical setup of a laminar flow model and sequence parameters, measurements were done at one 3‐T and at two 1.5‐T systems. Precision, accuracy, and SNR were obtained for velocity encodings ranging from 55 up to 550 cm−1. SNRs were calculated from the magnitude as well as the flow encoded images.

Results

Precision and accuracy for the in vitro flow model were similarly high in all scanners with no significant difference. For velocity encodings from 55 cm−1 up to 550 cm−1, the SNR in magnitude as well as phase encoded images of the 3‐T measurements was approximately 2.5 times higher than the SNR obtained from the two 1.5‐T systems.

Conclusion

Even without optimization for the 3‐T environment, flow measurements show the same high accuracy and precision as is known from clinical 1.5‐T scanners. The superior SNR at 3 T will allow further improvements in temporal and spatial resolution. This will be of interest for small‐size vessels like coronary arteries or for slow diastolic flow patterns. J. Magn. Reson. Imaging 2005;21:604–610. © 2005 Wiley‐Liss, Inc.
Magnetic resonance imaging of the upper abdomen using a free‐breathing T2‐weighted turbo spin echo sequence with navigator triggered prospective acquisition correction
Authors: Klessen Christian , Asbach Patrick , Kroencke Thomas J. , Fischer Thomas , Warmuth Carsten , Stemmer Alto , Hamm Bernd , Taupitz Matthias
Published: April 2005

Purpose

To evaluate a free‐breathing navigator triggered T2‐weighted turbo spin‐echo sequence with prospective acquisition correction (T2w‐PACE‐TSE) for MRI of the upper abdomen in comparison to a conventional T2‐weighted TSE (T2w‐CTSE), a single‐shot TSE (T2w‐HASTE), and a T1‐weighted gradient‐echo sequence (T1w‐FLASH).

Materials and Methods

A total of 40 consecutive patients were examined at 1.5 T using free‐breathing T2w‐PACE‐TSE, free‐breathing T2w‐CTSE, and breath‐hold T2w‐HASTE and T1w‐FLASH acquisition. Images were evaluated qualitatively by three radiologists regarding motion artifacts, liver‐spleen contrast, depiction of intrahepatic vessels, the pancreas and the adrenal glands, and overall image quality on a four‐point scale. Quantitative analysis of the liver‐spleen contrast was performed.

Results

Depiction and sharpness of intrahepatic vessels were rated significantly better (P < 0.01) using T2w‐PACE‐TSE compared to T2w‐CTSE and T2w‐HASTE sequences. Significantly higher contrast values were measured for T2w‐PACE‐TSE images compared to T2w‐CTSE, T2w‐HASTE, and T1w‐FLASH images (P < 0.01). Mean examination time of the T2w‐PACE‐TSE was 7.91 minutes, acquisition time of the T2w‐CTSE sequence was 4.52 minutes.

Conclusion

Prospective acquisition correction is an efficient method for reducing respiratory movement artifacts in T2w‐TSE imaging of the upper abdomen. Compared to T2w‐CTSE and T2w‐HASTE sequences recognition of anatomical details and contrast can be significantly improved. J. Magn. Reson. Imaging 2005;21:576–582. © 2005 Wiley‐Liss, Inc.
An MRI‐compatible semiautomated vacuum‐assisted breast biopsy system: Initial feasibility study
Authors: Daniel Bruce L. , Freeman Lynetta J. , Pyzoha Jessica M. , McCoy Terry D. , Birdwell Robyn L. , Bouley Donna M. , Movius Brennan , Hibner John A.
Published: April 2005

Purpose

To develop an MR‐compatible vacuum‐assisted core needle breast biopsy system.

Materials and Methods

A vacuum‐assisted breast biopsy system (Mammotome Hand Held; Ethicon Endo‐Surgery, USA) was modified for freehand MRI‐guided biopsy in an open, interventional 0.5‐T scanner (Signa SP; GE, USA). Probes (11 gauge [G]) were fabricated without significant susceptibility artifact. These mate with an electromechanical hand piece and control system that were modified for use within the MRI scanner. A total of 62 breast lesions were simulated in the mammary tissues of six recently lactating sows by injecting between 0.1 and 1.0 mL of an aqueous gel containing dilute gadopentetate dimeglumine (Gd‐DTPA) that formed a bright mass on T1‐weighted imaging.

Results

Mechanical performance was satisfactory. Magnetic susceptibility and radiofrequency (RF) artifacts from the 11‐G probe were negligible. T1‐weighted fast spin echo (FSE) was used to guide biopsy. Up to eight samples were removed per lesion. Overall, 461 samples were obtained in 493 attempts (94%). Sample weights averaged 54 mg (N = 493) compared to 4.6 mg (N = 24) from 14‐G titanium MRI‐compatible needles. On average, 59% of the attempted samples yielded target lesion material.

Conclusion

Preliminary results demonstrate the feasibility of a vacuum‐assisted breast biopsy system in the MRI environment. Small 0.1‐mL lesions can be biopsied without needle artifacts obscuring the target. J. Magn. Reson. Imaging 2005;21:637–644. © 2005 Wiley‐Liss, Inc.
Whole‐body MR angiography using a novel 32‐receiving‐channel MR system with surface coil technology: First clinical experience
Authors: Fenchel Michael , Requardt Martin , Tomaschko Katrin , Kramer Ulrich , Stauder Norbert I. , Naegele Thomas , Schlemmer Heinz‐Peter , Claussen Claus D. , Miller Stephan
Published: April 2005

Purpose

To demonstrate the feasibility of detecting atherosclerotic vascular disease using an innovative magnetic resonance angiography (MRA) protocol in combination with a dedicated whole‐body MR scanner with new surface coil technology.

Materials and Methods

A total of 10 volunteers and eight patients with peripheral arterial occlusive disease (PAOD) were examined at 1.5 T. Conventional digital subtraction angiography (DSA) of the symptomatic region was available as a reference standard in all eight patients. Depending on subjects' size, four to five three‐dimensional data sets were acquired using an adapted injection protocol. Images were assessed independently by two readers for vascular pathology. Additionally, signal‐to‐noise ratios (SNRs) and contrast‐to‐noise ratios (CNRs) were measured.

Results

Whole‐body MRA yielded excellent sensitivity and specificity of more than 95% for both readers with high interobserver agreement (k = 0.93). Surface coil signal reception rendered a high SNR (mean 151.28 ± 54.04) and CNR (mean 120.75 ± 46.47). Despite lower SNR and CNR of the cranial and cervical vessels, a two‐step injection protocol exhibited less venous superposition and therefore proved to be superior compared to single‐bolus injection.

Conclusion

Our approach provides accurate noninvasive high‐resolution imaging of systemic atherosclerotic disease, covering the arterial vasculature from intracranial arteries to distal runoff vessels. The recently introduced MR scanner and coil technology is feasible to significantly increase the performance of whole‐body MRA. J. Magn. Reson. Imaging 2005;21:596–603. © 2005 Wiley‐Liss, Inc.
Comparison of qualitative and quantitative measurements on unenhanced T1‐weighted fat saturation MR images in predicting pancreatic pathology
Authors: Gallix Benoît P. , Bret Patrice M. , Atri Mostafa , Lecesne Robin , Reinhold Caroline
Published: April 2005

Purpose

To evaluate the accuracy of signal intensity (SI) analysis on unenhanced fat‐suppressed T1‐weighted MR images in the diagnosis of pancreatic disease and to compare subjective interpretation with different quantitative measurements.

Materials and Methods

The pancreas was evaluated in 159 patients (86 normal and 73 with pancreatic disease) with spoiled gradient echo (GRE) T1‐weighted fat saturation MR images. The relative SI of the pancreas to liver and spleen was quantitatively measured using regions of interest (ROIs) and qualitatively assessed by two independent observers.

Results

The mean values between a normal and an abnormal pancreas with pancreas–liver ratios of 0.14 ± 0.37 vs. –0.32 ± 0.24, respectively, and pancreas–spleen ratios of 0.89 ± 0.55 vs. 0.02 ± 0.43, respectively, were significantly different (P < 0.001). The pancreas–liver SI ratio was significantly better than the pancreas–spleen ratio throughout the disease group (area under the receiver operating characteristic (ROC) curve ± SD; 0.92 ± 0.02 for pancreas–liver vs. 0.86 ± 0.03 for pancreas–spleen, P < 0.01), and after excluding cases of acute pancreatitis (0.96 ± 0.02 for pancreas–liver vs. 0.89 ± 0.03 for pancreas–spleen, P < 0.01). There was no statistically significant difference between quantitative and qualitative analysis (area under the ROC curve ± SD; 0.93 ± 0.02 vs. 0.93 ± 0.02 for the entire disease group; excluding acute pancreatitis 0.96 ± 0.02 vs 0.97 ± 0.02) for the diagnosis of pancreatic disease when using liver as internal standard. The interobserver concordance was very good (kappa > 0.71). The sensitivity of visual liver comparison was 80% in the entire disease group and 91% after the cases of acute pancreatitis were excluded, while specificity was 93%.

Conclusion

The pancreas–liver ratio is the best quantitative means of distinguishing normal from abnormal pancreas. Visual observation by experienced observers (qualitative measurement) was just as accurate as quantitative measurement. Detection of pancreatic pathology can be made with high accuracy by visually comparing the SI of the pancreas with that of the normal liver. J. Magn. Reson. Imaging 2005;21:583–589. © 2005 Wiley‐Liss, Inc.
Functional magnetic resonance imaging of the human lumbar spinal cord
Authors: Moffitt Michael A. , Dale Brian M. , Duerk Jeffrey L. , Grill Warren M.
Published: April 2005

Purpose

To determine whether consistent regions of activity could be observed in the lumbar spinal cord of single subjects with spin‐echo functional MRI (fMRI) if several repeated experiments were performed within a single imaging session.

Materials and Methods

Repeated fMRI experiments of the human lumbar spinal cord were performed at 1.5 T with a single‐shot spin‐echo technique (half‐Fourier single‐shot turbo spin‐echo (HASTE)) as used by previous investigators, and a modified method (fluid‐attenuated inversion recovery (FLAIR)‐HASTE) that nulled the otherwise highly variable signal from the cerebrospinal fluid (CSF).

Results

FLAIR‐HASTE reduced the variability of the signal in the CSF region to background levels, and presumably reduced associated artifacts in the spinal cord. Consistent areas of activation in the spinal cord in response to a thermal stimulus just below the knee were not observed across the fMRI experiments with either method.

Conclusion

FLAIR‐HASTE was useful for removing artifact in the spinal cord signal induced by variability in the CSF signal. However, with the techniques used in this study, we were not able to confirm the presence of a consistent fMRI response in the lumbar spinal cord because of the signal enhancement by extravascular protons (SEEP) effect during thermal stimulation of the hindlimb. J. Magn. Reson. Imaging 2005;21:527–535. © 2005 Wiley‐Liss, Inc.
An improved method for spinal functional MRI with large volume coverage of the spinal cord
Authors: Stroman Patrick W. , Kornelsen Jennifer , Lawrence Jane
Published: April 2005

Purpose

To develop a spinal functional MRI (fMRI) method with three‐dimensional coverage of a large extent of the spinal cord with minimal partial volume effects

Materials and Methods

fMRI data of the cervical spinal cord were obtained at 1.5 T with a single‐shot fast spin‐echo imaging method, from thin contiguous sagittal slices spanning the cord. Thermal stimulation was applied to the palm of the hand in a block pattern with 15°C for stimulation and 32°C during baseline periods. Prior to analysis, the image data at each time point were reformatted into three‐dimensional volumes and resliced perfectly transverse to the spinal cord. Smoothing was applied only in the superior‐inferior (S/I) direction across uniform tissue types. Active voxels were then identified by means of a correlation to a model paradigm.

Results

The resulting activity maps demonstrate activity primarily in ipsilateral sensory areas and in some motor areas, consistent with the spinal cord neuroanatomy. These data also demonstrate detail of the subsegmental organization of the spinal cord, as well as anatomical detail of the spinous processes and positions of nerve roots.

Conclusion

The spinal fMRI method described enables large volume coverage of the spinal cord in three dimensions, with reliable and reproducible results. J. Magn. Reson. Imaging 2005;21:520–526. © 2005 Wiley‐Liss, Inc.
Subtraction of in‐phase and opposed‐phase images in dynamic MR mammography
Authors: Reichenbach Jürgen R. , Hopfe Jens , Rauscher Alexander , Wurdinger Susanne , Kaiser Werner A.
Published: April 2005

Purpose

To develop and to evaluate an advanced image acquisition and analysis method for collecting T1‐weighted dynamic 3D MR mammography data sets by using a combined in‐phase (IP) and opposed‐phase (OP) imaging procedure.

Materials and Methods

3D MR mammography data sets were acquired by applying an interleaved gradient‐echo OP and IP imaging sequence during administration of contrast agent. A phantom data set, two volunteer breast data sets, and six patient breast data sets were recorded. Subtraction of dynamic in‐phase magnitude images was performed for clinical assessment. In addition, the magnitude subtraction (SIPOP) as well as the complex subtraction (cSIPOP) of the IP and OP magnitude and phase images were considered.

Results

The detection of small lesions, lesion boundaries, and tumor offshoots in fatty tissue was improved by the subtraction of IP and OP images without the risk of signal cancellation due to partial volume effects.

Conclusion

Dynamic MR mammography acquisition of IP and OP images in combination with appropriate data processing yields important supplementary information that can support routinely applied diagnostics of breast lesions that are fully embedded in fatty tissue by only marginally increasing acquisition time. J. Magn. Reson. Imaging 2005;21:565–575. © 2005 Wiley‐Liss, Inc.