bluuebunny/crossref_metadata_2025 huggingface dataset:
Do discharge codes underestimate hospitalisation due to heart failure? Validation study of hospital discharge coding for heart failure
Authors: Khand Aleem U. , Shaw Morag , Gemmel Islay , Cleland John G.F.
Published: July 2005

Background

Discharge codes are frequently used to describe hospital activity related to heart failure (HF).

Objectives

To determine whether discharge codes for HF underestimated or overestimated hospital activity related to HF.

Design

Patients with atrial fibrillation (AF), who commonly have HF, were identified and their case notes reviewed to identify cases of HF missed by discharge codes.

Participants and methods

Patients admitted between November 1997 and January 1998 with either HF or AF. Identification of HF and AF by ICD10 hospital discharge codes. Identification of additional cases of AF from a central hospital‐wide ECG database.

Results

We identified 330 cases with an ICD 10 code for HF, of which 43 (13%) were deemed to be miscoded, 32 patients (10%) were classified as possible, 39 (12%) as probable and 216 (65%) as definite HF. Results were similar whether or not HF was the primary discharge diagnosis. We identified 452 patients with AF, of whom 45 (10%) were classified as probable and 193 (43%) as definite HF. 129 (54%) of these cases had no diagnostic discharge code for HF. ICD 10 discharge codes for HF were correct in 77% of cases but identified only 66% of patients with probable or definite HF in this analysis. Screening of other diagnoses would have identified further cases of HF.

Conclusions

Hospital discharge codes substantially underestimate hospital events related to HF in the UK.
NosX function connects to nitrous oxide (N2O) reduction by affecting the CuZ center of NosZ and its activity in vivo
Authors: Wunsch Patrick , Körner Heinz , Neese Frank , van Spanning Rob J.M. , Kroneck Peter M.H. , Zumft Walter G.
Published: July 2005

The effect of loss of the 34‐kDa periplasmic NosX protein on the properties of N2O reductase was investigated with an N2O‐respiration negative, double mutant of the paralogous genes nosX and nirX of Paracoccus denitrificans. In spite of absence of whole‐cell N2O‐reducing activity, the purified reductase was catalytically active, which attributes NosX a physiological role in sustaining the reaction cycle. N2O reductase exhibited the spectroscopic features of CuA and the redox‐inert, paramagnetic state, , of the catalytic center. , hitherto considered the result of spontaneous reaction of the reductase with dioxygen, attains cellular significance.
Anticlericalism and Resistance: The Diocese of Huajuapam de León, 1930–1940
Authors: THOMAS SMITH BENJAMIN
Published: July 2005

This article looks at the response to government anticlericalism in the diocese of Huajuapam de León, Oaxaca. In particular it examines how the dynamic relationship between bishop, priests and parishioners established during the early twentieth century produced a religious culture, which wove itself into the cultural, ethnic, political and economic identities of the indigenous Mixtecs. This religious culture proved key to resistance to post-revolutionary anticlericalism and socialist education in the 1930s and led to the failure of the state project.
Public health implications of a case of haemolytic–uraemic syndrome associated with a concomitant outbreak of mild gastroenteritis in a small rural community
Authors: BUSANI L. , BOCCIA D. , CAPRIOLI A. , M. RUGGERI F. , MORABITO S. , MINELLI F. , LANA S. , RIZZONI G. , GIOFRÈ F. , MAZZEO M. , TOZZI A. E.
Published: July 2005

The concomitant occurrence of a case of haemolytic–uraemic syndrome (HUS) and 62 cases of mild gastroenteritis in schools of a small rural community in southern Italy induced the health authorities to suspect a foodborne outbreak of shiga-toxin-producing Escherichia coli (STEC) infection. The schools were closed and the catering service involved was investigated. However, STEC were not isolated from the HUS case or from the 56 cases of gastroenteritis examined, and the HUS case and the outbreak of gastroenteritis were probably just coincidental. A retrospective cohort study failed to show any correlation with consumption of school meals and suggested that the outbreak probably started outside the school setting and then spread within the schools by person-to-person transmission. All the cases examined were negative for common enteric pathogens and the responsible agent for the cases of gastroenteritis was not identified. The concern raised in the small community by the occurrence of a severe case of HUS and the lack of a rapid epidemiological assessment excluding the occurrence of a STEC outbreak, turned an epidemic episode of mild gastroenteritis into a public health emergency with relevant socioeconomic consequences. Prompt intervention in outbreaks following timely and effective risk communication are crucial for taking the most appropriate control measures and avoiding the spread of fear and panic in the community.
Trends in antimicrobial resistance phenotypes in non-typhoidSalmonellaefrom human and poultry origins in France
Authors: CAILHOL J. , LAILLER R. , BOUVET P. , LA VIEILLE S. , GAUCHARD F. , SANDERS P. , BRISABOIS A.
Published: July 2005

A total of 1873 strains from human origin and 4283 strains from non-human origin ofSalmonella entericaserotypes Typhimurium, Enteritidis, Heidelberg, Hadar and Virchow, collected over three years 1993, 1997 and 2000, were examined in order to determine the rate of antimicrobial resistance to 12 antimicrobial drugs. The objective of the study was to describe and to compare the evolution of the main resistance types in human and non-human isolates, focusing on the poultry sector. The evolution and the rates of antimicrobial resistances for the five serotypes, with the exception of Virchow, were almost comparable in strains isolated from human and non-human sources over the period studied. The most striking result concerning single resistance was the spectacular increase of the resistance frequency to nalidixic acid for the strains belonging to serotypes Hadar and Virchow, especially in the poultry food sector (14% in 1993vs. 72% in 2000 forSalmonellaVirchow, 4% in 1993vs. 70% in 2000 forSalmonellaHadar) and also in human isolates (24% in 1997vs. 48% in 2000 forS. Virchow, 31% in 1997vs. 78% in 2000 forS. Hadar). In addition to the classical resistance to ampicillin, streptomycin, sulphonamide, chloramphenicol and tetracycline (ASSuCT resistance type), which stabilized between 1997 and 2000, the emergence of a new resistance type was observed.
Land‐surface, boundary layer, and cloud‐field coupling over the southwestern Amazon in ERA‐40
Authors: Betts Alan K. , Viterbo Pedro
Published: July 2005

Models are powerful tools for understanding the coupling of physical processes. We illustrate this using averages from ERA‐40 for the Madeira River, a southwestern basin of the Amazon, which has a large seasonal cycle with a dry season in the austral winter. Daily‐mean land‐surface fluxes and state variables can be used to map the transitions of the surface “climate” of a model and to quantify the links between the soil moisture, the mean cloud‐base and cloud field, the shortwave and longwave radiation fields at the surface, the vertical motion field, the atmospheric precipitable water, and the surface precipitation. The links that are visible on a daily timescale can also be seen on the seasonal timescale. Several important surface processes are strongly influenced by soil moisture: relative humidity, which gives the mixed subcloud layer depth, low cloud cover, and the surface net long‐wave flux. The link between soil moisture and equivalent potential temperature can therefore be clearly seen once the temperature dependence is filtered. Surface evaporation is controlled as much by the feedback of the cloud field on the surface radiation budget as by soil moisture. Above the surface the cloud field and precipitation are coupled to the large‐scale dynamics, specifically the midtropospheric omega field. The shortwave cloud forcing of the atmosphere and the surface is given by the cloud field albedo at the top of the atmosphere to better than 1%. We have developed a new methodology for understanding the coupling and feedbacks between physical processes in models, so that different models can be compared with each other and with data.
Trajectory model sensitivity to differences in input data and vertical transport method
Authors: Harris Joyce M. , Draxler Roland R. , Oltmans Samuel J.
Published: July 2005

In this study, trajectory model sensitivity to the input meteorological data and vertical transport method is quantified. ERA‐40 and NCEP/NCAR reanalysis data sets are used to compare isentropic and kinematic 3‐D tropospheric trajectories. Expanding on previous trajectory sensitivity studies, we accumulate deviation statistics for an entire year and for three geographically diverse sites. The horizontal trajectory deviations are summarized as a percentage of average distance traveled. These results allow ranking from least to greatest among the five causes of trajectory uncertainty investigated here: minor differences in computational methodology, 3–4%; time interpolation, 9–25%; vertical transport method, 18–34%; meteorological input data, 30–40%; and combined two‐way differences in vertical transport method and meteorological input data, 39–47%. Although the deviations are somewhat dependent on starting location because of the influence of meteorology, at all three sites, 3‐D trajectories attained higher elevations and wind speeds than isentropic trajectories. In addition, deviation statistics for 3‐D trajectories exceeded those for isentropic trajectories. The reasons for this derive from uncertainties in the supplied vertical wind fields and the higher wind speeds in 3‐D trajectories on the one hand and the vertical constraints imposed by the isentropic assumption on the other.
Low degree spherical harmonic influences on Gravity Recovery and Climate Experiment (GRACE) water storage estimates
Authors: Chen J. L. , Rodell Matt , Wilson C. R. , Famiglietti J. S.
Published: July 2005

We estimate terrestrial water storage variations using time variable gravity changes observed by the Gravity Recovery and Climate Experiment (GRACE) satellites during the first 2 years of the mission. We examine how treatment of low‐degree gravitational changes and geocenter variations affect GRACE based estimates of basin‐scale water storage changes, using independently derived low‐degree harmonics from Earth rotation (EOP) and satellite laser ranging (SLR) observations. GRACE based water storage changes are compared with estimates from NASA's Global Land Data Assimilation System (GLDAS). Results from the 22 GRACE monthly gravity solutions, covering the period April 2002 to July 2004, show remarkably good agreement with GLDAS in the Mississippi, Amazon, Ganges, Ob, Zambezi, and Victoria basins. Combining GRACE observations with EOP and SLR degree‐2 spherical harmonic coefficient changes and SLR observed geocenter variations significantly affects and apparently improves the estimates, especially in the Mississippi, Ob, and Victoria basins.
New surface temperature analyses for climate monitoring
Authors: Smith Thomas M. , Peterson Thomas C. , Lawrimore Jay H. , Reynolds Richard W.
Published: July 2005

Global surface temperature is a critical measure of climate variation. Here the averages of a new surface‐temperature analysis are compared to an estimate of the global average which has been used for monitoring surface‐temperature variations at NOAA's National Climatic Data Center (NCDC) since 1998. As a replacement to the existing method, this new analysis uses improved methods that provide error estimates as well as the ability to perform analyses on finer spatial scales. Comparisons show only minor global‐average differences, and the two estimates indicate essentially the same trend over the historical record, beginning in 1880. The two are most similar after about 1970, a period with a large change in the global‐average temperature. The uncertainty estimates computed here account for changes in sampling and for systematic bias uncertainties. The means of the different analyses generally fall within the uncertainty estimates. The uncertainty computed here indicates that anomalies in the 19th century may not be significant, but the 20th century trends are significant.
Air separation by single wall carbon nanotubes: Thermodynamics and adsorptive selectivity
Authors: Arora Gaurav , Sandler Stanley I.
Published: July 2005

Separation of a nitrogen–oxygen mixture (air) by single wall carbon nanotubes has been studied using grand canonical Monte Carlo simulations at a range of nanotube diameters, temperatures, and pressures. It is demonstrated that depending on these operating parameters, the extent of adsorptive selectivity can vary significantly. Detailed calculations are also presented for the adsorption isotherms, energies, and isosteric heats of pure nitrogen, oxygen, and their mixture at 100K in a carbon nanotube of 12.53-Å diameter. In single-component simulations, it is found that near saturation loading nitrogen forms only an annular layer close to the nanotube wall, while smaller-sized oxygen also occupies the region near the center of the nanotube. In mixture adsorption, the energetically favored nitrogen is preferentially adsorbed at low loadings. However, at high loadings oxygen replaces nitrogen due to the dominant entropic effects, and therefore a high selectivity towards oxygen is observed close to the saturation loading. The effect of the entropic change on mixture adsorption is evident from the calculated isosteric heats of adsorption. The mixture isotherms obtained from simulations are found to be in good agreement with the predictions based only on the pure component simulation results.
Dynamics of self-adjusting systems with noise
Authors: Melby Paul , Weber Nicholas , Hübler Alfred
Published: July 2005

We study several self-adjusting systems with noise. In our analytical and numerical studies, we find that the dynamics of the self-adjusting parameter can be accurately described with a rescaled diffusion equation. We find that adaptation to the edge of chaos, a feature previously ascribed to self-adjusting systems, is only a long-lived transient when noise is present in the system. In addition, using analytical, numerical, and experimental methods, we find that noise can cause chaotic outbreaks where the parameter reenters the chaotic regime and the system dynamics become chaotic. We find that these chaotic outbreaks have a power law distribution in length.
Luminescence spectroscopy of matrix-isolated atomic manganese: Excitation of the “forbidden” aDJ6↔aS6 transitions
Authors: Collier Martin A. , Ryan Maryanne C. , McCaffrey John G.
Published: July 2005

Laser-induced excitation spectra recorded for the electric-quadrupole 3d64saDJ6←3d54s2aS5∕26 transitions of atomic Mn, allow assignment of the red emission features, previously observed in Mn/RG (RG=Ar, Kr and Xe) matrices with resonance 3d54s4pzP5∕26←3d54s2aS5∕26 excitation, to the metastable aD9∕26 state. Narrow excitation bands recorded for the red site in the Mn∕Kr system allow identification of all five spin-orbit levels (J=1∕2, 3∕2, 5∕2, 7∕2 and 9∕2) in the aD6 state. The coincidence of the lowest energy excitation band and the observed 585.75nm (17072cm−1) emission band of atomic Mn in Kr matrices, yielded a definitive assignment of this emission to a transition from the J=9∕2 spin-orbit level. Temperature dependent emission scans lead to the identification of the zero phonon line for the aD9∕26→aS5∕26 transition at 585.75nm. The identified matrix-shift of +20cm−1 allows an assessment of the extent of the ground state stabilization in the red (2°) site of atomic Mn isolation in solid Kr. Emission produced with direct aD6 state excitation yielded both the 585.75 and 626nm features. The former band arises for Mn atoms occupying the red site—the latter from blue site occupancy in solid Kr. The excitation linewidths recorded for these two sites differ greatly, with the blue site yielding a broad featureless profile, in contrast to the narrow, structured features of the red site. The corresponding red site aDJ6↔aS5∕26 transitions in Ar and Xe matrices are broader than in Kr—a difference considered to originate from the site sizes available in these hosts and the interatomic Mn∙RG potentials. The millisecond decay times recorded for the red emission bands in the Mn/RG systems are all much shorter than the 3s value predicted for the gas phase aD9∕26→aS5∕26 transition. This enhancement allows optical pumping of the forbidden aDJ6↔aS6 transitions with low laser powers when atomic manganese is isolated in the solid state. However all the emission decays are complex, exhibiting triple exponential decays. This behavior may be related to the dependence of the excitation linewidths on the J value, indicating removal of the J degeneracy due to weak matrix-induced, crystal field splitting.
A comparison of fine structures in high-resolution x-ray-absorption spectra of various condensed organic molecules
Authors: Schoell A. , Zou Y. , Huebner D. , Urquhart S. G. , Schmidt Th. , Fink R. , Umbach E.
Published: July 2005

We report on a high-resolution C–K and O–K near-edge x-ray-absorption fine-structure (NEXAFS) study of large aromatic molecules in condensed thin films, namely, anhydrides 1,4,5,8-naphthalene-tetracarboxylic acid dianhydride, 3,4,9,10-perylene-tetracarboxylic acid dianhydride, benzoperylene-(1,2)-dicarboxylic acid anhydride, and 1,8-naphthalene-dicarboxylic acid anhydride and the quinoic acenaphthenequinone. Due to the high-energy resolution of the third-generation synchrotron source BESSY II we observe large differences in the NEXAFS fine structures even for very similar molecules, resulting in a wealth of new information. The rich fine structure can unambiguously be assigned to the coupling of electronic transitions to vibronic excitations. Backed by ab initio calculations we present a detailed analysis of the spectra that allows the complete interpretation of the near-edge features. It also yields information on the vibronic properties in the electronically excited state as well as on the response of the electronic system upon core excitation. The strong differences in the electron-vibron coupling for different molecules are discussed.
Neumann series and lattice sums
Authors: McPhedran R. C. , Nicorovici N. A. , Botten L. C.
Published: July 2005

We consider sums over the square lattice which depend only on radial distance, and provide formulas which enable sums of functions with Neumann series to be reexpressed as combinations of hypergeometric series. We illustrate the procedure using trigonometric sums previously studied by Borwein and Borwein, sums combining logarithms, Bessel functions Jλ, and powers of distance, and sums of Neumann functions. We also exhibit sums which may be evaluated analytically and recurrence formulas linking sums.
Effective hole injection of organic light-emitting diodes by introducing buckminsterfullerene on the indium tin oxide anode
Authors: Hong Il-Hwa , Lee Min-Woo , Koo Young-Mo , Jeong Hyein , Kim Tae-Shick , Song Ok-Keun
Published: July 2005

We demonstrate that dramatically improved hole injection can be achieved by inserting a very thin C60 film between the indium tin oxide (ITO) electrode and N,N′-diphenyl-N,N′-bis(1,1′-biphenyl)-4,4′-diamine (NPB) layer. This result is ascribed to the formation of an interfacial dipole layer of buckminsterfullerene (C60) on the ITO electrode. The dipole layer induces the surface potential shift that contributes to improve the charge injection efficiency. The chemical shift was downward to help lower the hole injection energy barrier from the ITO electrode to the NPB layer, consistent with the moderately strong electron accepting nature of C60. The enhanced-charge injection provides a simple way of reducing the power consumption of organic electronic devices for real applications.
Push-pull mode magnetostrictive/piezoelectric laminate composite with an enhanced magnetoelectric voltage coefficient
Authors: Dong Shuxiang , Zhai Jungyi , Bai Feiming , Li Jie-Fang , Viehland D.
Published: July 2005

A magnetoelectric (ME) laminate composite consisting of a symmetric longitudinally poled piezoelectric Pb(Mg1∕3Nb2∕3)O3–PbTiO3 crystal and two longitudinally magnetized magnetostrictive Tb1−xDyxFe2 layers has been developed that has a notably superior ME voltage coefficient, relative to previous laminate configurations. The symmetric nature of the longitudinally poled piezoelectric layer allows for operation in a push-pull mode that optimizes elastic coupling between layers. Our small laminate has a giant ME voltage coefficient of ∼1.6V∕Oe at low frequencies, a significant enhancement of this coefficient to ∼20V∕Oe under resonance drive, and an exceptional low-level magnetic field sensitivity of ∼10−12T at f=f0.
Ultraviolet emission from layered nanocomposites of Zn(OH)2 and sodium dodecyl sulfate prepared by laser ablation in liquid
Authors: Usui Hiroyuki , Sasaki Takeshi , Koshizaki Naoto
Published: July 2005

We investigated the optical properties of Zn nanocomposites with the lamellar structure of sodium dodecyl sulfate (SDS) molecules prepared by laser ablation in an SDS aqueous solution. The absorption band of the nanocomposites was found at the same wavelength as that of ZnO (370nm). The peak positions of the nanocomposites in the photoluminescence and excitation spectra were almost the same as those of ZnO. This coincidence implies that the ZnO electronic structure was partially formed in the nanocomposites. Two structural possibilities were discussed for the nanocomposites.
Fe nanocrystal growth on SrTiO3(001)
Authors: Silly Fabien , Castell Martin R.
Published: July 2005

We have investigated the structure and morphology of self-assembled iron nanocrystals supported on a SrTiO3(001)-c(4×2) substrate using scanning tunneling microscopy. Nanocrystals with a truncated pyramid shape were imaged, which result from the epitaxial growth of bcc Fe on SrTiO3(001). By using the dimensions of the nanocrystal facets at equilibrium and an energy minimization calculation, we obtain the adhesion energy γadh=(3.05±0.15)J∕m2 for bcc Fe on SrTiO3(001)-c(4×2).
Asynchronous optical sampling terahertz time-domain spectroscopy for ultrahigh spectral resolution and rapid data acquisition
Authors: Yasui Takeshi , Saneyoshi Eisuke , Araki Tsutomu
Published: July 2005

We propose a terahertz time-domain spectrometer based on asynchronous optical sampling. The spectrometer features ultrahigh spectral resolution equivalent to a laser mode-locked frequency and rapid data acquisition. The proposed method requires no mechanical translation stages for time-delay scanning, and hence, overcomes the inherent tradeoff between frequency resolution and data acquisition time. Time evolution of the picosecond terahertz pulse with a temporal window of 12.1 ns is measured directly on an oscilloscope using a time-scale magnification of 764 815. A frequency resolution of 82.6 MHz is achieved at a measurement time of 10 s. The effectiveness of the proposed method is confirmed by comparing it with conventional stage-scanning terahertz time-domain spectroscopy.
Friction transfer deposition of ordered conjugated polymer nanowires and transistor fabrication
Authors: Li S. P. , Newsome C. J. , Russell D. M. , Kugler T. , Ishida M. , Shimoda T.
Published: July 2005

Monodisperse, ordered conjugated polymer nanowires were deposited by friction-transfer technique. Films that comprise such ordered polymer nanowires show a strong optical and electronic anisotropy due to the high compaction of molecule chains in the individual nanowires. Field-effect transistors that were fabricated using poly[9,9-dioctylfluorene-co-bithiophene(F8T2)] nanowires exhibit a field-effect mobility of 3.5×10−2cm2V−1s−1 along the wire direction, which is much higher than the mobility value (5×10−3cm2V−1s−1) obtained in transistors with spin-coated F8T2.
Effects of lamb age, hormone stimulation and response to hormone stimulation on the yield and in vitro developmental competence of prepubertal lamb oocytes
Authors: Morton Katherine M. , Catt Sally L. , Maxwell W. M. Chis , Evans Gareth
Published: July 2005

Experiments were conducted to determine the effects of lamb age, hormone stimulation (Experiment 1) and response to stimulation (Experiment 2) on the in vitro production of embryos from prepubertal lambs aged 3–4 and 6–7 weeks of age. For 3–4-week-old lambs, hormone stimulation increased the number of follicles (29.9 ± 15.3 v. 70.6 ± 8.2), oocytes per ovary (18.3 ± 6.3 v. 39.3 ± 5.8) and oocyte development to the blastocyst stage (0/192 (0.0%) v. 115/661 (17.4%); P < 0.05). Lamb age (3–4 v. 6–7 weeks old) increased oocyte development to the blastocyst stage (115/661 (17.4%) v. 120/562 (21.4%) respectively). In Experiment 2, hormone-stimulated lambs (3–4 and 6–7 weeks old) were divided into low, medium or high responders based on the number of ovarian follicles (<20, 20–50 and >100 follicles per ovary respectively). The response to hormone stimulation did not affect oocyte recovery rate, but the number of oocytes suitable for culture was increased for high-responding 3–4-week-old lambs only (P < 0.05). Oocyte development to the blastocyst stage was not affected by response to stimulation for 3–4-week-old lambs (15.2–25.6%; P > 0.05), but was reduced for high (6.7%) compared with low (19.5%) and medium (30.9%) responding 6–7-week-old lambs (P < 0.05). These results demonstrate that the production of embryos from prepubertal lambs is increased by hormone stimulation and lamb age and the response to stimulation does not affect embryo production from 3–4-week-old lambs, although by 6–7 weeks of age a high response to stimulation reduces blastocyst formation.
Inositol transport in mouse embryonic stem cells
Authors: Higgins B. D. , Kane M. T.
Published: July 2005

The uptake of myo-inositol by mouse embryonic stem (ES) cells was measured using [2-3H]myo-inositol. Uptake of myo-inositol by ES cells occurred in a mainly saturable, sodium-, time- and temperature-dependent manner, which was inhibited by glucose, phloridzin and ouabain. Self inhibition by inositol was much greater than inhibition by glucose indicating that transport was not occurring via a sodium-dependent glucose transporter. Uptake rate was much greater than efflux rate indicating a mainly unidirectional transport mechanism. Estimated kinetics parameters for sodium-dependent inositol uptake were a Km of 65.1 ± 11.8 μ mol L−1 and a Vmax of 5.0 ± 0.59 pmol μ g protein−1 h−1. Inositol uptake was also sensitive to osmolality; uptake increased in response to incubation in hypertonic medium indicating a possible role for inositol as an osmolyte in ES cells. These characteristics indicate that myo-inositol transport in mouse ES cells occurs by a sodium-dependent myo-inositol transporter protein.
Murine malaria parasite sequestration: CD36 is the major receptor, but cerebral pathology is unlinked to sequestration
Authors: Franke-Fayard Blandine , Janse Chris J. , Cunha-Rodrigues Margarida , Ramesar Jai , Büscher Philippe , Que Ivo , Löwik Clemens , Voshol Peter J. , den Boer Marion A. M. , van Duinen Sjoerd G. , Febbraio Maria , Mota Maria M. , Waters Andrew P.
Published: July 2005

Sequestration of malaria-parasite-infected erythrocytes in the microvasculature of organs is thought to be a significant cause of pathology. Cerebral malaria (CM) is a major complication of
Plasmodium falciparum
infections, and PfEMP1-mediated sequestration of infected red blood cells has been considered to be the major feature leading to CM-related pathology. We report a system for the real-time
in vivo
imaging of sequestration using transgenic luciferase-expressing parasites of the rodent malaria parasite
Plasmodium berghei.
These studies revealed that: (
i
) as expected, lung tissue is a major site, but, unexpectedly, adipose tissue contributes significantly to sequestration, and (
ii
) the class II scavenger-receptor CD36 to which PfEMP1 can bind is also the major receptor for
P. berghei
sequestration, indicating a role for alternative parasite ligands, because orthologues of PfEMP1 are absent from rodent malaria parasites, and, importantly, (
iii
) cerebral complications still develop in the absence of CD36-mediated sequestration, dissociating parasite sequestration from CM-associated pathology. Real-time
in vivo
imaging of parasitic processes may be used to evaluate the molecular basis of pathology and develop strategies to prevent pathology.
Organically modified silica nanoparticles: A nonviral vector for
in vivo
gene delivery and expression in the brain
Authors: Bharali Dhruba J. , Klejbor Ilona , Stachowiak Ewa K. , Dutta Purnendu , Roy Indrajit , Kaur Navjot , Bergey Earl J. , Prasad Paras N. , Stachowiak Michal K.
Published: July 2005

This article reports on the application of organically modified silica (ORMOSIL) nanoparticles as a nonviral vector for efficient
in vivo
gene delivery. Highly monodispersed, stable aqueous suspension of nanoparticles, surface-functionalized with amino groups for binding of DNA, were prepared and characterized. Stereotaxic injections of nanoparticles, complexed with plasmid DNA encoding for EGFP, into the mouse ventral midbrain and into lateral ventricle, allowed us to fluorescently visualize the extensive transfection of neuronal-like cells in substantia nigra and areas surrounding the lateral ventricle. No ORMOSIL-based toxicity was observed 4 weeks after transfection. The efficiency of transfection equaled or exceeded that obtained in studies using a viral vector. An
in vivo
optical imaging technique (a fiber-based confocal fluorescent imaging system) provided an effective means to show the retention of viability of the transfected cells. The ORMOSIL-mediated transfections also were used to manipulate the biology of the neural stem/progenitor cells
in vivo
. Transfection of a plasmid expressing the nucleus-targeting fibroblast growth factor receptor type 1 resulted in significant inhibition of the
in vivo
incorporation of bromodeoxyuridine into the DNA of the cells in the subventricular zone and the adjacent rostral migratory stream. This
in vivo
approach shows that the nuclear receptor can control the proliferation of the stem/progenitor cells in this region of the brain. The results of this nanomedicine approach using ORMOSIL nanoparticles as a nonviral gene delivery platform have a promising future direction for effective therapeutic manipulation of the neural stem/progenitor cells as well as
in vivo
targeted brain therapy.
A TRPM7 variant shows altered sensitivity to magnesium that may contribute to the pathogenesis of two Guamanian neurodegenerative disorders
Authors: Hermosura Meredith C. , Nayakanti Hannah , Dorovkov Maxim V. , Calderon Fernanda R. , Ryazanov Alexey G. , Haymer David S. , Garruto Ralph M.
Published: July 2005

Guamanian amyotrophic lateral sclerosis (ALS-G) and parkinsonism dementia (PD-G) have been epidemiologically linked to an environment severely deficient in calcium (Ca
2+
) and magnesium (Mg
2+
). Transient receptor potential melastatin 7 (TRPM7) is a bifunctional protein containing both channel and kinase domains that has been proposed to be involved in the homeostatic regulation of intracellular Ca
2+
, Mg
2+
, and trace metal ion concentration. There is evidence that TRPM7 is constitutively active and that the number of available channels is dependent on intracellular free Mg
2+
levels. We found a
TRPM7
variant in a subset of ALS-G and PD-G patients that produces a protein with a missense mutation, T1482I. Recombinant T1482I TRPM7 exhibits the same kinase catalytic activity as WT TRPM7. However, heterologously expressed T1482I TRPM7 produces functional channels that show an increased sensitivity to inhibition by intracellular Mg
2+
. Because the incidence of ALS-G and PD-G has been associated with prolonged exposure to an environment severely deficient in Ca
2+
and Mg
2+
, we propose that this variant
TRPM7
allele confers a susceptibility genotype in such an environment. This study represents an initial attempt to address the important issue of gene–environment interactions in the etiology of these diseases.
Experimental trial for diagnosis of pancreatic ductal carcinoma based on gene expression profiles of pancreatic ductal cells
Authors: Ishikawa Madoka , Yoshida Koji , Yamashita Yoshihiro , Ota Jun , Takada Shuji , Kisanuki Hiroyuki , Koinuma Koji , Choi Young Lim , Kaneda Ruri , Iwao Toshiyasu , Tamada Kiichi , Sugano Kentaro , Mano Hiroyuki
Published: July 2005

Pancreatic ductal carcinoma (PDC) remains one of the most intractable human malignancies, mainly because of the lack of sensitive detection methods. Although gene expression profiling by DNA microarray analysis is a promising tool for the development of such detection systems, a simple comparison of pancreatic tissues may yield misleading data that reflect only differences in cellular composition. To directly compare PDC cells with normal pancreatic ductal cells, we purified MUC1‐positive epithelial cells from the pancreatic juices of 25 individuals with a normal pancreas and 24 patients with PDC. The gene expression profiles of these 49 specimens were determined with DNA microarrays containing >44 000 probe sets. Application of both Welch's analysis of variance and effect size‐based selection to the expression data resulted in the identification of 21 probe sets corresponding to 20 genes whose expression was highly associated with clinical diagnosis. Furthermore, correspondence analysis and 3‐D projection with these probe sets resulted in separation of the transcriptomes of pancreatic ductal cells into distinct but overlapping spaces corresponding to the two clinical classes. To establish an accurate transcriptome‐based diagnosis system for PDC, we applied supervised class prediction algorithms to our large data set. With the expression profiles of only five predictor genes, the weighted vote method diagnosed the class of samples with an accuracy of 81.6%. Microarray analysis with purified pancreatic ductal cells has thus provided a basis for the development of a sensitive method for the detection of PDC. (Cancer Sci 2005; 96: 387–393)
Inhibitory effect of a selective cyclooxygenase inhibitor on the invasion‐stimulating activity of orthotopic fibroblasts for scirrhous gastric cancer cells
Authors: Tendo Masashige , Yashiro Masakazu , Nakazawa Kazunori , Yamada Nobuya , Hirakawa Kosei
Published: July 2005

The cyclooxygenase (COX)‐2 inhibitor has been reported to impede the progression of gastric cancer, but underlying mechanisms remain unclear. We therefore investigated the effect of a COX‐2 inhibitor, JTE‐522, on the ability of orthotopic fibroblasts to stimulate invasion of scirrhous gastric carcinoma cells. The human scirrhous gastric cancer cell lines OCUM‐2D or OCUM‐2M, and human gastric fibroblasts (NF‐21) were cultured in the absence or presence of JTE‐522 at various concentrations. Cancer cells were then assayed for invasiveness in vitro by invasion assay. The effect of prostaglandins (PG) on growth factor production in NF‐21 cells was examined by ELISA. Finally, the effects of orally administrated JTE‐522 on orthotopically transplanted tumors were examined in nude mice. NF‐21 cells stimulated invasion by OCUM‐2D cells, an effect suppressed by JTE‐522 at 5 × 10−6 M. Hepatocyte growth factor (HGF) and PGE2 production by NF‐21 cells were suppressed by JTE‐522 (P < 0.01). PGE2 stimulated HGF production by NF‐21 cells in a dose‐dependent manner. JTE‐522 significantly suppressed orthotopic tumor growth and lymph node metastasis, and also decreased HGF expression by fibroblasts within the gastric tumor. In conclusion, we found that gastric fibroblasts stimulated invasiveness in scirrhous gastric cancer cells, whereas a selective COX‐2 inhibitor inhibited this paracrine effect by decreasing fibroblast PGE2 production, resulting in downregulation of HGF production. (Cancer Sci 2005; 96: 451–455)
Does concurrent prescription of selective serotonin reuptake inhibitors and non‐steroidal anti‐inflammatory drugs substantially increase the risk of upper gastrointestinal bleeding?
Authors: TATA L. J. , FORTUN P. J. , HUBBARD R. B. , SMEETH L. , HAWKEY C. J. , SMITH C. J. P. , WHITAKER H. J. , FARRINGTON C. P. , CARD T. R. , WEST J.
Published: July 2005

Background:  A 15‐fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non‐steroidal anti‐inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people.

Aim:  To quantify the risk of gastrointestinal bleeding associated with current exposure to non‐steroidal anti‐inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently.

Methods:  We conducted a case–control analysis of 11 261 cases with upper gastrointestinal bleeding and 53 156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self‐controlled case series analysis.

Results:  Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08–2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02–2.28 for non‐steroidal anti‐inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95%confidence interval 2.25–3.82). The self‐controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non‐steroidal anti‐inflammatory drugs (2.71, 95% confidence interval 2.51–2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48–1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95–5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non‐steroidal anti‐inflammatory drugs and was similar when we looked at tricyclic anti‐depressants.

Conclusions:  Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non‐steroidal anti‐inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.
Low‐dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis
Authors: DE SAUSSURE P. , SORAVIA C. , MOREL P. , HADENGUE A.
Published: July 2005

Background:  The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid‐refractory ulcerative colitis are uncertain.

Aim:  To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid‐resistant ulcerative colitis.

Patients and methods:  Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100–200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy.

Results:  Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C‐reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0–8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin.

Conclusions:  Even when dosed for a target C0 of 100–200 ng/mL, oral microemulsion ciclosporin for severe, steroid‐refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.
Long‐term prevention of erosive or ulcerative gastro‐oesophageal reflux disease relapse with rabeprazole 10 or 20 mg vs. placebo: results of a 5‐year study in the United States
Authors: CAOS A. , BREITER J. , PERDOMO C. , BARTH J.
Published: July 2005

Background:  Erosive gastro‐oesophageal reflux disease (GERD) is a chronic condition requiring long‐term maintenance treatment. However, few trials of proton pump inhibitors in maintaining healing of erosive or ulcerative GERD are conducted for longer than 1 year.

Aim:  To compare the efficacy and safety of 10‐ and 20‐mg rabeprazole with placebo in the 5‐year maintenance of healing in patients previously diagnosed with erosive/ulcerative GERD healed in an acute efficacy trial.

Methods:  Patients (N = 497) were randomized to receive once‐daily doses of 10‐ or 20‐mg rabeprazole or placebo. The primary efficacy measure was endoscopically documented absence of oesophageal erosions or ulcerations.

Results:  After 5 years, relapse rates in both rabeprazole groups were significantly lower than with placebo (rabeprazole 20 mg, 11%; 10 mg, 23%; placebo, 63%; P < 0.001 for rabeprazole vs. placebo; P = 0.005 for rabeprazole 20 mg vs. 10 mg). Both rabeprazole doses were significantly superior to placebo in preventing relapse of heartburn frequency and improving patient quality of life. Analyses of adverse events, biopsy findings and laboratory values showed no evidence of clinically significant effects.

Conclusions:  Five‐year maintenance therapy with rabeprazole is effective in preventing relapse of erosive or ulcerative GERD and is well tolerated.
Lower oesophageal sphincter pressure and timed barium oesophagogram: two objective parameters in the non‐invasive assessment of primary achalasia
Authors: MONTAZERI G. , NOURI N. , ESTAKHRI A. , SHIRANI S. , DERAKHSHAN M. H. , YAGHOOBI M. , MIKAELI J. , MALEKZADEH R.
Published: July 2005

Background:  The non‐invasive assessment of primary achalasia is not precise.

Aim:  To compare investigations before and 1 month after balloon dilation in achalasia.

Methods:  Fifty‐two patients with primary achalasia were enrolled. Subjective and objective variables of oesophageal functions were analysed before and 1 month after balloon dilation.

Results:  The mean predilation symptom score, lower oesophageal sphincter pressure, height and volume of barium at 5 min were 7.7 ± 2.6, 62.0 ± 25.1 mmHg, 9.2 ± 6.1 cm and 53.2 ± 49.8 mL respectively; the mean postdilation values were 3.0 ± 3.0, 34.1 ± 12.5 mmHg, 7.9 ± 5.1 cm and 28.0 ± 30.1 mL respectively. The before dilation volume of barium at 5 min correlates significantly with lower oesophageal sphincter pressure (P < 0.01). The mean symptom scores, lower oesophageal sphincter pressure and volume of barium at 5 min dropped significantly after intervention (P < 0.01), but the reduction in barium height at 5 min was not significant. The percentage changes in volume at 5 min significantly predicted the percentage changes in lower oesophageal sphincter pressure (P < 0.01).

Conclusions:  The volume of barium retention at 5 min can predict the lower oesophageal sphincter pressure before and after balloon dilation in primary achalasia. This could be used as a non‐invasive objective tool for initial and post‐dilation assessment.
Philadelphia positive acute lymphoblastic leukaemia of childhood
Authors: Jones Louise K. , Saha Vaskar
Published: July 2005

On current chemotherapeutic regimens, children with Philadelphia positive acute lymphoblastic leukaemia show a heterogeneous response to treatment. A few respond quickly to treatment and achieve long‐term remission. Some fail to achieve remission after induction and the majority respond slowly to treatment. Relapse on treatment is common and remission is sustained in a proportion of cases only after allogeneic stem cell transplantation (allo‐SCT). The use of imatinib along with conventional cytoreductive therapy, prior to allo‐SCT appears to be the most promising strategy. The future lies in the molecular evaluation of response to treatment and combination targeted chemotherapy.
Isolated central nervous system involvement in adult T‐cell lymphoma/leukaemia
Authors: Dungerwalla M. , Osuji N. , Waldman A. D. , Al Jehani F. , Mehta A. , Taylor R. , Wotherspoon A. , Cogill G. , Matutes E.
Published: July 2005

Central nervous system (CNS) presentation of adult T‐cell lymphoma/leukaemia is rare, and almost invariably associated with systemic disease. We report an unusual manifestation of adult T‐cell lymphoma/leukaemia, with isolated CNS involvement and unusual imaging findings. We also describe objective response to antiviral therapy. To our knowledge, this is the first report of such presentation and response.
Gene expression profiling of mantle cell lymphoma cells reveals aberrant expression of genes from the PI3K‐AKT, WNT and TGFβ signalling pathways
Authors: Rizzatti Edgar Gil , Falcão Roberto Passetto , Panepucci Rodrigo Alexandre , Proto‐Siqueira Rodrigo , Anselmo‐Lima Wilma Terezinha , Okamoto Oswaldo Keith , Zago Marco Antonio
Published: July 2005

Microarray studies have revealed the differential expression of several genes in mantle cell lymphoma (MCL), but it is unknown which of these differences are dependent on the transformed MCL cell itself or on the tumour microenvironment. To investigate which genes and signalling pathways are aberrantly expressed in MCL cells we used oligonucleotide microarrays to perform gene expression profiling of both purified leukaemic MCL cells and their normal counterparts, the naive B cells. A total of 106 genes were differentially expressed at least threefold in MCL cells compared with naive B cells; 63 upregulated and 43 downregulated. To validate the microarray results in a larger set of samples, we selected 10 differentially expressed genes and quantified their expression by real‐time polymerase chain reaction in peripheral blood of MCL patients (n = 21), purified MCL cells (n = 6) and naive B cells (n = 4), obtaining fully concordant results. A computer‐assisted approach was used to procure specific molecular signalling pathways that were aberrantly expressed in MCL cells. Several genes related to apoptosis and to the PI3K/AKT, WNT and tumour growth factor β signalling pathways were altered in MCL cells when compared with naive B cells. These pathways may play a significant role in the pathogenesis of MCL and deserve further investigation as candidates for new therapeutic targets.
Viscum album agglutinin‐I induces apoptosis and degradation of cytoskeletal proteins via caspases in human leukaemia eosinophil AML14.3D10 cells: differences with purified human eosinophils
Authors: Lavastre Valérie , Chiasson Sonia , Cavalli Hélène , Girard Denis
Published: July 2005

Although there are several agents that induce neutrophil apoptosis, few are known as inducers of eosinophil apoptosis. As eosinophils are potent effector cells contributing to allergic inflammation and asthma, we investigated whether the pro‐apoptotic agent Viscum album agglutinin‐I (VAA‐I) could induce eosinophil apoptosis. VAA‐I was found to induce apoptosis in eosinophilic AML14.3D10 (3D10) cells and that these cells expressed caspases‐1, ‐2, ‐3, ‐4, ‐7, ‐8, ‐9 and ‐10. VAA‐I‐induced gelsolin degradation was reversed by the pan‐caspase inhibitor N‐benzyloxycarbonyl‐V‐A‐D‐O‐methylfluoromethyl ketone (z‐VAD). Also, paxillin, vimentin and lamin B1 were cleaved by caspases in VAA‐I‐induced 3D10 cells. VAA‐I activated caspase‐3 and ‐8 in 3D10 cells but, unlike z‐VAD, treatment with a caspase‐8 inhibitor slightly reversed apoptosis. Treatment of purified human eosinophils with VAA‐I was found to induce apoptosis, degradation of gelsolin and lamin B1, but unlike 3D10 cells, cleavage of lamin B1 and cell apoptosis was not reversed by z‐VAD. We conclude that VAA‐I is a potent inducer of eosinophil apoptosis and that proteases other than those inhibited by z‐VAD in 3D10 cells are involved in VAA‐I‐induced peripheral blood eosinophil apoptosis and lamin B1 cleavage. Thus, VAA‐I represents a potential candidate for the reduction of the number of eosinophils in diseases where they play important roles.