bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling floodplain sedimentation using particle tracking
Authors: Thonon Ivo , de Jong Kor , van der Perk Marcel , Middelkoop Hans
Published: September 2006

Both climate change and river rehabilitation projects induce changes in floodplain sedimentation. Notably along the lower River Rhine, the sediment deposition patterns and rates are subject to change. To assess the magnitude of these changes, we developed the MoCSED model, a floodplain sedimentation model within a geographical information system for the lower Rhine River. We based MoCSED on the ‘method of characteristics’ (MoC), a particle tracking method that minimizes numerical dispersion. We implemented the MoCSED model in the PCRaster dynamic modelling language. The model input comprises initial suspended sediment concentrations, water levels, flow velocities, and longitudinal and transverse dispersivities. We used a combination of the Krone and Chen concepts to calculate the subsequent sedimentation (SED routine). We compared the model results with sediment trap data for the Bemmel floodplain along the Dutch Waal River during the 2003 inundation. This comparison showed that MoCSED was able to simulate the pattern of sediment deposition. In addition, the model proved to be an improvement in comparison with a conventional raster‐based floodplain sedimentation model for the lower River Rhine. In future, MoCSED may serve well to study the impact of a changing discharge regime due to climate change and floodplain rehabilitation plans on deposition of sediments. Copyright © 2006 John Wiley & Sons, Ltd.
Natural killer cells play a key role in the antitumor immunity generated by chaperone‐rich cell lysate vaccination
Authors: Zeng Yi , Chen Xinchun , Larmonier Nicolas , Larmonier Claire , Li Gang , Sepassi Marjan , Marron Marilyn , Andreansky Samita , Katsanis Emmanuel
Published: September 2006

Tumor derived chaperone‐rich cell lysate (CRCL) when isolated from tumor tissues is a potent vaccine that contains at least 4 of the highly immunogenic heat shock proteins (HSP) such as HSP70, HSP90, glucose related protein 94 and calreticulin. We have previously documented that CRCL provides both a source of tumor antigens and danger signals triggering dendritic cell (DC) activation. Immunization with tumor derived CRCL elicits tumor‐specific T cell responses leading to tumor regression. In the current study, we further dissect the mechanisms by which CRCL simulates the immune system, and demonstrate that natural killer (NK) cells are required for effective antitumor effects to take place. Our results illustrate that CRCL directly stimulates proinflammatory cytokine and chemokine production by NK cells, which may lead to activation and recruitment of macrophages at the tumor site. Thus, this report provides further insight into the function of CRCL as an immunostimulant against cancer. © 2006 Wiley‐Liss, Inc.
Severe pulmonary metastasis in obese and diabetic mice
Authors: Mori Akinori , Sakurai Hiroaki , Choo Min‐Kyung , Obi Ryosuke , Koizumi Keiichi , Yoshida Chiho , Shimada Yutaka , Saiki Ikuo
Published: September 2006

Although obesity is known as a risk factor for several human cancers, the association of obesity with cancer recurrence and metastasis remains to be characterized. Here, B16‐BL6 melanoma and Lewis lung carcinoma cells were intravenously injected into diabetic (db/db) and obese (ob/ob) mice. The number of experimental lung colonies was markedly promoted in these mice when compared with C57BL/6 mice. In contrast, tumor growth at the implanted site was comparable when cells were inoculated orthotopically. The use of B16‐BL6 cells stably transfected with the luciferase gene revealed that the increased metastasis reflected a difference mainly within 6 hr after the intravenous inoculation of tumor cells. Administration of recombinant leptin in ob/ob mice abolished the increase in metastasis early on as well as the decrease in the splenic NK cell number. In addition, depletion of NK cells by an anti‐asialo‐GM1 antibody abrogated the enhanced metastasis in db/db mice. These results demonstrate that metastasis is markedly promoted in diabetic and obese mice mainly because of decreased NK cell function during the early phase of metastasis. © 2006 Wiley‐Liss, Inc.
Increased plasma DNA integrity index in head and neck cancer patients
Authors: Jiang Wei‐Wen , Zahurak Marianna , Goldenberg David , Milman Yelena , Park Hannah Lui , Westra William H. , Koch Wayne , Sidransky David , Califano Joseph
Published: September 2006

Analysis of the length of circulating DNA in plasma has been reported as a marker for solid tumor detection. We assessed the sensitivity and specificity of increased plasma DNA length to identify patients with head and neck squamous cell carcinoma (HNSCC) and monitor posttreatment disease status. Fifty‐eight HNSCC patients with paired pre‐ and postoperative plasma and 47 plasma samples from control subjects were analyzed using quantitative PCR to determine plasma DNA integrity index. We found that the mean DNA integrity index was significantly greater in the plasma from HNSCC patients, 0.24 (95% CI: 0.11, 0.38), when compared to plasma from the control subjects, −2.24 (95% CI: −2.92, −1.56), p < 0.0001 using multivariate analysis. The optimal sensitivity (the value for which sensitivity equals specificity) was found at a plasma DNA integrity index of 0.82: sensitivity, 84.5%; specificity, 83%. However, there was no significant difference noted between pre‐ and postoperative DNA integrity index in plasma samples from HNSCC patients. This study shows that DNA integrity index in the plasma of the patients with HNSCC is increased in comparison with that in the plasma from non‐HNSCC control subjects. Lack of normalization of plasma DNA integrity index after surgical resection implies the persistence of a population of cells with an altered pattern of DNA degradation despite removal of malignancy. © 2006 Wiley‐Liss, Inc.
Food groups and risk of hepatocellular carcinoma: A multicenter case‐control study in Italy
Authors: Talamini Renato , Polesel Jerry , Montella Maurizio , Maso Luigino Dal , Crispo Anna , Tommasi Luigi G. , Izzo Francesco , Crovatto Marina , Vecchia Carlo La , Franceschi Silvia
Published: September 2006

The role of diet, except for alcohol drinking and aflatoxin contamination, in the etiology of hepatocellular carcinoma (HCC) is unclear. A hospital‐based case‐control study was conducted in Italy in 1999–2002, including 185 incident, histologically‐confirmed cases of HCC. Controls were 412 subjects admitted to hospitals for acute, nonneoplastic diseases unrelated to diet. Dietary habits were assessed using a validated food‐frequency questionnaire. Odds ratios (ORs) and the corresponding 95% confidence intervals (CI) were computed using unconditional multiple logistic regression, adjusting for hepatitis B (HBV) and hepatitis C (HCV) virus infection and alcohol drinking. Energy adjustment was carried out by means of the residual model. A significant inverse relation was found between intakes of milk and yoghurt (OR = 0.28; 95% CI: 0.13–0.61), white meats (OR = 0.44; 95% CI: 0.20–0.95), eggs (OR = 0.31; 95% CI: 0.14–0.69), and fruits (OR = 0.48; 95% CI: 0.22–1.05) and HCC risk. The favourable effect of high intakes of milk and yoghurt, white meats, eggs and fruits was consistent across strata of HBV and HCV infections. The present study supports the hypothesis of a role of diet in HCC aetiology. Dietary modifications may be indicated in subjects at high‐risk for HCC. © 2006 Wiley‐Liss, Inc.
Increased risk of gastrointestinal lymphoma in carriers of the 657del5 NBS1 gene mutation
Authors: Steffen Jan , Maneva Galina , Popławska Lidia , Varon Raymonda , Mioduszewska Olga , Sperling Karl
Published: September 2006

The NBS1 gene mutation, 657del5, frequent in the Slavic populations of Central Europe, is found in most patients with Nijmegen breakage syndrome (NBS), a recessive autosomal disorder with a very high incidence of non‐Hodgkin lymphoma (NHL). We have previously described 2 heterozygous 657del5 mutation carriers among 42 adult NHL probands from Central Poland. Here we report 6 additional carriers of the 657del5 mutation and 2 carriers of the pathogenic NBS1 R215W mutation, among 186 other NHL patients also from Central Poland. The 657del5 carrier frequency in the pooled group of these 228 patients was significantly higher than in population controls (OR 5.85, 95% CI: 2.29–15.00, p = 0.0001). Interestingly, 4 of these carriers were found among 37 patients with gastrointestinal lymphoma (OR 19.52, 95% CI: 5.82–65.42, p = 0.0002). These findings imply that heterozygous NBS1 germline mutations may contribute significantly to the overall incidence of NHL, especially of the gastrointestinal tract, in Central Europe. © 2006 Wiley‐Liss, Inc.
Reactive astrogliosis induces astrocytic differentiation of adult neural stem/progenitor cells in vitro
Authors: Faijerson J. , Tinsley R.B. , Apricó K. , Thorsell A. , Nodin C. , Nilsson M. , Blomstrand F. , Eriksson P.S.
Published: September 2006

Neural stem cells reside in defined areas of the adult mammalian brain, including the dentate gyrus of the hippocampus. Rat neural stem/progenitor cells (NSPCs) isolated from this region retain their multipotency in vitro and in vivo after grafting into the adult brain. Recent studies have shown that endogenous or grafted NSPCs are activated after an injury and migrate toward lesioned areas. In these areas, reactive astrocytes are present and secrete numerous molecules and growth factors; however, it is not currently known whether reactive astrocytes can influence the lineage selection of NSPCs. We investigated whether reactive astrocytes could affect the differentiation, proliferation, and survival of adult NSPCs by modelling astrogliosis in vitro, using mechanical lesion of primary astrocytes. Initially, it was found that conditioned medium from lesioned astrocytes induced astrocytic differentiation of NSPCs without affecting neuronal or oligodendrocytic differentiation. In addition, NSPCs in coculture with lesioned astrocytes also displayed increased astrocytic differentiation and some of these NSPC‐derived astrocytes participated in glial scar formation in vitro. When proliferation and survival of NSPCs were analyzed, no differential effects were observed between lesioned and nonlesioned astrocytes. To investigate the molecular mechanisms of the astrocyte‐inducing activity, the expression of two potent inducers of astroglial differentiation, ciliary neurotrophic factor and leukemia inhibitory factor, was analyzed by Western blot and shown to be up‐regulated in conditioned medium from lesioned astrocytes. These results demonstrate that lesioned astrocytes can induce astroglial differentiation of NSPCs and provide a mechanism for astroglial differentiation of these cells following brain injury. © 2006 Wiley‐Liss, Inc.
Effects of stress and corticosterone on activity and plasticity in the amygdala
Authors: Kavushansky Alexandra , Richter‐Levin Gal
Published: September 2006

The basolateral amygdala (BLA) has been repeatedly shown to mediate the effects of stress on memory‐related processes. However, the way in which stress influences BLA itself has not been fully explored. We studied the effects of stress and corticosterone (CORT) on activity and plasticity in the BLA in the rat, using the electrophysiological procedure of long‐term potentiation (LTP) induction in vivo. Rats were exposed to an acute elevated‐platform stress or administered vehicle or 5 mg/kg, 10 mg/kg, or 25 mg/kg of CORT systemically, after which they were anesthetized and prepared for field potential recording in the BLA, in response to stimulation of the entorhinal cortex. The elevated platform stress enhanced baseline responses in BLA and plasma CORT but inhibited amygdalar LTP. Systemic injections of CORT enhanced baseline responses in BLA in a dose‐dependent manner but did not influence amygdalar LTP. Posttetanic potentiation (PTP) was similarly reduced in CORT‐ and vehicle‐injected groups, possibly because of an additional stress from the injection, thus implying that PTP and LTP in the amygdala differentially react to stress. These results suggest that the increase in amygdalar baseline activity following the exposure to stress may be mediated by the concomitant increase in plasma CORT. However, the suppression of amygdalar LTP is not a result of elevated levels of CORT, suggesting that activity and plasticity in the amygdala might be mediated by different mechanisms. © 2006 Wiley‐Liss, Inc.
Hesr1 knockout mice exhibit behavioral alterations through the dopaminergic nervous system
Authors: Fuke Satoshi , Minami Natsumi , Kokubo Hiroki , Yoshikawa Ayumu , Yasumatsu Hiroshi , Sasagawa Noboru , Saga Yumiko , Tsukahara Toshifumi , Ishiura Shoichi
Published: September 2006

The basic helix‐loop‐helix (bHLH) transcriptional factor Hesr1 gene (hairy and enhancer of split‐related 1, also called Hey1/HRT1/CHF2/HERP2) has been identified and characterized as a member of the subfamily of hairy/Enhancer of split, and shown to be involved in cardiovascular and neural development. We report that HESR1 binds directly to a part of the 3′ non‐coding region of the human dopamine transporter (DAT1) gene and represses the endogenous DAT1 gene in HEK293 cells. To investigate functions of the HESR1 gene in the dopaminergic nervous system in vivo, we analyzed the expressions of dopamine‐related genes in the postnatal day 0 whole brains of Hesr1 knockout mice by real‐time RT‐PCR analysis. Several dopamine‐related genes, such as DAT, dopamine receptors D1, D2, D4, and D5, were significantly upregulated. Moreover, young adults of Hesr1 knockout mice showed a decrease in spontaneous locomotor activity and a reduction in exploratory behavior or behavioral responses to novelty in the open‐field, and elevated plus‐maze tests. These results indicate that the HESR1 gene is related to neuropsychiatric disorders and behavioral traits through the dopaminergic nervous system. © 2006 Wiley‐Liss, Inc.
Astrocytes are more resistant than cerebral endothelial cells toward geno‐ and cytotoxicity mediated by short‐term oxidative stress
Authors: Bresgen Nikolaus , Jaksch Heidi , Bauer Hans‐Chr. , Eckl Peter , Krizbai Istvan , Tempfer Herbert
Published: September 2006

Evidence is accumulating that capillary endothelial cells (cEC) and astrocytes play a pivotal role in neuroprotection, in particular with respect to counteract oxidative injury. Furthermore, differences among both cell types in response to oxidative stress have been shown and astrocytes seem to be more tolerant in terms of cytotoxicity, however, no reports exist on oxidative stress mediated genotoxicity in astrocytes. We investigated genotoxic and cytotoxic effects of oxidative stress in astrocytes and cECs induced by hypoxia/reoxygenation or by the redox cycling quinone DMNQ. Additionally, the dependence of these effects on glucose availabilty was also studied. On exposure to Hy/Re or 10 μM DMNQ for 24 hr, the frequency of micronucleated and apoptotic cells was significantly increasing, however, astrocytes proved to be more resistant to apoptosis induction, in particular on use of DMNQ. In astrocytes, the low background rates of necrotic cells were not affected and a significant necrosis induction was only detectable in cECs exposed to DMNQ for 24 hr. Short‐term exposure to DMNQ (1 hr) had no effect in astrocytes but exerted significant geno‐ and cytotoxicity in cECs. Increasing the glucose concentration markedly reduced oxidative stress mediated geno‐ and cytotoxicity in astrocytes. Surprisingly, glucose deprivation (aglycemia) suppressed DMNQ induced micronucleus formation in astrocytes without affecting the frequency of apoptotic cells. Our results indicate that astrocytes are more resistant to oxidative stress than cECs, in particular regarding the potential to counteract genotoxicity as well as apoptosis induction mediated by a short term oxidative insult. © 2006 Wiley‐Liss, Inc.
Lack of neprilysin suffices to generate murine amyloid‐like deposits in the brain and behavioral deficit in vivo
Authors: Madani Rime , Poirier Raphael , Wolfer David P. , Welzl Hans , Groscurth Peter , Lipp Hans‐Peter , Lu Bao , Mouedden Mohammed El , Mercken Marc , Nitsch Roger M. , Mohajeri M. Hasan
Published: September 2006

Accumulation of the β‐amyloid peptide (Aβ) in the brain is a major pathological hallmark of Alzheimer's disease (AD), leading to synaptic dysfunction, neuronal death, and memory impairment. The levels of neprilysin, a major Aβ‐degrading enzyme, are decreased in AD brains and during aging. Because neprilysin cleaves Aβ in vivo, its down‐regulation may contribute to the pathophysiology of AD. The aim of this study was to assess the consequences of neprilysin deficiency on accumulation of murine Aβ in brains and associated pathologies in vivo by investigating neprilysin‐deficient mice on biochemical, morphological, and behavioral levels. Aged neprilysin‐deficient mice expressed physiological amyloid precursor protein (APP) levels and exhibited elevated brain Aβ concentrations and amyloid‐like deposits in addition to signs of neuronal degeneration in their brains. Behaviorally, neprilysin‐deficient mice acquired a significantly weaker conditioned taste aversion that extinguished faster than the aversion of age‐matched controls. Our data establish that, under physiological APP expression levels, neprilysin deficiency is associated with increased Aβ accumulation in the brain and leads to deposition of amyloid‐like structures in vivo as well as with signs of AD‐like pathology and with behavioral deficits. © 2006 Wiley‐Liss, Inc.
Micro‐Raman and IR study of the compressive behaviour of poly(paraphenylene benzobisoxazole) (PBO) fibres in a diamond‐anvil cell
Authors: Colomban Philippe , Aidi‐Mounsi Achraf , Limage Marie‐Hélène
Published: September 2006

The micro/nano structural evolution of PBO (poly(paraphenylenebenzobisoxazole), commercial name Zylon) fibres has been studied by Raman and IR spectroscopy in a diamond‐anvil cell, up to ∼15 GPa. Different modes were considered in the 900–1700 cm−1 (Raman) and 800–3300 cm−1 (IR) spectral range. The material behaviour appears more similar to that of a densely packed inorganic structure than to the behaviour previously observed for polyamide fibres, and is related to the compact arrangement of the rigid heterocyclic rings. Wavenumber shift starts with increase in pressure and a transition between the two regimes was revealed at ∼2–2.5 GPa, and it was assigned to the loss of order between neighbouring PBO chains. A good correlation is observed between the macroscopic mechanical properties and the nanomechanics at the chemical bond scale. Copyright © 2006 John Wiley & Sons, Ltd.
Lanthanidocene Borohydrides: Alternative Precursors for Olefin and Conjugated Diene Polymerization Catalysts
Authors: Thuilliez Julien , Spitz Roger , Boisson Christophe
Published: September 2006

Summary: The neodymium borohydride complexes Me2Si(3‐Me3Si‐C5H3)2NdBH4(THF)2 and [Me2Si(C5H4)(C13H8)Nd(BH4)2][Li(THF)] · 0.5LiBH4 were prepared. These compounds in combination with Mg(Bu)(Oct) were investigated as catalytic systems for polymerization of ethylene and copolymerization of ethylene with butadiene. Similar polymerization results were obtained using these new precursors, in comparison with chloride analogues. This suggests that the same active species are formed in both cases. The easier isolation and characterization of the complex, [Me2Si(C5H4)(C13H8)Nd(BH4)2][Li(THF)] · 0.5LiBH4, than its chloride analogue constitutes the evidence of the interest of the new precursor family.

Preparation of neodymocene borohydrides and their use as precursors for copolymerization of ethylene with butadiene.

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Preparation of neodymocene borohydrides and their use as precursors for copolymerization of ethylene with butadiene.
Synchronized brain network underlying postural tremor in Wilson's disease
Authors: Südmeyer Martin , Pollok Bettina , Hefter Harald , Gross Joachim , Butz Markus , Wojtecki Lars , Timmermann Lars , Schnitzler Alfons
Published: September 2006

Common neurological manifestation of Wilson's disease (WD) is a postural tremor of the upper extremities. Recently, the primary sensorimotor cortex (S1/M1) has been shown to be involved in WD postural tremor generation. However, neuropathological changes in WD are mostly observed in subcortical structures. We therefore aimed to investigate whether S1/M1 may be functionally interconnected with other brain areas. In five WD patients, we used magnetoencephalography and surface electromyography (EMG) to record simultaneously cerebral neuronal activity and muscular activity during sustained posture of the right forearm. As demonstrated previously, the strongest coupling to tremor EMG was observed in the contralateral S1/M1. This area was taken as reference in order to identify and localize cerebro–cerebral coherence at tremor frequency and its first harmonic. The analysis revealed significant coherence within an oscillatory network including S1/M1, higher cortical motor areas (premotor cortex, PM; supplementary motor area, SMA), posterior parietal cortex (PPC) and thalamus contralateral as well as the cerebellum ipsilateral to the tremor forearm. Flow of information was mainly of bidirectional nature. Taken together, our results indicate that WD postural tremor is generated within a synchronized cerebello–thalamo–cortical network, comprising S1/M1, higher cortical motor areas (SMA, PM), and PPC. © 2006 Movement Disorder Society
Nitric oxide, a double edged sword in cancer biology: Searching for therapeutic opportunities
Authors: Mocellin Simone , Bronte Vincenzo , Nitti Donato
Published: September 2006

Nitric oxide (NO) is a pleiotropic molecule critical to a number of physiological and pathological processes. The last decade has witnessed major advances in dissecting NO biology and its role in cancer pathogenesis. However, the complexity of the interactions between different levels of NO and several aspects of tumor development/progression has led to apparently conflicting findings. Furthermore, both anti‐NO and NO‐based anticancer strategies appear effective in several preclinical models. This paradoxical dichotomy is leaving investigators with a double challenge: to determine the net impact of NO on cancer behavior and to define the therapeutic role of NO‐centered anticancer strategies. Only a comprehensive and dynamic view of the cascade of molecular and cellular events underlying tumor biology and affected by NO will allow investigators to exploit the potential antitumor properties of drugs interfering with NO metabolism. Available data suggest that NO should be considered neither a universal target nor a magic bullet, but rather a signal transducer to be modulated according to the molecular makeup of each individual cancer and the interplay with conventional antineoplastic agents. © 2006 Wiley Periodicals, Inc. Med Res Rev, 27, No. 3, 317–352, 2007
Transcription profile in mouse four‐cell, morula, and blastocyst: Genes implicated in compaction and blastocoel formation
Authors: Cui Xiang‐Shun , Li Xing‐Yu , Shen Xing‐Hui , Bae Yong‐Ju , Kang Jason‐Jongho , Kim Nam‐Hyung
Published: September 2006

To gain insight into early embryo development, we utilized microarray technology to compare gene expression profiles in four‐cell (4C), morula (MO), and blastocyst (BL) stage embryos. Differences in spot intensities were normalized, and grouped by using Avadis Prophetic software platform (version 3.3, Strand Genomics Ltd.) and categories were based on the PANTHER and gene ontology (GO) classification system. This technique identified 622 of 7,927 genes as being more highly expressed in MO when compared to 4C (P < 0.05); similarly, we identified 654 of 9,299 genes as being more highly expressed in BL than in MO (P < 0.05). Upregulation of genes for cytoskeletal, cell adhesion, and cell junction proteins were identified in the MO as compared to the 4C stage embryos, this means they could be involved in the cell compaction necessary for the development to the MO. Genes thought to be involved in ion channels, membrane traffic, transfer/carrier proteins, and lipid metabolism were also identified as being expressed at a higher level in the BL stage embryos than in the MO. Real‐time RT‐PCR was performed to confirm differential expression of selected genes. The identification of the genes being expressed in here will provide insight into the complex gene regulatory networks effecting compaction and blastocoel formation. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Generation of viable fish from cryopreserved primordial germ cells
Authors: Kobayashi Terumasa , Takeuchi Yutaka , Takeuchi Toshio , Yoshizaki Goro
Published: September 2006

An increasing number of wild fish species are in danger of extinction, often as a result of human activities. The cryopreservation of gametes and embryos has great potential for maintaining and restoring threatened species. The conservation of both paternal and maternal genetic information is essential. However, although this technique has been successfully applied to the spermatozoa of many fish species, reliable methods are lacking for the long‐term preservation of fish eggs and embryos. Here, we describe a protocol for use with rainbow trout (Oncorhynchus mykiss) primordial germ cells (PGCs) and document the restoration of live fish from gametes derived from these cryopreserved progenitors. Genital ridges (GRs), which are embryonic tissues containing PGCs, were successfully cryopreserved in a medium containing 1.8 M ethylene glycol (EG). The thawed PGCs that were transplanted into the peritoneal cavities of allogenic trout hatchlings differentiated into mature spermatozoa and eggs in the recipient gonads. Furthermore, the fertilization of eggs derived from cryopreserved PGCs by cryopreserved spermatozoa resulted in the development of fertile F1 fish. This PGC cryopreservation technique represents a promising tool in efforts to save threatened fish species. Moreover, this approach has significant potential for maintaining domesticated fish strains carrying commercially valuable traits for aquaculture purposes. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Effects of 138–355, a β3‐adrenoceptor selective agonist, on relaxation of the human detrusor muscle in vitro
Authors: Yamanishi Tomonori , Yasuda Kosaku , Kitahara Satoshi , Nakai Hideo , Yoshida Ken‐Ichiro , Iizuka Hiroyuki
Published: September 2006

Aims

β‐adrenoceptors are the predominant β‐adrenoceptor subtype present in the bladder and urethra. This study investigates the effects of 138–355, an active‐metabolite of TT‐138 and β3‐adrenoceptor agonist, on relaxation of the human detrusor in vitro.

Methods

Tumor‐free tissue samples of human bladder muscle from 39 patients undergoing total cystectomy due to bladder cancer were obtained, and the mucosa and serosa were removed. Tissues were mounted in 5 or 10 ml organ baths containing Krebs solution, which was gassed with 95% O2and 5% CO2. Resting tension of 1 g was obtained. When the contraction had stabilized, increasing concentrations of β adrenoceptor agonists (non‐selective, isoprenaline; β2‐selective, clenbuterol; β3‐selective, 138–355 and BRL37344) and propiverine (a non‐selective anti‐muscarinic antagonist) were added cumulatively and concentration‐relaxation curves (CRCs) were obtained. CRCs to 138–355 were obtained in the absence and presence of SR59230A, a β3‐selective antagonist, and antagonist affinity values (pA2) were calculated from the Schild plot.

Results

Isoproterenol, clenbuterol, 138–355 and BRL37344 concentration‐dependently relaxed isolated human urinary bladder strips with pEC50value being 6.76±0.17, 5.23±0.22, 5.80±0.26 and 5.90±0.28, respectively. Following antagonist assay, it was observed that concentration‐relaxation curves to 138–355 was competitively antagonized by β3‐ adrenoceptor antagonist, SR59230A, with a pA2value of 7.01±0.45 and with a Schild slope of 0.72±0.07.

Conclusions

Involvement of the β3‐adrenoceptor appears to be greater than that of the β3‐adrenoceptor for relaxations of the human bladder. The relaxation response of 138–355 appears to be mediated via the β3‐adrenoceptor stimulation. Neurourol. Urodynam. 25:815–819, 2006. © 2006 Wiley‐Liss, Inc.
The natural history of overactive bladder and stress urinary incontinence in older women in the community: A 3‐year prospective cohort study
Authors: Donaldson M.M.K. , Thompson J.R. , Matthews R.J. , Dallosso H.M. , McGrother C.W.
Published: September 2006

Aims

This is the first study designed to describe the natural history of stress urinary incontinence (SUI) and overactive bladder (OAB), using validated symptom syndrome severity scores developed for the purpose.

Methods

Two separate but related studies were involved, (i) a clinic sample (N = 2,052) from a randomised controlled trial (RCT) and (ii) a prospective cohort study (N = 12,750) with 3‐year follow‐up. Subjects in both studies were women aged 40 or more living in the community, approached using similar postal questionnaires. Severity scores using standardised urinary symptoms were derived for SUI and OAB from weightings obtained from logistic regression models of symptoms in relation to urodynamic diagnosis. Symptom severity scores were plotted for baseline and 3 years of follow‐up to demonstrate the natural history of the main categories of SUI and OAB.

Results

Overactive bladder and SUI syndrome severity scores showed good criterion validity in relation to relevant clinical measures and good test‐retest reliability. OAB severity increased progressively with age including a period of accelerated increase in the 60s. In contrast, SUI severity showed two age‐related peaks around age 60 and again at age 80. SUI severity also showed a more fluctuating pattern from year to year compared to OAB.

Conclusions

Contrasting patterns of natural history for OAB and SUI syndromes were identified consistent with differences in the patterns of related co‐morbidities. Further studies are needed to confirm these findings. Neurourol. Urodynam. 25:709–716, 2006. © 2006 Wiley‐Liss, Inc.
Which questionnaire? A psychometric evaluation of three patient‐based outcome measures used to assess surgery for stress urinary incontinence
Authors: Reid Fiona M. , Smith Anthony R.B. , Dunn Graham
Published: September 2006

Aims

The aim of the study was to further validate three patient‐based outcome measures (PBOM) used to assess the outcome of surgery for stress urinary incontinence and to compare their psychometric properties with a view to determining the most appropriate measure for clinical use.

Methods

The work was embedded within a randomized controlled trial of laparoscopic and open colposuspension. The trial recruited 291 women from six centers. The three instruments compared were Bristol Female Lower Urinary Tract Symptom Questionnaire (BFLUTS), Kings Health Questionnaire (KHQ), and the Symptom Severity Index and Symptom Impact Index (SSI/SII). The International Consultation on Incontinence (ICI) ABC grading system of psychometric propertie's reliability, validity, and responsiveness was used to evaluate the instruments.

Results

From the analysis of the psychometric properties of the three instruments, the SSI/SII appeared to have the best psychometric profile; Grade A, BFLUTS was of grade A, and KHQ was of grade B. SSI/SII had a good degree of internal consistency (Cronbach's alpha 0.74–0.78). BFLUTS and KHQ both had domains in which the internal consistency was <0.7. The SSI domain of the SSI/SII was the only domain to correlate to the 1‐hr pad test. All domains of the SSI/SII were able to distinguish those cured from not cured and it was most responsive to change. Unlike the KHQ, the SSI/SII had no significant ceiling or floor effects.

Conclusions

This study has demonstrated that when instruments are used in different populations their psychometric properties may change. All three instruments analyzed had limitations when used as an outcome measure for surgery for stress urinary incontinence. Neurourol. Urodynam. © 2006 Wiley‐Liss, Inc.
Clinical usefulness of urodynamic assessment for maintenance of bladder function in patients with spinal cord injury
Authors: Nosseir Michael , Hinkel Andreas , Pannek Jürgen
Published: September 2006

Aims

The vast majority of spinal cord lesions cause neurogenic bladder disorders. Detrusor hyperreflexia presents a major risk factor for renal damage in these patients. We evaluated the long‐term results of patients with spinal cord injury treated at our institution.

Methods

Eighty spinal cord injury patients (60 male, 20 female; mean age 29.6 years) with at least one follow‐up visit a year for a minimum of five consecutive years, were included in this retrospective analysis. Follow‐up included urodynamic evaluation, sonography of the upper and lower urinary tract, urine examination, and evaluation of renal function. Treatment modifications were based on the urodynamic findings.

Results

Mean follow‐up was 67.3 months (range 60–103 months). At initial presentation, 51 patients performed intermittent catheterization, 7 had indwelling catheters, 10 utilized reflex voiding, 2 patients presented with a Brindley stimulator, 10 patients used abdominal straining. At the end of our study, no patient had signs of renal damage. To achieve that goal, 8 patients underwent sphincterotomy, 3 received a Brindley stimulator, 3 underwent bladder augmentation, one Kock pouch was performed, and 12 patients were treated with botulinum‐A‐toxin injections in the detrusor. Twenty‐two patients received intravesical anticholinergic therapy. In merely three patients, treatment was not modified during the entire follow‐up.

Conclusions

In the long term, treatment strategy of neurogenic bladder dysfunction in patients with spinal cord injury had to be modified in almost all patients. 18.8% underwent surgery. For protection of the upper urinary tract and maintenance of continence, regular urodynamic follow‐up is warranted. Neurourol. Urodynam. 26:228–233, 2007. © 2006 Wiley‐Liss, Inc.
An interior point Newton‐like method for non‐negative least‐squares problems with degenerate solution
Authors: Bellavia Stefania , Macconi Maria , Morini Benedetta
Published: September 2006

An interior point approach for medium and large non‐negative linear least‐squares problems is proposed. Global and locally quadratic convergence is shown even if a degenerate solution is approached. Viable approaches for implementation are discussed and numerical results are provided. Copyright © 2006 John Wiley & Sons, Ltd.
Pig exploitation in the southern Kanto region, Japan
Authors: Anezaki T.
Published: September 2006

This study investigates changes in past human and animal relationships by focusing on pig (Sus scrofa) remains excavated from archaeological sites in southern Kanto, Japan. Pigs and humans have had a close relationship since prehistoric times and the process of change in this relationship, including possible domestication, is one of the major issues in Japanese zooarchaeology. This study attempts to gain a better understanding of the nature of past interaction between humans and pigs by investigating their relative importance compared with other vertebrate remains, kill‐off patterns, and changes in their size and shape at these sites.

The materials used for this study date from the Earliest to Final Jomon (ca. 10,000–2500 BP), Yayoi (ca. 2500–1700 BP) and Kofun (ca. 1700–1300 BP) periods. The relative proportions of pigs were calculated to show the overall trend of pig exploitation in each site. Age at death was obtained based on the state of tooth eruption. Bucco‐lingual crown measurements were taken on the third and fourth premolars and on each cusp of the first and second molars of the mandible, and the logarithmic ratio technique was then applied to these data.

The age structure of Sus varies between different sites in the Jomon Period, and significant changes were observed in the Yayoi and Kofun Periods. A decrease in the relative proportion of pigs in the faunal assemblages was observed from Jomon to Kofun. Three major differences were observed in the size of pigs. The overall size of pigs significantly increased from Early to Middle Jomon, whilst a decrease in size occurred in the Yayoi Period. Finally, overall size increased significantly during the Kofun Period. Together with the archaeological evidence—such as the ritual burial of pigs accompanying human burial—we suggest that the interaction between pigs and humans became gradually stronger at some sites during the Late Jomon Period, and the relationship intensified in the Yayoi Period. Copyright © 2006 John Wiley & Sons, Ltd.
Childhood trauma in several populations from the Iberian Peninsula
Authors: Jiménez‐Brobeil S. A. , Al Oumaoui I. , du Souich Ph.
Published: September 2006

A study was conducted on a collection of 123 juvenile skeletons from various sites dating to the Bronze Age (Argar culture) and from the medieval cemeteries of La Torrecilla, Villanueva de Soportilla and San Baudelio, all in the Iberian Peninsula. No cranial trauma was observed. However, four postcranial fractures were found, including three from Castellón Alto, a typical Argaric village of some urban complexity built on steep terraces in high and rugged terrain. The combination of a hazardous environment and a climate that encourages outdoor play may explain the relatively high frequency of childhood trauma in the burials from the Argar culture. Copyright © 2006 John Wiley & Sons, Ltd.
Earliest evidence of spinal tuberculosis from the Aneolithic Yayoi period in Japan
Authors: Suzuki T. , Inoue T.
Published: September 2006

Tuberculosis has existed from early prehistoric days to modern times. The main causative agents of tuberculosis worldwide are Mycobacterium tuberculosis (M. tuberculosis) and M. bovis, along with M. africanum, M. cenettii and M. microti; these species make up the ‘M. tuberculosis complex’. This worldwide infection has been of special interest to palaeopathologists due to its characteristic bone lesions as well as its great antiquity. Historically, tuberculosis has been recognised in Japan for more than a thousand years. However, the origin and early prevalence of tuberculosis remain unknown. In the present study, we present the earliest evidence of skeletal tuberculosis found in the Aneolithic Yayoi period in Japan (ca. 300 BC to AD 300). The skeletal remains showing typical pathological changes of spinal tuberculosis were dated to between 454 BC and AD 124 by dendrochronological methods using coburied arrow‐shield board and house columns made of Japanese cedar. We discuss the early prevalence of this infectious disease and its influence on the population history of the Japanese from prehistoric to Aneolithic times. Copyright © 2006 John Wiley & Sons, Ltd.
Controlled technology for forming a nanostructured polymer coating for solid pharmaceuticals
Authors: Csontos István , Rónaszegi Krisztián , Szabó András , Keszei Sándor , Anna Péter , Fekete Pál , Marosi György , Nagy Tibor
Published: September 2006

Simple method is proposed for in situ formation of nanodispersion through computer‐controlled emulsion polymerization. The method is based on the application of cationic emulsifier during polymerization, which performs cation exchange with the surface Na ions of montmorillonite nanoparticles. The endpoint of polymerization is detected by Raman microscopy while the structure is determined by atomic force microscopy. The nanodispersion is used in the tablet‐coating process. Raman microscopy provides a new non‐destructive way for controlling the thickness and uniformity of the coatings during the procedure, while the surface defects can be determined by atomic force microscopy. © 2006 John Wiley & Sons, Ltd.
The PedsQL™ brain tumor module: Initial reliability and validity
Authors: Palmer Stephanie N. , Meeske Kathleen A. , Katz Ernest R. , Burwinkle Tasha M. , Varni James W.
Published: September 2006

Background

Brain tumors (BT) are second only to acute lymphoblastic leukemia as the most prevalent form of pediatric cancer, with BT 5‐year survival rates approaching 70%. With increased survival, quality of life has emerged as an essential health outcome. This investigation examines the internal consistency reliability and construct validity of the Pediatric Quality of Life Inventory™ (PedsQL™) Brain Tumor Module.

Methods

The PedsQL™ 4.0 Generic Core Scales, PedsQL™ Multidimensional Fatigue Scale, and PedsQL™ Brain Tumor Module were administered to 99 families. The average age of the 56 boys and 43 girls was 9.76 years (range = 2–18 years). The sample included children with tumors located in the posterior fossa/brainstem (N = 62, 62.6%), supratentorial (N = 15, 15.2%), and midline (N = 22, 22.2%). Children were on treatment (N = 46, 46.5%), off treatment <12 months (N = 19, 19.2%), or off treatment >12 months/long‐term survivor (N = 34, 34.3%). Treatment included radiation (N = 61, 61.6%), surgery (N = 83, 83.8%), chemotherapy (N = 87, 87.9%), and bone marrow transplant (N = 5, 5.1%).

Results

Internal consistency reliability was demonstrated for the 24‐item PedsQL™ Brain Tumor Module (average α = 0.78–0.92, parent proxy‐report, n = 99; average α = 0.76–0.87, child self‐report, n = 51). Construct validity for the PedsQL™ Brain Tumor Module was supported through an analysis of the intercorrelations with the Generic Core Scales and Fatigue Scale.

Conclusions

The findings provide support for the measurement properties of the PedsQL™ Brain Tumor Module. Pediatr Blood Cancer 2007;49:287–293. © 2006 Wiley‐Liss, Inc.
Thromboembolism in children with sarcoma
Authors: Athale Uma , Cox Stephanie , Siciliano Sabrina , Chan Anthony K.C.
Published: September 2006

Background

Thromboembolism (TE) is a common complication and cause of death in adults with cancer. Cancer has been identified as a major risk factor in children with TE. However, the information regarding the epidemiology of TE in children with cancer, especially in association with childhood solid tumors, is scant.

Objective

To define the prevalence and epidemiology of TE in children with sarcoma.

Procedure

Hospital records of children ≤18 years of age with sarcoma diagnosed and treated at McMaster Children's Hospital during January 1990 to December 2005 were reviewed for demographic details, details of diagnosis and therapy for sarcoma, and details of diagnosis and management of TE. Statistical analysis was performed using Fisher's exact t‐test.

Results

Ten of 70 (14.3%; 95% CI; 7.1, 24.7) patients with sarcoma developed symptomatic TE. Patients with CVL‐dysfunction (n = 9) were at significantly higher risk for symptomatic TE compared to those without CVL dysfunction (n = 61) (55.5 vs. 8.2%; P = 0.002, 95% CI; 14.2, 80.5). Patients with pulmonary disease (n = 23) had higher prevalence of TE compared to those without pulmonary disease (n = 47) (26 vs.8.5%; P = 0.07, 95% CI; −2.06, 37.2). Older patients, patients with metastatic disease and those with Ewing sarcoma had higher prevalence of TE.

Conclusions

TE is a significant complication in children with sarcoma. Over 50% of patients with CVL dysfunction had symptomatic TE; such patients may warrant careful evaluation for associated TE. Large prospective studies are needed to define the epidemiology and identify risk factors predisposing to TE in children with sarcoma. Pediatr Blood Cancer 2007;49:171–176. © 2006 Wiley‐Liss, Inc.
Polymorphous hemangioendothelioma in a child with acquired immunodeficiency syndrome (AIDS)
Authors: Paul Stephan R. , Hurford Matthew T. , Miettinen Markku M. , Aronoff Stephen C. , Delvecchio Michael , Grewal Harsh , Tuluc Madalina
Published: September 2006

Polymorphous hemangioendotheliomas (PH) are rare and borderline malignant tumors that are among the wide range of vascular tumors. We report here a 13‐year‐old male presenting with a history of weight loss, opportunistic infections, and lymphadenopathy. He was determined to be HIV positive and to have acquired immunodeficiency syndrome (AIDS). A biopsy of a femoral node was diagnostic of PH. His systemic lymphadenopathy appeared to resolve with anti‐retroviral therapy. This tumor should be considered within the differential diagnoses of pediatric and immunocompromised patients. Pediatr Blood Cancer 2008;50:663–665. © 2006 Wiley‐Liss, Inc.
Impact of proximity to comprehensive sickle cell center on utilization of healthcare services among children with sickle cell disease
Authors: Shankar Sadhna M. , Arbogast Patrick G. , Mitchel Ed , Ding Hua , Wang Winfred C. , Griffin Marie R.
Published: September 2006

Background

The impact of comprehensive care on utilization of healthcare services by children with sickle cell disease (SCD) has not been fully evaluated. We compared the medical care utilization and mortality in children less than 20 years of age with SCD in four regions in the state of Tennessee with and without a comprehensive sickle cell center (CSCC).

Methods

Rates of hospitalizations, outpatient and emergency department (ED) visits, and deaths were measured in a cohort of children aged <20 years with SCD, enrolled in TennCare, from January 1995 to December 2002. TennCare data linked to Tennessee vital records were used to define the population and identify the outcomes. The patients were classified into one of four regions based on their residential address on the day of their hospitalization or outpatient visit.

Results

The cohort consisted of 1,214 children with 6,393 person‐years of follow‐up. Fifty‐six percent of patients resided in the region with the CSCC. This region had the highest overall rates of hospitalization for all children (P < 0.001), while ED and outpatient visits were higher in other areas. The death rates ranged from 1.8 to 4.3 per 1,000 person‐years in the four regions and did not represent statistically significant differences.

Conclusion

No clear pattern of improved utilization of medical care services were identified in relation to proximity of residence to a CSCC. This cohort was not large enough to detect small differences in death rates. In addition, other outcomes that incorporate quality of life measures may be more sensitive to differences in medical care. Pediatr Blood Cancer 2008;50:66–71. © 2006 Wiley‐Liss, Inc.
The pitfalls of proteomics experiments without the correct use of bioinformatics tools
Authors: Biron David G. , Brun Christine , Lefevre Thierry , Lebarbenchon Camille , Loxdale Hugh D. , Chevenet François , Brizard Jean‐Paul , Thomas Frédéric
Published: September 2006

The elucidation of the entire genomic sequence of various organisms, from viruses to complex metazoans, most recently man, is undoubtedly the greatest triumph of molecular biology since the discovery of the DNA double helix. Over the past two decades, the focus of molecular biology has gradually moved from genomes to proteomes, the intention being to discover the functions of the genes themselves. The postgenomic era stimulated the development of new techniques (e.g. 2‐DE and MS) and bioinformatics tools to identify the functions, reactions, interactions and location of the gene products in tissues and/or cells of living organisms. Both 2‐DE and MS have been very successfully employed to identify proteins involved in biological phenomena (e.g. immunity, cancer, host–parasite interactions, etc.), although recently, several papers have emphasised the pitfalls of 2‐DE experiments, especially in relation to experimental design, poor statistical treatment and the high rate of ‘false positive’ results with regard to protein identification. In the light of these perceived problems, we review the advantages and misuses of bioinformatics tools – from realisation of 2‐DE gels to the identification of candidate protein spots – and suggest some useful avenues to improve the quality of 2‐DE experiments. In addition, we present key steps which, in our view, need to be to taken into consideration during such analyses. Lastly, we present novel biological entities named ‘interactomes', and the bioinformatics tools developed to analyse the large protein–protein interaction networks they form, along with several new perspectives of the field.