bluuebunny/crossref_metadata_2025 huggingface dataset:
Release of ibuprofen from poly(ε‐caprolactone‐co‐D,L‐lactide) and simulation of the release
Authors: Ahola Niina , Rich Jaana , Karjalainen Teija , Seppälä Jukka
Published: February 2003

A study was made of the effects of the initial ibuprofen load and of the specimen shape on the release of ibuprofen from poly(ε‐caprolactone‐co‐D,L‐lactide). The mol ratio of the comonomers in the copolymer was 96/4 (caprolactone to lactide) and the experiments were conducted at 37°C in vitro. The results showed that release of ibuprofen is fast and that the rate and profile of the release vary with both the initial load of ibuprofen and the shape of the specimen. The rate of ibuprofen release increases with the initial load and with the surface area‐to‐volume ratio of the specimen, obeying Fickian diffusion. The experimental findings were compared with the results of a mathematical simulation model based on the finite‐difference method. Diffusion parameters needed for the simulation were determined from a separately conducted set of experiments using various methods. For the most part, the results of the simulations and the experiments were in good agreement. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1279–1288, 2003
Lesion progression with time and the effect of vascular occlusion following radiofrequency ablation of the liver
Authors: Wiersinga W J , Jansen M C , Straatsburg I H , Davids P H , Klaase J M , Gouma D J , van Gulik T M
Published: February 2003

Background

The effectiveness of radiofrequency ablation (RFA) under selective vascular occlusion and its effects on architecture and viability of normal liver parenchyma was studied in a porcine model.

Methods

RFA was applied in the liver under general anaesthesia in 18 pigs. Six animals were killed immediately after the procedure and 12 at 24 h. RFA was performed sequentially under four conditions: (1) without vascular occlusion, (2) during occlusion of the hepatic artery, (3) during occlusion of the portal vein and (4) during occlusion of the hepatic artery and portal vein. Liver biopsies from the treated area were stained for conventional histological examination, reduced nicotinamide adenine dinucleotide diaphorase and 5′-nucleotidase activity.

Results

Vascular occlusion significantly increased the size of the coagulation centre after RFA. Combined portal venous and arterial occlusion had no additional effect on lesion size compared with venous or arterial occlusion alone. After 24 h, deterioration of viability was observed in the parenchyma up to 3 cm from the coagulated area.

Conclusion

The efficacy of RFA in liver increases with occlusion of the portal vein or hepatic artery. The extent of secondary heat-induced necrosis in liver parenchyma should be considered for determination of the final size of the ablated area.
Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours
Authors: Langer C , Gunawan B , Schüler P , Huber W , Füzesi L , Becker H
Published: February 2003

Background

The purpose of this study was to review surgical experience with gastrointestinal stromal tumours (GISTs) at a single tertiary university hospital, and to identify morphological and genetic prognostic markers of tumour progression.

Methods

Forty-eight GISTs from 39 patients were reviewed retrospectively. The prognostic significance of DNA copy number changes, measured by comparative genomic hybridization (CGH), and morphological markers in low-risk and high-risk tumours were investigated.

Results

Significantly more patients died from disease after incomplete tumour resection than after complete primary resection (P = 0·020). Tumour size of 5 cm or greater, mitotic count of 2 or more, and proliferative activity greater than 10 per cent were significantly associated with a shorter recurrence-free survival (P = 0·020, P = 0·001 and P = 0·002 respectively). Patients with low-risk tumours had a significantly better outcome than those with high-risk GISTs, both in terms of overall and recurrence-free survival (P ≤ 0·001). CGH performed on 16 tumours revealed fewer DNA sequence copy number changes in low-risk than in high-risk GISTs. Non-progressive GISTs contained significantly fewer genetic alterations than recurrent or metastatic tumours (P < 0·001). Only tumours with more than five changes showed disease progression.

Conclusion

Complete surgical resection is the most important means of cure for GISTs. DNA copy number changes are related to the behaviour of these tumours and may serve as additional prognostic markers.
Effect of a closure device on complication rates in high‐local‐risk patients: Results of a randomized multicenter trial
Authors: Chevalier Bernard , Lancelin Bernard , Koning Rene , Henry Michel , Gommeaux Antoine , Pilliere Remy , Elbaz Meyer , Lefevre Thierry , Boughalem Kamel , Marco Jean , Dupouy Patrick
Published: February 2003

Clinical trials have shown that coronary stenting is associated with a high level of complications at the access site. Arterial sealing devices have proven their efficacy in obtaining immediate hemostasis after sheath removal, in allowing early ambulation, and in improving patient comfort. However, there is no report showing a reduction of local complications related to their use. The purpose of this multicenter study was to compare randomly the efficacy of Angio‐Seal versus compression methods of hemostasis in reducing the rate of access site complications after coronary angioplasty in 612 selected patients with higher risk of local events satisfying at least one of the following high‐risk criteria: age > 70, previous puncture at the same site, history of hypertension, treatment with ticlopidine at least 2 days before the procedure, use of abciximab, 8 Fr access, prolonged heparin treatment after the angioplasty, and use of lytics if fibrinogen > 1 g/l. Group A (n = 306) had immediate sheath removal, Angio‐Seal implantation, and cessation of bed rest 4 hr after the intervention. Group B (n = 306) had sheath removal according to local practice and cessation of bed rest 6–18 hr after the hemostasis procedure, also according to local practice. Clinical follow‐up was done at 1 hr, 4 hr, 24 hr, discharge, and 7 days and a systematic color flow duplex sonography was performed to confirm diagnosis of access site complication. In group A, device deployment and immediate hemostasis were obtained in, respectively, 96.8% and 87% of patients. Time to hemostasis was shorter in group A: 5 vs. 52 min (P < 0.001). Cessation of bed rest was dramatically reduced in group A (438 ± 450 min) vs. group B (952 ± 308 min; P < 0.001). The cumulative rate of complications, using a composite primary endpoint, at 7 days was significantly different between the two groups: 5.9% of group A patients and 18% of group B patients (P < 0.001). This difference was mainly due to the dramatic reduction of prolonged bleeding in group A patients. Angio‐Seal device use in high‐local‐risk patients allows immediate sheath removal and hemostasis with a reduction of local event rate despite a higher level of anticoagulation, compared to regular compression techniques, directly related to a dramatic decrease of prolonged bleeding. Cathet Cardiovasc Intervent 2003;58:285–291. © 2003 Wiley‐Liss, Inc.
Percutaneous suture‐mediated closure of femoral access sites deployed through the procedure sheath: Initial clinical experience with a novel vascular closure device
Authors: Eggebrecht Holger , Naber Christoph , Woertgen Uta , Ringe Sonia , Konorza Thomas F.M. , Schmermund Axel , von Birgelen Clemens , Haude Michael , Kroeger Knut , Erbel Raimund , Baumgart Dietrich
Published: February 2003

The objective of this study was to assess the initial safety and feasibility of a novel suture‐mediated device for closure of femoral access sites immediately after diagnostic or interventional cardiac catheterization. In a prospective study, 150 patients (mean age, 61.5 years; 109 male) underwent femoral access closure with a novel suture closure device (Superstitch, Sutura) immediately after diagnostic (n = 106) or interventional (n = 44) catheterization procedures, independently of the coagulation status. All patients were monitored for 24 hr after the procedure. The closure device was successfully deployed in 92% of patients. Immediate hemostasis was achieved in 77% of patients with no differences between patients undergoing diagnostic catheterization or coronary interventions (79% vs. 73%; P = 0.659). After 2 min of additional light manual compression, hemostasis was achieved in 92% of patients. There was one major complication requiring vascular surgery (0.7%). The novel suture closure device is a safe and effective device that allows for immediate closure of femoral puncture sites after both diagnostic and interventional procedures with a low rate of major complications. Cathet Cardiovasc Intervent 2003;58:313‐321. © 2003 Wiley‐Liss, Inc.
A review of p53 expression and mutation in human benign, low malignant potential, and invasive epithelial ovarian tumors
Authors: Kmet Leanne M. , Cook Linda S. , Magliocco Anthony M.
Published: February 2003

BACKGROUND

In the current study, the authors present pooled data from studies that investigated p53 protein expression and/or mutation in human epithelial ovarian tumors.

METHODS

The English literature in the MEDLINE, PubMed, and Ingenta databases was searched to the end of the year 2000 to identify relevant studies. Data were pooled across eligible studies, and the prevalence of p53 expression and mutation among benign, low malignant potential (LMP), and invasive tumors was determined. Prevalence estimates by tumor histology, International Federation of Gynecology and Obstetrics (FIGO) stage, and grade also were calculated.

RESULTS

The pooled prevalence estimate for p53 overexpression among epithelial ovarian carcinomas was 51% (95% confidence intervals [95% CI], 50–53%) compared with 17% (95% CI, 15–20%) among LMP tumors and 7% (95% CI, 5–10%) among benign tumors. p53 mutation prevalence estimates were 45% (95% CI, 42–47%), 5% (95% CI, 2–9%), and 1% (95% CI, 0–5%), respectively, for invasive, LMP, and benign tumors. The prevalence of these p53 abnormalities was found to be associated positively with increasing tumor grade and stage. Differences based on histologic subtype also were found.

CONCLUSIONS

Although these pooled estimates might appear to offer support for various hypotheses regarding the role of p53 in ovarian carcinoma, the limitations inherent in these data hamper the interpretation of the significance of any of the findings. Future studies will require innovative methods to address the limitations of many previous investigations and more comprehensive investigation into defective tumor suppression mechanisms. Cancer 2003;97:389–404. © 2003 American Cancer Society.

DOI 10.1002/cncr.11064
EMAS and its local diffusion in Italy
Authors: Jirillo Rita , Rocchi Andrea , Martucci Olimpia
Published: February 2003

Due to the growing awareness among enterprises of the relevance of ‘sustainable development’, applications of the Environmental Management and Audit Scheme (EMAS) in Italy are expanding. With the second era of EMAS (EMAS II), this scheme will become a global instrument, enabling Italian small and medium enterprises (SMEs) to master environmental challenges while improving their competitive position. This report intends to demonstrate that area and local agreements between local government units and research centres, such as universities or energy and environmental boards, can simplify and improve the diffusion of EMAS in the country. Reported examples of some small Italian municipalities that have applied EMAS are demonstrations of how government units can increase all citizens' quality of life while taking care of environmental aspects. Since 1993, the year of the first applications of Regulation 1836/93, local government units have understood the important role they can play in this subject.

This work illustrates that the development of ISO and EMAS local applications must be based on government's local promotion aimed at encouraging enterprises to voluntarily adopt these instruments for environmental safeguard. Copyright © 2003 John Wiley & Sons, Ltd. and ERP Environment.
The changing world demography of type 2 diabetes
Authors: Green Anders , Christian Hirsch Niels , Krøger Pramming Stig
Published: February 2003

In recent years it has been estimated that the current global prevalence of type 2 diabetes amounts to about 150 million patients. Projections suggest that by the year 2025 the number of prevalent patients in the world will reach approximately 300 million. It is assumed that the increase in the number of patients will be most pronounced in nations currently undergoing socio‐economic development including increasing urbanization. The technique used to provide these estimates is based on results from available, contemporary survey results, combined with expected future trends in demographic indicators. We suggest that the currently available methods for the estimation of the future global burden of type 2 diabetes mellitus yield underestimates. Further modifications and validity tests of the modelling techniques are necessary in order to develop a reliable instrument to globally monitor the effects of the struggle against the diabetes problem. Copyright © 2002 John Wiley & Sons, Ltd.
A study of the buying price of photovoltaic electricity under a carbon tax regime
Authors: Kemmoku Yoshishige , Shundoh Goh , Takikawa Hirofumi , Kawamoto Teru , Sakakibara Tateki
Published: February 2003

Assuming that photovoltaic (PV) systems are adopted in residential houses under a carbon tax regime, the economic performance of PV systems is investigated from the standpoint of an electric utility. The economic performance is estimated by using the buying price of PV electricity and the PV economic index, which is defined as the ratio of the buying price to the generation cost of the electric utility. Because these values depend on electric power development and operation, the best mix and the operation of power plants are obtained by linear programming subject to restrictions on power generation. Then, the buying price of PV electricity is calculated from the total cost of the electric utility. The buying price means the upper limit at which the electric utility never suffers a loss. The buying price is also compared with the power generation cost. The parameters are the prevalence attainment ratio of PV systems (0 to 100%), the upper limit of newly developed nuclear power plants (0 to 4 GW/10 y), and the generated energy ratio of coal‐fired thermal plants (0 to 15%). Chubu Electric Power Company, Inc. is used as the electric utility. The calculation results show that the buying price of PV electricity increases linearly with increasing carbon tax rate, and its values are 9 and 11.5 yen/kWh when the carbon tax rate is 0 and 25 thousand yen/t‐C, respectively, which does not depend on the prevalence attainment ratio of PV systems and the upper limit of newly developed nuclear power plants. It is not the carbon tax rate but the newly developed nuclear power plant that influences the PV economic index. The values of the PV economic index are 1.35 to 1.45 and 1.50 to 1.60 when the newly developed nuclear power plant capacity is 0 and 4 GW/10 y, respectively. These results show that the economic performance of PV systems is increased by developing nuclear power plants at a certain rate and introducing a carbon tax. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(2): 38–49, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10067
A study of a micro co‐generation system's conformation for residential use considering observed fluctuating characteristics of hot‐water demand
Authors: Kato Takeyoshi , Iida Tetsuhisa , Wu Kai , Suzuoki Yasuo
Published: February 2003

This paper discusses a conformation of a micro co‐generation system (µCGS) for residential use. The evaluation is based on the hot‐water demand observed in three families who live in the same apartment house. Assuming DSS operation of µCGS, we evaluated the required capacity of PEFC, hot‐water tank, and backup boiler to meet a series of daily hot‐water demand observed in three houses. The results are: (1) µCGS with 2‐kW PEFC and 350‐L hot‐water tank are required in family B when µCGS is not equipped with the backup boiler, (2) the additional 5 kW of the backup boiler reduces the required capacity of the hot‐water tank by 50 L, (3) the evaluation based on hourly averaged hot‐water demand patterns would underestimate the required capacity of the hot‐water tank, (4) the required capacity of the hot‐water tank could be reduced by the leveling effect of the hot‐water demand pattern along three families. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(2): 30–37, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10080
Calculation method for strand current distributions in armature winding of a turbine generator
Authors: Takahashi Kazuhiko , Takahashi Miyoshi , Sato Masaki
Published: February 2003

We have developed a calculation method for the strand current distributions in the turbine generator armature windings. These distributions are calculated by using a circuit equation and a 3D finite element method. In the circuit equation, the strand current is solved by introducing a circulating current at each strand of the armature windings. The induced voltage in the circuit equation is produced by leakage flux of the coil end region. The leakage flux is obtained by the 3D finite element method. The calculated strand current distributions had good agreement with the measurements of 360°, 450°, and 540° transposed model coils. © 2003 Wiley Periodicals, Inc. Electr Eng Jpn, 143(2): 50–58, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.10131
Analytical platforms to assess the authenticity of cocoa butter
Authors: Ulberth Franz , Buchgraber Manuela
Published: February 2003

This paper reviews strategies to detect and analyse cocoa butter equivalents added to genuine cocoa butter or to chocolate products. The legal background of the issue is that current European legislation allows the addition of vegetable fats other than cocoa butter to chocolate up to a level of 5% of the product weight, provided that the addition is correctly indicated on the label. However, the Directive fails to specify a method of analysis to enforce compliance.

The principal themes highlight compositional data (triglyceride and fatty acid composition, components of the unsaponifiable matter) of cocoa butter from different origins and suitable raw materials used for the formulation of cocoa butter equivalents, and explains how analytical techniques (gas‐liquid chromatography, high‐performance liquid chromatography, infrared spectroscopy, pyrolysis mass spectrometry) make use of subtle differences between the two commodities to detect commingling.
AMPA/kainate receptors in mouse spinal cord cell‐specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier
Authors: Brand‐Schieber Elimor , Werner Peter
Published: February 2003

Spinal cord white matter is susceptible to AMPA/kainate (KA)‐type glutamate receptor‐mediated excitotoxicity. To understand this vulnerability, it is important to characterize the distribution of AMPA/KA receptor subunits in this tissue. Using immunohistochemistry and laser confocal microscopy, we studied the expression sites of AMPA/KA receptor subunits in mouse spinal cord. The white matter showed consistent immunoreactivity for AMPA receptor subunit GluR2/3 and KA receptor subunits GluR6/7 and KA2. In contrast, antibodies against GluR1, GluR2, GluR4 (AMPA), and GluR5 (KA) subunits showed only weak and occasional labeling of white matter. However, gray matter neurons did express GluR1 and GluR2, as well as GluR2/3. The white matter astrocytes were GluR2/3 and GluR6/7 immunopositive, while the gray matter astrocytes displayed primarily GluR6/7. Both exclusively and abundantly, KA2 labeled oligodendrocytes and myelin, identified by CNPase expression. Interestingly, myelin basic protein, another myelin marker, showed less correlation with KA2 expression, placing KA2 at specific CNPase‐containing subdomains. Focal points of dense KA2 labeling showed colocalization with limited, but distinct, axonal regions. These regions were identified as nodes of Ranvier by coexpressing the nodal marker, ankyrin G. Overall, axonal tracts showed little, if any, AMPA/KA receptor expression. The proximity of oligodendrocytic KA2 to the axonal node and the paucity of axonal AMPA/kainate receptor expression suggest that excitotoxic axonal damage may be secondary and, possibly, mediated by oligodendrocytes. Our data demonstrate differential expression of glutamate AMPA and KA receptor subunits in mouse spinal cord white matter and point to astrocytes and oligodendrocytes as potential targets for pharmacological intervention in white matter glutamate excitotoxicity. GLIA 42:12–24, 2003. © 2003 Wiley‐Liss, Inc.
Functional characterization of mannose receptor expressed by immunocompetent mouse microglia
Authors: Zimmer Heiko , Riese Sigrid , Régnier‐Vigouroux Anne
Published: February 2003

The mannose receptor is a pattern‐recognition receptor involved in innate and adaptive immunity. The receptor is mainly expressed by macrophages and, within the brain, by astrocytes and microglia. This study reports for the first time the effects of two classical proinflammatory (interferon‐γ, IFNγ) and anti‐inflammatory (interleukin‐4, IL‐4) cytokines on the levels of expression and activity of the mannose receptor expressed by mouse microglia, the brain resident macrophages. As observed for macrophages, IFNγ treatment led to a decrease and IL‐4 to an increase of mannose receptor expression. Consequently, the rates of pinocytosis were strongly upregulated by IL‐4 and inhibited by IFNγ. This latter, however, resumed with time and reached again the constitutive rate of pinocytosis. This recovery resulted from an increased pinocytic activity of the few mannose receptor molecules still expressed by IFNγ‐treated microglia. This may suggest a brain‐specific regulation of the effects of IFNγ since such a phenomenon has not been observed in macrophages. Together, these observations demonstrate that cytokine‐stimulated immunocompetent microglia express a functional mannose receptor. GLIA 41:89–100, 2003. © 2003 Wiley‐Liss, Inc.
Protective effect of glial cells against lipopolysaccharide‐mediated blood‐brain barrier injury
Authors: Descamps Laurence , Coisne Caroline , Dehouck Bénédicte , Cecchelli Romeo , Torpier Gérard
Published: February 2003

Numerous infections of the central nervous system are characterized by altered blood‐brain barrier (BBB) functions leading to brain damage. To study the mechanisms that cause BBB disruption in these pathologies, we used an in vitro BBB model consisting of a coculture of brain capillary endothelial cells and glial cells. When these endothelial cells were submitted alone to lipopolysaccharide (LPS), added in the luminal compartment, a huge increase in the paracellular permeability of the monolayer was observed. As glial cells surrounding the brain capillaries are of prime importance in specifying at least some cellular properties, we investigated whether glial cells would be able to modulate this endothelial cell response to LPS. When endothelial cells were incubated with LPS added luminally, in the presence of glial cells, LPS surprisingly had no effect on the endothelial cell monolayer permeability, suggesting a protective effect of glial cells on the LPS‐mediated injury. As in our experiments, the endotoxin does not interact with the glial cell population. This protective effect suggests a close communication between cerebral endothelial cells and brain parenchymal cells. In our coculture model, the glial cell population is a mixture of astrocytes, oligodendrocytes, and microglial cells. Further experiments performed with purified astrocytes showed that microglial cells or oligodendrocytes, or both, are essential for the complete protection of the endothelial cell monolayer integrity. All these results are direct evidence for a modulatory effect of glial cells on brain capillary endothelial cell response in the pathogenesis of endotoxemia. GLIA 42:46–58, 2003. © 2003 Wiley‐Liss, Inc.
Perceived social support from supervisor and group members' psychological and situational characteristics as predictors of subordinate performance in Thai work units
Authors: Bhanthumnavin Duchduen
Published: February 2003

The main purpose of this study was to examine the relationship between three dimensions of perceived social
support from supervisor (PSSS) (emotional, informational, and material) and subordinate
performance (self‐report and supervisory rating). The second purpose was to study the effects of
psychological and situational factors on subordinate performance.

Usable data of 355 matched supervisor‐subordinate pairs working in health centers in Thailand were
analyzed. Results revealed that female subordinates receiving all three types of support received higher performance
ratings from their supervisors than did their male counterparts. Perceived organizational support,
self‐efficacy, and location of workplace were also associated with subordinate performance. Discussion,
recommendations for future research, implications for HRD in Thailand, and limitations are presented.
Biological and caregiver correlates of behavioral inhibition
Authors: Partridge Ty
Published: February 2003

The aim of this study was to explore the relationships among measures of behavioral inhibition, physiological reactivity, and caregiver attitudes. Measures comprised of heart rate; survey assessments of caregiver empathy with the child, appropriateness of caregiver developmental expectations of the child, and use of positive discipline techniques; and observational measures of behavioral inhibition were gathered in a laboratory setting on 72, 5–6‐year old children. It was found that heart rate and behavioral inhibition were positively correlated (0.595), whereas behavioral inhibition was negatively correlated with caregiver attitudes of empathy (−0.356), appropriate expectations (−0.366), and use of positive discipline techniques (−0.275). However, there was no correlation between heart rate and caregiver attitudes. These data suggest that physiological reactivity to novel stimuli and caregiver attitudes of empathy, appropriate expectations, and use of positive discipline techniques conjointly influence behavioral inhibition in early childhood. Further, these three caregiver variables accounted for significant variance in children who had high reactive physiological profiles associated with inhibited behavior patterns, but did not display such patterns. Copyright © 2003 John Wiley & Sons, Ltd.
A longitudinal examination of the transition to symbolic communication in the second year of life
Authors: Camaioni Luigia , Aureli Tiziana , Bellagamba Francesca , Fogel Alan
Published: February 2003

Between 10 and 24 months of age, children progress from communicating through conventional signals to communicating through symbols in a variety of situations. The present study investigates this transition analysing mother–child communication frames and the child's communicative acts, and tracing the developmental changes in both frames and communicative acts. Four children (2 girls, 2 boys) and their mothers were observed longitudinally and extensively, from 10 to 24 months of age, using a multiple case‐study method. Through the detailed investigation of these single cases, clear developmental rajectories were found, showing that conventional frames and representational gestures ‘bridge’ the transition from attentional to symbolic communication. There were significant differences between dyads and children in the developmental trajectories for several frames and communicative acts. The results not only confirm previous findings on the development of verbal and gestural communication, but provide new insights into the transition to symbolic communication in the second year of life, first because of the use of frame analysis and second because of a focus on individual trajectories in development. Copyright © 2003 John Wiley & Sons, Ltd.
Frequent hypermethylation of promoter region of RASSF1A in tumor tissues and voided urine of urinary bladder cancer patients
Authors: Chan Michael W.Y. , Chan Lung W. , Tang Nelson L.S. , Lo Kwok Wai , Tong Joanna H.M. , Chan Anthony W.H. , Cheung Ho Y. , Wong Wai S. , Chan Peter S.F. , Lai Fernand M.M. , To Ka Fai
Published: February 2003

High frequency loss of 3p21.3 region where RASSF1A located was demonstrated in several tumors. We aimed to investigate the methylation status of RASSF1A and the frequency of LOH in 3p21.3 region in bladder cancer. Three bladder cancer cell lines, 40 cases of bladder TCC and 14 cases of paired voided urine samples were subjected to methylation analysis. By methylation specific PCR, complete methylation of promoter region of RASSF1A gene were detected in cell lines T24 and UMUC3. Demethylation treatment re‐expressed RASSF1A in these 2 cell lines. Methylation of RASSF1A was also detected in 47.5% (19/40) of the TCC cases but not in 6 carcinoma in situ (CIS) or 6 normal urothelium samples. For LOH study, loss of 3p21.3 region was detected in 57.9% (11/19) of our cases. Interestingly, methylation of RASSF1A was found in 72.7% (8/11) of the cases with LOH but only in 12.5% (1/8) of the cases without LOH. Methylation of RASSF1A was detected in 50% (7/14) of voided urine samples, but not in normal control. It showed a higher sensitivity than conventional urine cytology in detecting cancer cells, especially for low grade cases. In conclusion, our results demonstrated a high frequency of RASSF1A methylation with frequent LOH in 3p21.3 region in bladder cancer. It suggested that it may be a potential tumor suppressor gene in this chromosomal region and can be silenced by promoter hypermethylation. Detection of aberrant gene methylation in routine voided urine was feasible and may provide a non‐invasive and sensitive approach for cancer detection. © 2003 Wiley‐Liss, Inc.
Expression of SH2D1A in five classical Hodgkin's disease‐derived cell lines
Authors: Kis Loránd L. , Nagy Noémi , Klein George , Klein Eva
Published: February 2003

The Src homology 2 domain protein 1A (SH2D1A) is a small, 128‐amino acid protein consisting of a single SH2 domain; it is probably involved in signal regulation. It is expressed in activated T and natural killer (NK) cells, but not in B lymphocytes. It was discovered in studies on the rare hereditary condition X‐linked lymphoproliferative disease (XLP). Individuals with this condition either lack or carry an altered protein. The serious symptoms (fatal mononucleosis) present almost exclusively at the first encounter with Epstein‐Barr virus (EBV). The absence of SH2D1A in B cells, which are the targets of EBV, has to be reconciled with this clinical situation. In an earlier search for B lymphocytes expressing SH2D1A, we detected it in EBV‐carrying type I Burkitt's lymphoma (BL) lines. We now show SH2D1A in 5 EBV‐negative classical Hodgkin's disease (HD)‐derived cell lines. Two lines belong to the T lineage and 3 to the B lineage. One B‐HD line, which originated from nodular lymphocyte‐predominant Hodgkin's lymphoma and differed in phenotype, was SH2D1A‐negative. This finding is in accordance with the previously reported abundant SH2D1A mRNA in Hodgkin and Reed‐Sternberg (HRS) cells. We thus found SH2D1A expression in lines of malignant origin assigned to the B lineage. Its presence in HRS cells may lead us closer to an understanding of the pathophysiology of the serious syndrome connected with EBV infection in XLP patients, because HRS‐like cells have been detected in the lymphoid tissue of patients with infectious mononucleosis. It is likely therefore that in addition to the demonstrated functional defect of T and NK cells imposed by the SH2D1A mutation, the behavior of certain EBV‐infected B lymphocytes is also modified. © 2003 Wiley‐Liss, Inc.
Decrease of DNA methyltransferase 1 expression relative to cell proliferation in transitional cell carcinoma
Authors: Kimura Fumihiro , Seifert Hans‐Helge , Florl Andrea R. , Santourlidis Simon , Steinhoff Christine , Swiatkowski Sandra , Mahotka Csaba , Gerharz Claus‐Dieter , Schulz Wolfgang A.
Published: February 2003

In many common cancers such as transitional cell carcinoma (TCC), specific genes are hypermethylated, whereas overall DNA methylation is diminished. Genome‐wide DNA hypomethylation mostly affects repetitive sequences such as LINE‐1 retrotransposons. Methylation of these sequences depends on adequate expression of DNA methyltransferase I (DNMT1) during DNA replication. Therefore, DNMT1 expression relative to proliferation was investigated in TCC cell lines and tissue as well as in renal carcinoma (RCC) cell lines, which also display hypomethylation, as indicated by decreased LINE‐1 methylation. Cultured normal uroepithelial cells or normal bladder tissue served as controls. In all tumor cell lines, DNMT1 mRNA as well as protein was decreased relative to the DNA replication factor PCNA, and DNA hypomethylation was present. However, the extents of hypomethylation and DNMT1 downregulation did not correlate. Reporter gene assays showed that the differences in DNMT1 expression between normal and tumor cells were not established at the level of DNMT1 promoter regulation. Diminished DNMT1:PCNA mRNA ratios were also found in 28/45 TCC tissues but did not correlate with the extent of DNA hypomethylation. In addition, expression of the presumed de novo methyltransferases DNMT3A and DNMT3B mRNAs was investigated. DNMT3B overexpression was observed in about half of all high‐stage TCC (DNMT3B vs. tumor stage, χ2: p = 0.03), whereas overexpression of DNMT3A was rarer and less pronounced. Expression of DNMT3A and DNMT3B in most RCC lines was higher than in TCC lines. Our data indicate that DNMT1 expression does not increase adequately with cell proliferation in bladder cancer. This relative downregulation probably contributes to hypomethylation of repetitive DNA but does not determine its extent alone. © 2003 Wiley‐Liss, Inc.
Different tumors in bone each give rise to a distinct pattern of skeletal destruction, bone cancer‐related pain behaviors and neurochemical changes in the central nervous system
Authors: Sabino Mary Ann C. , Luger Nancy M. , Mach David B. , Rogers Scott D. , Schwei Matthew J. , Mantyh Patrick W.
Published: February 2003

Pain is the most common presenting symptom in patients with bone cancer and bone cancer pain can be both debilitating and difficult to control fully. To begin to understand the mechanisms involved in the generation and maintenance of bone cancer pain, we implanted 3 well‐described murine tumor cell lines, 2472 sarcoma, B16 melanoma and C26 colon adenocarcinoma into the femur of immunocompromised C3H‐SCID mice. Although each of the tumor cell lines proliferated and completely filled the intramedullary space of the femur within 3 weeks, the location and extent of bone destruction, the type and severity of the pain behaviors and the neurochemical reorganization of the spinal cord was unique to each tumor cell line injected. These data suggest that bone cancer pain is not caused by a single factor such as increased pressure induced by intramedullary tumor growth, but rather that multiple factors are involved in generating and maintaining bone cancer pain. © 2003 Wiley‐Liss, Inc.
Naive CD8+ T cell recruitment and proliferation are dependent on stage of dendritic cell maturation
Authors: Kaiser Andrew , Bercovici Nadège , Abastado Jean‐Pierre , Nardin Alessandra
Published: February 2003

Dendritic cells (DC) play a crucial role in controlling the initiation and orientation of antigen (Ag)‐specific immune responses. It is widely accepted that optimal T cell priming requires mature DC. Although the molecular events associated with DC activation have been extensively studied, little is known about the consequences of DC maturation on recruitment and expansion of naive T cells. In the present study, we used a model tumor Ag to show that the kinetics of human DC maturation drastically affect the induction of Ag‐specific effector CD8+ T cells. In absence of exogenous cytokines and CD4 help, only DC at early stages of maturation were able to generate high frequencies of CTL. This expansion resulted from both enhanced recruitment and intense proliferation ofT cell precursors and could lead to an increase of up to 1,000‐fold in the final number of effector T cells compared to non‐matured DC. In our model, larger recruitment of naïve CD8+ cells did not modify the overall avidity of the Ag‐specific T cell population.
An improved algorithm to locate critical points in a 3D scalar field as implemented in the program MORPHY
Authors: Malcolm Nathaniel O. J. , Popelier Paul L. A.
Published: February 2003

A new algorithm for location of the critical points in general scalar fields is described. The new method has been developed as part of an on‐going process to exploit the topologic analysis of general 3D scalar fields. Part of this process involves the use of topologic information to seed the critical point search algorithm. The continuing move away from topologic studies of just the electron density requires more general algorithms and the ability to easily “plug in” new functions, for example, the Laplacian of the electron density (▿2ρ), the Electron Localisation Function (ELF), the Localised Orbital Locator (LOL), the Lennard–Jones function (LJF), as well as any new functions that may be proposed in the future. Another important aspect of the current algorithm is the retention of all possible intermediate information, for example, the paths describing the connectivity of critical points, as well as an ability to restart searches, something that becomes increasingly important when analysing larger systems. This new algorithm represents a core part of a new local version of the MORPHY code. We distinguish nine universal types of gradient paths. © 2003 Wiley Periodicals, Inc. J Comput Chem 24: 437–442, 2003
Duplex Doppler sonography of transplant renal artery stenosis
Authors: de Morais Ruth Helena , Muglia Valdair Francisco , Mamere Augusto Elias , Pisi Tânia Garcia , Saber Luciana Tanajura , Muglia Valmir Aparecido , Elias Jorge , Piccinato Carlos Eli , Trad Clóvis Simão
Published: February 2003

Purpose

The aim of this study was to evaluate the accuracy of duplex Doppler sonography in diagnosing transplant renal artery stenosis (TRAS) and to determine which parameter is the most reliable for making that diagnosis.

Methods

Over a 3‐year period, we sonographically evaluated patients who were referred for investigation of possible TRAS. We investigated the following parameters: peak systolic velocity (PSV) in the external iliac and renal arteries, acceleration time and acceleration in the intrarenal arteries, acceleration time in the renal artery, resistance index, and the ratio of the PSVs in the renal and external iliac arteries. We also used MR angiography and digital subtraction arteriography to verify the degree of stenosis. After the evaluations, the patients were classified into 2 groups, 1 with and the other without significant stenosis (> 50% narrowing of the lumen) on digital subtraction arteriography. We also included a control group of patients who had undergone renal transplantation at least 6 months before, had had a good course after transplantation, had a diastolic blood pressure of 90 mm Hg or less, and were taking a maximum of 1 antihypertensive drug.

Results

Our study population consisted of 22 patients suspected to have TRAS (10 without and 12 with confirmed significant stenosis) and 19 control patients. We found statistically significant differences between the mean values of these 3 groups except for the PSV in the iliac artery and the resistance index in the intrarenal arteries. The most accurate parameters to use in diagnosing TRAS were an acceleration time of 0.1 second or higher in the renal and intrarenal arteries, a PSV of greater than 200 cm/second in the renal artery, and a ratio of PSVs in the renal and external iliac arteries of greater than 1.8.

Conclusions

Duplex Doppler sonography is an excellent method for screening patients suspected to have TRAS and can help select which of those patients should undergo digital subtraction arteriography. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:135–141, 2003
The small spleen: Sonographic patterns of functional hyposplenia or asplenia
Authors: Görg Christian , Eichkorn Miriam , Zugmaier Gerhard
Published: February 2003

Purpose

Functional hyposplenia or asplenia (FAS) can be associated with potential fatal infections. The diagnosis of FAS is traditionally made on liver‐spleen scintigraphy and finding Howell‐Jolly bodies within erythrocytes. In this retrospective study, our goal was to identify any characteristic sonographic findings of the spleen in patients with FAS in an attempt to determine whether the diagnosis of FAS can be made sonographically.

Methods

In a review of all medical and sonographic records from the period of January 1, 1985, through December 31, 2001, we identified 24 patients (11 men, 13 women) in whom FAS had been diagnosed by liver‐spleen scintigraphy (n = 13) or the finding of Howell‐Jolly bodies (n = 11). The following sonographic parameters were determined: size of spleen (small, normal, or large), echotexture of the spleen (homogeneous versus inhomogeneous), echogenicity (isoechoic versus hyperechoic), presence of focal splenic lesions, and patterns of splenic vascularization as determined by color Doppler sonography (absent flow, hilar flow, or parenchymal flow).

Results

The spleen was small in 20 patients (83%) and normal in the other 4 (17%). Echotexture was homogeneous in 13 patients (54%) and inhomogeneous in 11 (46%). The spleen was isoechoic in 18 cases (75%) and hyperechoic in 6 (25%). Six patients (25%) had focal lesions. Color Doppler sonography showed absent flow in 4 patients (17%), hilar flow in 17 (71%), and hilar and parenchymal vascularization in 3 (12%).

Conclusions

Sonographic findings in the spleen of patients with FAS are characterized predominantly by a small spleen with absence of parenchymal vascularization on color Doppler sonography in most cases. Future prospective studies will be necessary to confirm these findings and to determine whether FAS can be diagnosed reliably with sonography. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:152–155, 2003
Transcranial Doppler findings in middle cerebral arterial occlusive disease in relation to degree of stenosis and presence of concomitant stenoses
Authors: Bang Oh Young , Cho Jeong Hoon , Han Byung In , Joo In Soo , Kim Dong Ik , Huh Kyoon
Published: February 2003

Purpose

We evaluated the accuracy of transcranial Doppler (TCD) criteria in detecting middle cerebral artery (MCA) stenoses other than solitary severe stenoses.

Methods

Three TCD criteria were evaluated in patients with acute MCA territory infarction who also underwent angiography: abnormalities in mean velocity (MV), focal areas of spectral waveform abnormalities, and compensatory increase in MV in collateral vessels.

Results

Among 102 patients studied, angiography revealed MCA lesions in 48: 16 had uncomplicated lesions (single stenosis of moderate to severe degree), 19 had mildly complicated lesions (single MCA stenosis of other than moderate to severe degree, or moderate to severe MCA stenosis with a concomitant lesion outside the MCA), and 13 had severely complicated lesions (MCA stenosis of other than moderate to severe degree with a concomitant lesion outside the MCA). The sensitivity of abnormalities in MV in uncomplicated MCA lesions was 81%, whereas it was 53% in mildly complicated MCA lesions and 38% in severely complicated MCA lesions. However, a compensatory increase in MV in collaterals was more frequently found in complicated MCA lesions, and focal areas of spectral waveform abnormalities were observed fairly consistently in all groups.

Conclusions

TCD findings of focal areas of spectral waveform abnormalities and compensatory collateral flow were common in complicated MCA lesions and may improve the specificity of TCD in the diagnosis of MCA stenosis. © 2003 Wiley Periodicals, Inc. J Clin Ultrasound 31:142–151, 2003
MRI‐guided access to the retropharynx
Authors: Lai Annie , Maghami Ellie , Borges Alexandra , Bonyadilou Shahram , Curran John , Abemayor Elliot , Lufkin Robert
Published: February 2003

Purpose

To describe MR‐guided access to the retropharynx for precise fine‐needle aspiration cytology (FNAC), and other indications for needle placement.

Materials and Methods

A retrospective review was made of 15 procedures that had been performed on 14 patients. These patients had a retropharyngeal mass on MRI and had undergone MR‐guided minimally invasive access to the retropharynx for either diagnostic or therapeutic intervention in the period of October 1989 to January 2000.

Results

All 14 patients underwent MR‐guided access to the retropharynx for FNAC without immediate or delayed complications. MRI confirmed that the biopsy needle was within the retropharyngeal mass in all patients. MR‐guided FNAC revealed five true‐positive, five true‐negative, four indeterminate, and no false‐positive cases. Ten of the 14 patients (71%) had diagnostic aspirations. In one patient with retropharyngeal extension of carcinoma, an MR‐guided approach was used for the experimental interstitial laser therapy (ILT).

Conclusion

The results suggest that an MR‐guided retromandibular approach to biopsy of retropharyngeal mass is minimally invasive and safe. J. Magn. Reson. Imaging 2003;17:317–322. © 2003 Wiley‐Liss, Inc.
On the synchronization of transcranial magnetic stimulation and functional echo‐planar imaging
Authors: Bestmann Sven , Baudewig Jürgen , Frahm Jens
Published: February 2003

Purpose

To minimize artifacts in echo‐planar imaging (EPI) of human brain function introduced by simultaneous transcranial magnetic stimulation (TMS).

Materials and Methods

Distortions due to TMS pulses (0.25 msec, 2.0 T) were studied at 2.0 T before and during EPI.

Results

Best results were obtained if both the EPI section orientation and the frequency‐encoding gradient were parallel to the plane of the TMS coil. Under these conditions, a TMS pulse caused image distortions when preceding the EPI sequence by less than 100 msec. Recordings with a magnetic field gradient pick‐up coil revealed transient magnetic fields after TMS, which are generated by eddy currents in the TMS coil. TMS during image acquisition completely spoiled all transverse magnetizations and induced disturbances ranging from image corruption to mild image blurring, depending on the affected low and high spatial frequencies. Simultaneous TMS and radio‐frequency (RF) excitation gave rise to T1‐dependent signal changes that lasted for several seconds and yielded pronounced false‐positive activations during functional brain mapping.

Conclusion

To ensure reliable and robust combinations, TMS should be applied at least 100 msec before EPI while completely avoiding any pulses during imaging. J. Magn. Reson. Imaging 2003;17:309–316. © 2003 Wiley‐Liss, Inc.