bluuebunny/crossref_metadata_2025 huggingface dataset:
Tissue microarray‐based studies of patients with lymph node negative breast carcinoma show that met expression is associated with worse outcome but is not correlated with epidermal growth factor family receptors
Authors: Tolgay Ocal Idris , Dolled‐Filhart Marisa , D'Aquila Thomas G. , Camp Robert L. , Rimm David L.
Published: April 2003

BACKGROUND

It has been shown that receptor tyrosine kinases (RTKs) predict outcome in patients with breast carcinoma. Although RTKs are a large family, HER‐2, epidermal growth factor receptor (EGFR), Met (hepatocyte growth factor receptor), and others all have shown the ability to predict outcome. However, it remains unclear whether these markers are defining the same subpopulation of patients with breast carcinoma. In this study, the authors attempted to determine the correlation between RTKs on the basis of their ability to stratify a population according to outcome.

METHODS

The authors used tissue microarray technology to study 324 patients with lymph node negative breast carcinoma who had 20–40 years of follow‐up. Expression was assessed using immunohistochemical stains for Met, EFGR, fibroblast growth factor receptor (FGFR), and HER‐2. Expression levels were assessed by two observers, and correlations were analyzed. Standard pathology information, including tumor size, nuclear grade, Ki‐67 receptor status, and estrogen and progesterone receptor expression levels, also was collected.

RESULTS

RTK expression in the study cohort revealed two strong correlations. Specifically, HER‐2 and EGFR showed similar expression patterns (P < 0.0001), and Met cytoplasmic domain and FGFR cytoplasmic staining showed similar expression patterns (P < 0.0001), but no correlation was found between the two groups. Of these RTKs, only high levels of Met cytoplasmic domain showed significance as a prognostic marker defining a shortened survival compared with the rest of the population (P = 0.0035; relative risk, 2.04). In the same group of patients, HER‐2, hormone receptor status, and other RTK family receptors were not correlated with outcome. In multivariate analysis, only Met cytoplasmic domain and tumor size showed independent predictive value.

CONCLUSIONS

The current results indicate that the cytoplasmic domain of Met shows a unique staining pattern and defines a set of patients unique from the set of patients defined by overexpression of HER‐2, EGFR, or hormone receptors. Furthermore, this group of patients is associated tightly and independently with worse outcome. Cancer 2003;97:1841–8. © 2003 American Cancer Society.

DOI 10.1002/cncr.11335
Plasticity in the tonotopic organization of the medial geniculate body in adult cats following restricted unilateral cochlear lesions
Authors: Kamke Marc R. , Brown Mel , Irvine Dexter R.F.
Published: April 2003

To investigate subcortical contributions to cortical reorganization, the frequency organization of the ventral nucleus of the medial geniculate body (MGv) in six normal adult cats and in eight cats with restricted unilateral cochlear lesions was investigated using multiunit electrophysiological recording techniques. The tonotopic organization of MGv in the lesioned animals, with severe mid‐to‐high frequency hearing losses, was investigated 40–186 days following the lesioning procedure. Frequency maps were generated from neural responses to pure tone bursts presented separately to each ear under barbiturate anesthesia. Consideration of the frequency organization in normal animals, and of the apparently normal representation of the ipsilateral (unlesioned) cochlea in lesioned animals, allowed for a detailed specification of the extent of changes observed in MGv. In the lesioned animals it was found that, in the region of MGv in which mid‐to‐high frequencies are normally represented, there was an “expanded representation” of lesion‐edge frequencies. Neuron clusters within these regions of enlarged representation that had “new” characteristic frequencies displayed response properties (latency, bandwidth) very similar to those in normal animals. Thresholds of these neurons were not consistent with the argument that the changes merely reflect the residue of prelesion responses, suggesting a dynamic process of reorganization. The tonotopic reorganization observed in MGv is similar to that seen in the primary auditory cortex and is more extensive than the reorganization found in the auditory midbrain, suggesting that the auditory thalamus plays an important role in cortical plasticity. J. Comp. Neurol. 459:355–367, 2003. © 2003 Wiley‐Liss, Inc.
Static and dynamic analysis of an aerofoil bladed disc using the concept of cyclic symmetry
Authors: Vaidyanathan Ramnath , Santhanam Shriram , Ramamurti V.
Published: April 2003

Centrifugal fan impellers with aerofoil blades are analysed using the concept of cyclic symmetry. Impellers with single cover plate alone are considered. Both static and dynamic analyses are done and user‐friendly programs for the design of these impellers are developed. In addition, parametric studies were also undertaken. Variations of maximum stress and the lowest frequency with the various values of both the outer diameter and thickness of the impeller plates was carried out, and the results plotted. Copyright © 2003 John Wiley & Sons, Ltd.
Theoretical analysis of subtractive color mixture characteristics
Authors: Matsushiro Nobuhito , Ohta Noboru
Published: April 2003

Understanding the characteristics of the stimulus values of colors obtained by subtractive color mixture is not easy, compared with those obtained by additive color mixture, since the relationship between superimposed absorption media and the stimulus values is not simple. In this article, using the assumption of the Lambert‐Beer model for subtractive color mixture, we prove several theorems regarding the stimulus values of colors obtained by subtractive color mixture. Although these theorems are proved theoretically, numerical illustrations are also shown to confirm the theorems. The results of this paper will contribute to a systematization of subtractive color mixture. © 2003 Wiley Periodicals, Inc. Col Res Appl, 28, 175–181, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/col.10143
Boundary integral equations for computer‐aided design of Y‐branch circuits of quantum electron waveguide
Authors: Katayama Kiyofumi , Tanaka Masahiro , Tanaka Kazuo
Published: April 2003

With a view to contributing to the fundamental theory of the computer‐aided design of electron waveguide circuits, the guided‐mode extracted boundary integral equation derived earlier by the authors is now extended to three‐port Y‐branch circuits. The integral equation formulated as a rigorous boundary value problem of the Y‐branch circuits can be directly analyzed numerically by using only the boundary element method (moment method) without mode‐expansion. If the electron energy is larger or smaller than the external potential of the waveguide, almost identical algorithms can be used for coding. A specific example of the Y‐branch electron waveguide with a finite external potential is analyzed and the mathematical validity of the derived integral equation and the effectiveness of the analysis method are studied. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(5): 16–25, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10108
Experimental study on oscillation characteristics of magnetron after turning off filament current
Authors: Mitani Tomohiko , Shinohara Naoki , Matsumoto Hiroshi , Hashimoto Kozo
Published: April 2003

The objective of the present research is the application of a magnetron made for civilian use to a transmitter for a microwave power transmission system, including the solar power station/satellite (SPS) concept. Experiments show that, when a magnetron is made to oscillate with a DC stabilized power supply drive, the oscillation frequency spectrum becomes narrower, although the DC‐RF conversion efficiency suffers somewhat if the filament current is turned off after oscillation than when the specified filament current flows in the thermal emission filament. The reasons for a narrower oscillation frequency spectrum are elimination of the disturbance of the anode current caused by the anode current–anode voltage relationship, one of the oscillation characteristics of the magnetron, and reduction of the thermal effect on electrons. By improvement of the frequency spectrum, it is now possible to configure a phased array system with high output, high efficiency, and low cost by means of a magnetron. Hence, a future application to SPS is expected. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 2, 86(5): 1–9, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjb.10116
Estimation of frequency offset in QPSK demodulation
Authors: Obote Shigeki , Kagoshima Kenichi
Published: April 2003

If there is a frequency offset in the local oscillator circuit in QPSK demodulation, the BER is degraded. Previously, methods for estimating this frequency offset have been proposed. However, few techniques that have been studied can estimate this offset in an environment with a large frequency offset or noise. A digital adaptive IIR notch filter is effective for estimation of a large frequency offset in an environment with noise. However, the noise is colored in the receiver due to the IF band BPF inserted in order to suppress out‐of‐band noise. Therefore, the converged value has a bias error with respect to the target value. The method proposed in this paper is based on the fact that the phase of the digital IIR‐BPF is zero at the center frequency of the amplitude characteristic. This characteristic is used for control by applying a negative feedback to the digital IIR‐BPF coefficients. Then, no bias error is generated because the noise in the in‐phase channel and that of the quadrature channel in QPSK are uncorrelated. Further, the proposed method does not drift but maintains the present status due to the uncorrelated character described above, even in the case of channel disconnection such as shadowing. Therefore, this is a frequency offset estimation method suitable for mobile communications. As a result of evaluation of the proposed method in terms of the BER in a white Gaussian noise channel, it is confirmed that the proposed method provides a BER lower than that of the conventional digital adaptive IIR notch filter. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 3, 86(9): 1–12, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecjc.10089
Clinical and immunological evaluation of patients with metastatic melanoma undergoing immunization with the HLA‐Cw*0702‐associated epitope MAGE‐A12:170–178
Authors: Bettinotti Maria P. , Panelli Monica C. , Ruppe Erin , Mocellin Simone , Phan Giao Q. , White Donald E. , Marincola Francesco M.
Published: April 2003

Patients with metastatic melanoma who expressed HLA‐Cw*0702 and whose tumors had demonstrable MAGE‐A12 expression were immunized with the peptide MAGE‐A12:170–178 administered subcutaneously in incomplete Freund's adjuvant (IFA). The peptide was administered either every week or every 3 weeks for 4 cycles. Patients were evaluated for toxicity and for immunologic and clinical response to peptide immunization. Pre‐treatment fine needle aspirates were obtained to document MAGE‐A12 expression for enrollment. MAGE‐A12 mRNA was identified in 62% of specimens. Nine patients were selected for vaccination based on MAGE‐A12 expression and the presence of HLA‐Cw*0702. The immune response was monitored both by tetrameric HLA‐Cw*0702/MAGE‐A12:170–178 complexes and by analysis of interferon‐γ mRNA transcription using a quantitative real‐time polymerase chain reaction assay after peptide‐specific stimulation. The samples consisted of circulating lymphocytes analyzed ex vivo or after 10 to 14 days of in vitro sensitization. One of 9 patients sustained an ongoing partial clinical response. No convincing evidence of enhancement of the systemic immune response against MAGE‐A12:170–178 could be documented. Because of the modest immunological and clinical results, the present protocol has been discontinued as new routes of administration are being considered. © 2003 Wiley‐Liss, Inc.
Novel alternatively spliced variant with a deletion of 52 BP in exon 6 of the progesterone receptor gene is observed frequently in breast cancer tissues
Authors: Hisatomi Hisashi , Kohno Norio , Wakita Kazuyuki , Nagao Kumi , Hirata Hiroyuki , Hikiji Kazumasa , Harada Shoji
Published: April 2003

The human progesterone receptor (PR) is a ligand‐activated nuclear transcription factor that mediates progesterone action in target tissues. We found a novel alternatively spliced variant (ASV) of the PR mRNA in breast cancer tissues. The deleted transcript was characterized by an out‐of‐frame deletion of 52 bp in exon 6 (PR delta6/2 ASV). The PR delta6/2 ASV mRNA results in a partial defect in the region of the ligand‐binding domain of the hormone receptor, where conserved residues are missing from the core of the protein. To clarify the clinical significance of the PR delta6/2 ASV, we investigated the expression of this ASV in noncancerous and cancerous tissues from patients with breast cancer using RT‐PCR. The novel PR delta6/2 mRNA was detected in 24 of 39 (61.5%) cancerous tissues and in 3 of 39 (7.7%) noncancerous tissues from patients with breast cancer. PR delta6/2 ASV mRNA was expressed more frequently in breast cancer tissues than in noncancerous tissues (p < 0.0001), which suggests a possible relationship between the expression of PR delta6/2 and breast cancer. Our observations may provide a novel strategy for the genetic diagnosis of breast cancer. © 2003 Wiley‐Liss, Inc.
CS‐1, a novel c‐kithi+ acute myeloid leukemia cell line with dendritic cell differentiation capacity and absent immunogenicity
Authors: Erben Ulrike , Thiel Eckhard , Bittroff‐Leben Alexandra , Schoch Claudia , Fichtner Iduna , Dürkop Horst , Notter Michael
Published: April 2003

Complex cytogenetic abnormalities confer dismal prognoses in myeloid malignancies. Even bone marrow transplantation from siblings or matched unrelated donors offer minimal chances for cure, suggesting that these cases are not only refractory to chemotherapy but also resist the graft‐vs.‐leukemia effect. We herein describe the first permanent, factor‐independent c‐kithi+ cell line CS‐1 derived from an unrelated donor stem cell transplanted patient with relapsed acute myeloid leukemia (AML)‐M5a of high‐risk karyotype [monosomy 7, t(2;11)(q31;p13), t(10;12)(q24;q24)]. Having the same karyotype, CS‐1 exhibits an autonomous growth pattern and responds to stem cell factor (SCF). CS‐1 did not induce T cell activation in mixed‐lymphocyte‐tumor‐cultures (MLTCs) and, when used as third party stimulators, decreased T cell proliferation in mixed‐lymphocyte reactions (MLRs). Cytokines added exogenously or secreted from bystander T cells caused CS‐1 to differentiate into dendritic cells (DCs). CS‐1‐derived DCs, in contrast to DCs originating from non‐malignant CD34+ progenitor cells, had virtually no T cell stimulatory effect, indicating that CS‐1 is both immunosuppressive and poorly immunogenic. These properties may partially be due to the detected downregulation of costimulatory molecules and appear to involve a soluble factor. CS‐1 cells injected subcutaneously (s.c.) to non‐obese diabetes/severe combined immunodeficient (NOD/SCID) mice produced solid tumors, disseminating into bone marrow and spleen. The data show that transforming AML blasts with high‐risk karyotype into DCs is insufficient to restore their immunogenicity and that the CS‐1 cell line is useful to identify tumor‐related immunosuppressive mechanisms in vitro and in vivo. © 2003 Wiley‐Liss, Inc.
Efficient tumor cell lysis by autologous, tumor‐resident T lymphocytes in primary ovarian cancer samples by an EP‐CAM‐/CD3‐bispecific antibody
Authors: Wimberger Pauline , Xiang Wei , Mayr Doris , Diebold Joachim , Dreier Torsten , Baeuerle Patrick A. , Kimmig Rainer
Published: April 2003

The epithelial cell adhesion molecule (Ep‐CAM) is expressed on the surface of most human carcinomas, including ovarian, breast, lung, prostate and colorectal carcinoma. Ep‐CAM was shown to be a valid target for monoclonal antibody‐based therapies. We have investigated whether an Ep‐CAM‐/CD3‐bispecific single‐chain antibody called bscEp‐CAM × CD3 is effective in tumor cell elimination within the cellular microenvironment of primary ovarian cancer tissue. The ex vivo elimination of ovarian cancer cells in tumor preparations from 21 patients was monitored by flow cytometry using Ep‐CAM/CA‐125 double‐labeling or Ep‐CAM single‐labeling combined with propidium iodide uptake of cells. Methodology was established by the ovarian cancer cell line OvCAR. A total of 17 (81%) patient samples showed a dose‐dependent tumor cell elimination by bscEp‐CAM × CD3. High and specific tumor cell lysis was seen at bscEp‐CAM × CD3 concentrations as low as 1 ng/ml, at very low effector:target ratios and in the absence of T cell costimulation. The high efficacy of the bispecific antibody may be due to the non‐restricted activation of tumor‐resident cytotoxic T lymphocytes. In clinical trials, the ex vivo data with the T cell‐recruiting bispecific antibody bscEp‐CAM × CD3 may translate into a high response rate and efficacy of tumor cell elimination. © 2003 Wiley‐Liss, Inc.
Farnesyl transferase inhibitor SCH66336 is cytostatic, pro‐apoptotic and enhances chemosensitivity to cisplatin in melanoma cells
Authors: Smalley Keiran S.M. , Eisen Tim G.
Published: April 2003

The constitutive activity of a number of growth and cell survival pathways are thought to contribute to the inherent resistance of melanoma to chemotherapy and radiotherapy. Many of these pathways are driven through the small GTPase Ras. Novel drugs such as the farnesyl transferase inhibitors (FTIs) and farnesyl thiosalicylic acid (FTS) interfere with the signaling of oncogenic Ras. The aim of our study was to assess the anti‐tumour activity of the FTI SCH66336 in melanoma and to assess whether SCH66336 and FTS could modulate chemoresistance in melanoma cells. SCH66336 had marked anti‐proliferative activity in both human and mouse melanoma cell lines, but not in non‐transformed NIH 3T3 cells. The anti‐proliferative activity of SCH66336 was due to G1‐phase cell cycle arrest and retinoblastoma protein inactivation, followed by apoptosis. Cisplatin, when administered alone, induced little apoptosis. In combination with cisplatin, both FTS and SCH66336 markedly enhanced the level of cisplatin‐induced apoptosis, an effect that was associated with enhanced G2/M cell cycle arrest. Pharmacological inhibitors of either ERK or PI‐3 kinase/Akt did not mimic the chemosensitising activity of either SCH66336 or FTS. In summary, our study demonstrates that SCH66336 has good in vitro anti‐tumour activity in both human and mouse melanoma cell lines, and suggests that Ras antagonists could be useful in overcoming chemoresistance to cisplatin in melanoma. © 2003 Wiley‐Liss, Inc.
Association of cyclin D1 (G870A) polymorphism with susceptibility to esophageal and gastric cardiac carcinoma in a northern Chinese population
Authors: Zhang Jianhui , Li Yan , Wang Rui , Wen Denggui , Sarbia Mario , Kuang Gang , Wu Mingli , Wei Lizhen , He Ming , Zhang Liwei , Wang Shijie
Published: April 2003

Our aim was to investigate the association of cyclin D1 (G870A) single nucleotide polymorphism with susceptibility to esophageal and cardiac carcinoma in a northern Chinese population. By polymerase chain reaction‐single strand conformation polymorphism analysis, cyclin D1 (G870A) genotyping was carried out among 120 patients with esophageal squamous cell carcinoma (ESCC), 87 patients with gastric cardiac adenocarcinoma (CAC), and 183 age‐ and gender‐matched controls. The cyclin D1 genotype distribution among ESCC patients was significantly different from that among healthy controls (χ2 = 7.372, p = 0.025). The G/G genotype was significantly less frequent among ESCC patients (9.2%) than among healthy controls (20.8%) (χ2 = 7.192, p = 0.007). The G/G genotype significantly reduced risk for the development of ESCC compared to the combination of G/A and A/A genotypes (adjusted odds ratio [OR] = 0.37, 95% confidence interval [CI] = 0.16–0.83). After stratification according to smoking status, the A/A frequency among smoking ESCC (34.3%) and CAC patients (35.7%) was significantly higher than that among smoking healthy controls (18.6%) (χ2 = 5.426 and 5.599, p = 0.020 and 0.018, respectively). Smokers with the A/A genotype had an about 2‐fold increased risk for both of ESCC and CAC compared to the G/A and G/G genotypes, with an adjusted OR of 2.26 in ESCC (95% CI = 1.14–4.49) and of 2.42 in CAC (95% CI = 1.17–4.98). No correlation between the cyclin D1 genotype and development of ESCC or CAC was found among nonsmokers. Determination of the cyclin D1 (G870A) single nucleotide polymorphism may be suitable to identify individuals with increased risk for ESCC or CAC in the northern Chinese population. © 2003 Wiley‐Liss, Inc.
Determination of a minimal region of loss of heterozygosity on chromosome 18q21.33 in osteosarcoma
Authors: Johnson‐Pais Teresa L. , Nellissery Maggie J. , Ammerman Donald G. , Pathmanathan Dharmini , Bhatia Pardeep , Buller Carolyn L. , Leach Robin J. , Hansen Marc F.
Published: April 2003

Previous analysis of tumor‐specific constitutional LOH had identified a putative tumor‐suppressor gene (LOH18CR) active in osteosarcoma tumorigenesis, which mapped to a subregion of chromosome 18q linked to both familial Paget's disease and FEO. Using 9 new polymorphic loci within the previous minimal region of LOH, we have reduced the minimal region of LOH in osteosarcoma tumors to localize the LOH18CR locus to the distal end of chromosome 18q21.33. This new region is approximately 500 kb and contains at least 7 known genes; however, it excludes 2 previous candidate genes: TNFRSF11A (RANK) and BCL2. © 2003 Wiley‐Liss, Inc.
Influence of storage regime prior to abrasion on surface topography of restorative materials
Authors: Turssi Cecilia Pedroso , Hara Anderson Takeo , Magalhães Cláudia Silami de , Serra Mônica Campos , Rodrigues Antonio Luiz
Published: April 2003

This investigation was carried out to evaluate the effect of storage conditions prior to brushing simulation on surface texture of restorative materials. One resin‐modified glass ionomer (Fuji II LC Improved/GC Corp.), one polyacid‐modified composite resin (Dyract AP/Denstply), one microfill composite (Durafill VS/Kulzer), and one hybrid (Filtek–Z250/3M) composite were tested. Forty‐five standardized cylindrical specimens of each material were made and randomly divided into three groups according to their subsequent storage conditions: distilled deionized water, artificial saliva, or pH‐cycling regime. After 24 h, the experimental units were finished and polished and the surface roughness was measured to obtain Ra baseline values (Bv). Samples were subjected to their assigned storage regime and brushed afterwards. By the end of 10 repetitions of this protocol, final surface roughness readings (Fv) were taken. The analysis of covariance (α = 0.05), considering the covariate Bv showed a significant interaction between restorative material and storage condition (pvalue = 0.0002). Tukey's test revealed that the pH‐cycling model provided a significantly lower surface roughness for Fuji II LC and Dyract AP than did the other media. For both composites no significant difference among storage regimes was detected. Under a condition simulating dynamic variation in pH prior to abrasion, the resultant surface texture may be either smoothed down or unchanged, depending on the restorative material, when compared to the effect provided by artificial saliva and distilled deionized water. © 2003 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 65B: 227–232, 2003
Preparation via coligand exchange and characterization of [99mTc‐EDDA‐HYNIC‐D‐Phe1,Tyr3]Octreotide (99mTc–EDDA/HYNIC–TOC)
Authors: von Guggenberg Elisabeth , Sarg Bettina , Lindner Herbert , Melendez Alafort Laura , Mather Stephen J. , Moncayo Roy , Decristoforo Clemens
Published: April 2003

[99mTc‐EDDA–HYNIC‐D‐Phe1,Tyr3]octreotide (99mTc‐EDDA/HYNIC–TOC) is a promising new agent with the potential to replace [111In‐DTPA‐D‐Phe1]‐octreotide in somatostatin receptor scintigraphy. This hydrazinonicotinic acid derivatized somatostatin complex contains ethylenediamine N,N′ diacetic acid (EDDA) as a coligand resulting in a high in vitro and in vivo stability. Since direct 99mTc‐labelling of HYNIC–TOC with EDDA results in low labelling yields, in this study we describe the preparation of 99mTc‐EDDA/HYNIC‐TOC via coligand exchange from Tricine for EDDA. Exchange of coligands is achieved at elevated temperature and under optimized conditions of pH, EDDA concentration and stannous ion. High labelling yields (mean 95.9%) were achieved at high specific activities (>37GBq/µmol). Characterization via HPLC, receptor binding and LC–MS of the resulting complex is described. The formulation developed enables rapid and simple labelling of 99mTc‐EDDA/HYNIC–TOC in a manner suitable for a clinical setting. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and characterization of new 99mTc‐radiopharmaceuticals with dithiobenzoate derivatives for the study of septic inflammatory processes
Authors: Mevellec F. , Roucoux A. , Noiret N. , Moisan A. , Patin H. , Duatti A.
Published: April 2003

Improved methods for the preparation of 99mTc‐radiopharmaceuticals containing dithiobenzoate ligands, in sterile and pyrogen free conditions, are described. These procedures are based on the reaction of these ligands either with [99mTc] pertechnetate in the presence of a strong reducing agent (HCl/tertiary phosphine, SnCl2·2H2O), or with pre‐reduced complexes obtained from different kit formulations. All the preparations led to the high‐yield formation of the neutral and lipophilic 99mTc‐complex [99mTc][Tc(S3CPh)2(S2CPh)], which is analogous to the corresponding compounds obtained with rhenium and the long‐lived β‐emitting isotope technetium‐99 g recently described. HPLC analysis and thin layer chromatography were used to confirm the characterisation of the resulting 99mTc‐radiopharmaceutical which was found to be potentially suitable for blood‐cell labelling as applied to the diagnosis of inflammatory processes. Copyright © 2003 John Wiley & Sons, Ltd.
Tritium‐labelled 8‐cyclopentyl‐3‐(3‐fluoropropyl)‐1‐propylxanthine ([3H]CPFPX), a potent and selective antagonist for the A1 adenosine receptor
Authors: Holschbach Marcus H. , Wutz Walter , Schüller Manfred , Bier Dirk , Coenen H.H.
Published: April 2003

The reduction of 1‐allyl‐8‐cyclopentyl‐3‐(3‐fluoropropyl)xanthine, 7, with tritium gas catalyzed by 10% Pd‐C gave 8‐cyclopentyl‐3‐(3‐fluoropropyl)‐1‐[2,3‐3H]propylxanthine ([3H]CPFPX), 8*, a potent and selective antagonist for the A1 adenosine receptor (A1AR). The synthesis of 7 proceeded from 6‐aminouracil, 1, which underwent silylation and alkylation with allyl bromide to form 6‐amino‐3‐allyluracil, 2. Nitrosation led to the 5‐nitroso compound, 3, which underwent reduction to the 4,5‐diaminouracil, 4, and carbodiimide‐mediated acylation with cyclopentanecarboxylic acid produced 3‐allyl‐6‐amino‐5‐cyclopentylcarboxamidouracil, 6. Alkylation at N−1 with 3‐fluoro‐1‐bromopropane and cyclization with alkali completed the synthesis of 7. [3H]CPFPX had a radiochemical purity of > 98% and a specific activity of >2.1 TBq/mmol (57 Ci / mmol). [3H]CPFPX bound to the rat, pig and human A1AR with a KD of 0.63, 1.37 and 0.71 nM, respectively. The KD at the rat and human A2AAR was 812 and 940 nM, respectively, thus giving selectivities of >1200‐ and >700‐fold. Copyright © 2003 John Wiley & Sons, Ltd.
Circular waveguides with Kronig–Penney morphology as photonic band‐gap filters
Authors: Gómez Álvaro , Solano Miguel A. , Lakhtakia Akhlesh , Vegas Angel
Published: April 2003

Guided wave propagation in a circular waveguide filled with dielectric materials in the Kronig–Penney morphology is theoretically examined. Allowed and forbidden frequency bands in these ideal photonic band‐gap (PBG) structures are obtained for the TEz and TMz propagation modes by invoking the Bloch theorem. Results show the many engineering possibilities for designing electromagnetic filters for ideal structures. Filtering by real PBG structures with a finite number of unit cells is also studied by using the scattering matrix technique. As the number of unit cells in a real filter increases, its transmission characteristics converge to those of its ideal analog in the forbidden frequency bands. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 37: 316–321, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10906
Rigorous analysis of conformal microstrip patch antennas using the FDTD method
Authors: El Brak Mohamed , Essaaidi Mohamed
Published: April 2003

This paper investigates the characteristics of conformal microstrip patch antennas using the rigorous FDTD approach based on a rectangular mesh and a staircase discretization scheme for the curved regions. It is shown that the conformal shape of microstrip patch antennas can be used as another geometrical parameter to allowing their performance to be monitored. Numerical results illustrate the effects of this parameter on the resonant frequencies, return loss, and input impedance of such antennas. © 2003 Wiley Periodicals, Inc. Microwave Opt Technol Lett 37: 372–376, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.10922
Cacalolides from Senecio barba‐johannis
Authors: Burgueño‐Tapia Eleuterio , Joseph‐Nathan Pedro
Published: April 2003

From the roots of Senecio barba‐johannis DC, the two new cacalolides 13‐acetoxycacalohastin (2) and 13‐hydroxy‐14‐oxocacalohastin (3), together with the known cacalolide 13‐acetoxy‐14‐oxocacalohastin (4) were isolated. Their structures were determined on the basis of chemical and spectroscopic evidence. Complete 1H and 13C NMR chemical shift assignments of these compounds were achieved using one‐ and two‐dimensional NMR methods, including gHMQC and gHMBC experiments. Copyright © 2003 John Wiley & Sons, Ltd.
New atranones from the fungus Stachybotrys chartarum
Authors: Hinkley Simon F. , Moore Jennifer A. , Squillari Jennifer , Tak Heekyung , Oleszewski Ryan , Mazzola Eugene P. , Jarvis Bruce B.
Published: April 2003

Four new atranones were isolated from a culture of the filamentous fungus Stachybotrys chartarum. In addition, several ketal derivatives of the hemiketal atranones were prepared. The structures of these new compounds were elucidated based almost entirely on NMR spectroscopic evidence. Copyright © 2003 John Wiley & Sons, Ltd.
Observational study of ACE inhibitor prescribing habits of diabetes physicians in the UK
Authors: Bickerton A , Higgins B , Cummings MH
Published: April 2003

ACE inhibitors are recognised as playing an increasingly pivotal role in the prevention and treatment of diabetic complications, although prescribing remains controversial. The aim of this study was to assess current practice in the prescribing of ACE inhibitors for patients with type 1 or type 2 diabetes.

A simple postal questionnaire was devised to examine ACE inhibitors prescribing habits for patients with diabetes and was sent to all diabetologists in England, Wales and Northern Ireland.

The response rate to the questionnaire was 57% (220/389 replies). Significant differences between ACE inhibitor prescribing in type 1 and type 2 diabetes were observed in patients with hypertension (92.3% first‐line therapy in type 1 diabetes versus 72% in type 2 diabetes, p < 0.001), microalbuminuria (95.5 versus 52.9%, p > 0.001) and retinopathy (30.3 versus 19%, p > 0.001). Less than 10% of clinicians advocated the use of ACE inhibitors for patients with the cardiovascular risk factors (other than hypertension and microalbuminuria) defined as entry criteria in the MICRO‐HOPE study. In the context of acute myocardial infarction (MI), 96% of physicians would use an ACE inhibitor in the presence of clinical heart failure, 60% would use an ACE inhibitor for uncomplicated anterior MI and 30% would use an ACE inhibitor in an uncomplicated inferior MI. Few respondents would investigate for renal artery stenosis prior to commencing ACE inhibitors. However, there was a significant difference in responses depending on type of diabetes (5 versus 9.5%, p > 0.004). 87.5% of clinicians would monitor renal function within a month of the introduction of ACE inhibitors and there was a heterogeneous response to the concentration of serum creatinine resulting in drug withdrawal in the context of deteriorating renal function (within normal range to normal range + 150µmol/L). 10.2% of respondents had withdrawn the drug due to erectile dysfunction and 2.5% due to hypoglycaemia. The most commonly prescribed ACE inhibitors were lisinopril (70.3%), ramipril (54.6%) and perindopril (40.5%).

Although some consensus of opinion regarding the prescription of ACE inhibitors in the management of diabetes exists, there are many areas in which the lack of conclusive evidence results in considerable variation in clinical practice. Copyright © 2003 John Wiley & Sons, Ltd.
Clinical use of glucose sensors in the treatment of diabetes in children and adolescents
Authors: Ludvigsson J , Isacson E
Published: April 2003

In spite of active treatment it is very difficult to achieve good metabolic control and avoid wide fluctuations in blood glucose, especially in insulin‐deficient type 1 diabetic children and adolescents. Even the most intense self‐monitoring of blood glucose gives just a glimpse of the full picture, and we usually know very little about glucose concentrations during the night. The MiniMed glucose sensor has been shown to be a helpful device, providing valuable information on which adjustment of treatment can be based and acting as an educational and motivating tool. Case studies illustrate how the glucose sensor can be used. Copyright © 2003 John Wiley & Sons, Ltd.
Crystal structure of poly(ω‐pentadecalactone)
Authors: Gazzano Massimo , Malta Viscardo , Focarete Maria Letizia , Scandola Mariastella , Gross Richard A.
Published: April 2003

The crystal structure of poly(ω‐pentadecalactone) (PPDL) synthesized by enzyme‐catalyzed polymerization was determined by full‐profile refinement. A pseudo‐orthorombic monoclinic unit cell with dimensionsa= 7.49(1),b= 5.034(9), andc= 20.00(4)Å (fiber axis), and α = 90.06(4)° hosts two monomeric units belonging to polymer chains with opposite orientation, according to the P21space‐group symmetry. A close similarity to the crystal structure of poly(ϵ‐caprolactone) was evident. However, the even number of backbone atoms in the monomer unit of PPDL leads to a lower crystal symmetry. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1009–1013, 2003
Surface modification of magnetic metal nanoparticles and its influence on the performance of polymer composites
Authors: Rong Min Zhi , Zhang Ming Qiu , Wang Hong Bing , Zeng Han Min
Published: April 2003

To control the interfacial interaction in magnetic metal nanoparticles‐filled polymer composites, surfaces of iron, cobalt, and nickel nanoparticles were grafted by irradiation‐induced polymerization. On the basis of the study of dynamical mechanical behavior, thermal stability, and magnetic performance of the composites prepared by either solution mixing or in situ polymerization, the structure–property relationships of the composites are a function of interfacial interaction and the dispersion state of the nanoparticles. In addition, grafting of polymers onto the surface of the metal nanoparticles changed the surface magnetic state, leading to the possibility of purposely tailoring the magnetic behavior of the composites. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1070–1084, 2003
Dielectric relaxational behavior of poly(diitaconate)s containing cyclic rings in the side chain
Authors: Díaz‐Calleja R. , García‐Bernabé A. , Sánchez‐Martínez E. , Sanchis M. J. , Hormazábal E. A. , Gargallo L. , Radić D.
Published: April 2003

Dielectric relaxations of several poly(diitaconate)s with cyclobutyl, cycloheptyl, and cyclooctyl groups in the side chain were investigated. The study was performed by determining the dielectric permittivity and loss, depending on the frequency and temperature. Dynamic dielectric measurements indicated several relaxations according to the chemical structure of the polymers. The dielectric behavior of these polymers was compared with those of poly(dicyclohexyl itaconate), previously reported. The α relaxations were analyzed with the Havriliak–Negami equation. Significant differences in the subglass relaxations were observed. A tentative explanation of the molecular origin of each absorption was proposed in terms of the number of carbon atoms of the ring and their conformational versatility. Strong conductive processes were observed in these polymers at low frequencies and high temperatures. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 1059–1069, 2003
Effects of detergents on the secondary structures of prion protein peptides as studied by CD spectroscopy
Authors: Kuroda Yoshihiro , Maeda Yoshitaka , Sawa Shinichi , Shibata Kiyohiro , Miyamoto Kazuhide , Nakagawa Terumichi
Published: April 2003

Pathogenic prion proteins (PrPSc) are thought to be produced by α‐helical to β‐sheet conformational changes in the normal cellular prion proteins (PrPC) located solely in the caveolar compartments. In order to inquire into the possible conformational changes due to the influences of hydrophobic environments within caveolae, the secondary structures of prion protein peptides were studied in various kinds of detergents by CD spectra. The peptides studied were PrP(129–154) and PrP(192–213); the former is supposed to assume β‐sheets and the latter α‐helices, in PrPSc. The secondary structure analyses for the CD spectra revealed that in buffer solutions, both PrP(129–154) and PrP(192–213) mainly adopted random‐coils (∼60%), followed by β‐sheets (30%–40%). PrP(129–154) showed no changes in the secondary structures even in various kinds of detergents such as octyl‐β‐D‐glucopyranoside (OG), octy‐β‐D‐maltopyranoside (OM), sodium dodecyl sulfate (SDS), Zwittergent 3–14 (ZW) and dodecylphosphocholine (DPC). In contrast, PrP(192–213) changed its secondary structure depending on the concentration of the detergents. SDS, ZW, OG and OM increased the α‐helical content, and decreased the β‐sheet and random‐coil contents. DPC also increased the α‐helical content, but to a lesser extent than did SDS, ZW, OG or OM. These results indicate that PrP(129–154) has a propensity to adopt predominantly β‐sheets. On the other hand, PrP(192–213) has a rather fickle propensity and varies its secondary structure depending on the environmental conditions. It is considered that the hydrophobic environments provided by these detergents may mimic those provided by gangliosides in caveolae, the head groups of which consist of oligosaccharide chains containing sialic acids. It is concluded that PrPC could be converted into a nascent PrPSc having a transient PrPSc like structure under the hydrophobic environments produced by gangliosides. Copyright © 2003 European Peptide Society and John Wiley & Sons, Ltd.
Time‐dependent density functional theory calculations on the chiroptical properties of rubroflavin: Determination of its absolute configuration by comparison of measured and calculated CD spectra
Authors: Wang Yuekui , Raabe Gerhard , Repges Charlotte , Fleischhauer Jörg
Published: April 2003

The absolute configuration of rubroflavin has been determined by comparison of its measured and calculated CD spectra. For this purpose the structures of 30 plausible isomers of the title compound have been optimized with density functional theory (DFT/BP86) using a triple‐zeta valence basis set. The absolute (S) configuration at the S(O)CH3 group has been assumed in these calculations. One quinoid isomer, which is separated from all other structures by an energy gap of about 4 kcal/mol, was found to be the most stable species and to dominate the CD spectrum. The structure of this isomer has been reoptimized under the influence of a solvent using an electrostatic model (COSMO). Based on the geometries of the most stable isomer obtained in the presence and absence of the solvent the excitation energies and oscillator as well as rotational strengths have then been calculated using time‐dependent DFT (TDDFT/TZVP/BP86). Comparison of the measured CD spectrum with that calculated for the energetically lowest isomer shows that especially the long wavelength parts of the spectra agree fairly well as far as the wavelengths and the signs of the Cotton effects are concerned while the correspondence between calculated and measured intensities is less satisfying. The agreement between the measured and calculated spectrum is better if the geometry optimized under the influence of the solvent is used. A detailed analysis of the spectra led us to the conclusion that the absolute configuration of rubroflavin is (S). These results support earlier assignments based on semiempirical and ab initio studies on a thermal decomposition product of rubroflavin. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 265–270, 2003
Systemic, but not local, administration of cannabinoid CB1 receptor agonists modulate prefrontal cortical acetylcholine efflux in the rat
Authors: Verrico Christopher D. , Jentsch J. David , Dazzi Laura , Roth Robert H.
Published: April 2003

Drugs acting on brain cannabinoid CB1 receptors exert complex actions on modulatory transmitters that are involved in attention and cognition; however, little is known about the precise pharmacological and anatomical mechanisms that govern these effects. Previously demonstrated effects of cannabinoids on acetylcholine (ACh) in the hippocampus prompted us to evaluate changes in the prefrontal cortex, a site associated with mnemonic and attentional functions. We utilized in vivo microdialysis, coupled with direct reverse perfusion of agents, to study the actions on cannabinoidergic drugs on ACh release within the rat frontal cortex. Systemic administration of the CB1 receptor agonists Δ9‐tetrahydrocannabinol (THC) or WIN 55,212‐2 (WIN) dose‐ and time‐dependently increased ACh release; these effects were blocked by pretreatment with the selective CB1 receptor antagonist / partial inverse agonist SR141716A (SR). THC applied by reverse dialysis in the frontal cortex caused no change in ACh release, although intrastriatal infusions of THC decreased ACh efflux. These data indicate that cannabinoid agonists potentiate ACh release in the frontal cortex by activating cannabinoid receptors in brain regions other than the frontal cortex. Synapse 48:178–183, 2003. © 2003 Wiley‐Liss, Inc.
The difficulty in distinguishing product from process
Authors: Abadi Christiano Danny , Bahill Terry
Published: April 2003

When engineers design a system, they must design both the product and the process that will create it. Accordingly, systems engineers must write requirements for the product and the process. Stating these requirements in separate documents might make it easier to get the requirements right and manage the requirements when either the product or the process requirements change. But, of course, these two sets of documents must be intricately interrelated, integrated, and produced with extensive feedback loops. This paper shows the results of an experiment that was designed to investigate the difficulty in distinguishing between the product and the process. © 2003 Wiley Periodicals, Inc. Syst Eng 6: 106–115, 2003 DOI 10.1002/sys.10035
The synthesis of optimal systems design solutions
Authors: Shell Tony
Published: April 2003

By building on earlier established work, a nonrecursive approach to design optimization is proposed. A “fractal” method of design is developed that embraces the entire space of candidate system solutions. It provides for the direct synthesis of optimal system design solutions of complex system implementations with multiple components, embodying different technologies, and with multiple levels of design hierarchy. The derivation and decomposition of comparative evaluation criteria and tradeoff functions, using “mathematical orders” over the space of candidate systems, is explored in detail. An extended form of the Subsystem Tradeoff Functional Equation (i.e., nk‐STFE for n components and k evaluation criteria) is developed, and its application to optimal design of complex systems architectures is presented. In particular, the effect of overall constraints on system implementation—in terms of combinatorial constraints on component choice, and the manner in which this is incorporated into a systems‐theoretic approach to complex system design—is discussed. The development of formal (systems‐theoretic) constructs, theorems, and theorem proofs, are provided where necessary. © 2003 Wiley Periodicals, Inc. Syst Eng 6: 92–105, 2003
Human T‐cell leukemia virus type 1 Tax protein stimulates the interferon‐responsive enhancer element via NF‐κB activity1
Authors: Shimizu Toshiki , Kawakita Shigenari , Li Qin-Hua , Fukuhara Shirou , Fujisawa Jun-ichi
Published: April 2003

Gene expression in Rat‐1 fibroblast cells transformed by Tax from human T‐cell leukemia virus type 1 was studied using the reverse transcriptase polymerase chain reaction differential display technique. The analysis revealed eight genes that were upregulated and one gene that was suppressed in Tax‐transformed cells. Interestingly, at least four of the upregulated genes were interferon‐stimulated genes. Promoter analysis of the 2′,5′‐oligoadenylate synthetase gene, which was activated in both Tax‐transformed Rat‐1 cells and primary adult T‐cell leukemia cells, demonstrated that Tax indirectly activates its interferon‐responsive enhancer element in a nuclear factor‐κB pathway‐dependent manner, indicating a close association of interferon signaling with the transformation by Tax.
The clinical use of milnacipran for depression
Authors: Morishita Shigeru , Arita Seizaburo
Published: April 2003

We examined the relation between dosage and efficacy, and the predictors of response to milnacipran. There was no difference between 50 and 100 mg dose. However, the 100 mg dose had a faster onset of action than the 50 mg dose. An age and an episode have been predictors of milnacipran.
Door to Needle Times Bulls' Eye or Just Bull? The Effect of Reducing Door to Needle Times on the Appropriate Administration of Thrombolysis: Implications and Recommendations
Authors: Clare Carl , Bullock Ian
Published: April 2003

The provision of thrombolysis in a timely fashion is the mainstay of treatment for acute myocardial infarction. With the publication of the National Service Framework (NSF) for Coronary Heart Disease increasing efforts have been put into the reduction of the ‘pain to needle time’. Of the various parts of the patient journey the time delays in hospital are the easiest to resolve. Published research shows that the time taken for the patient to call for help is intractable at present. Therefore, the obvious target for the reduction in the overall time from pain to treatment is the in hospital portion of the delay (the door to needle time). There are several methods that have been recommended for the reduction of the door to needle time. However, the increasing focus on the door to needle time is leading health care providers away from other issues such as the safety and accuracy of assessment by a non-cardiologist. Furthermore, the standards for audit of the door to needle time have not been set by the NSF and this has led to the presentation of selected data and the avoidance of discussing issues of accuracy and appropriateness.