bluuebunny/crossref_metadata_2025 huggingface dataset:
I–‐Catalyzed Reaction of 5‐Methoxyoxazoles with Organic Iodides – An Efficient Synthesis of Azalactones
Authors: Lu Lianghua , Lu Ping , Ma Shengming
Published: November 2006

An I–‐catalyzed methoxy carbon–oxygen bond cleavage in 5‐methoxyoxazoles leading to the synthesis of azalactones, precursors of quaternary amino acids, has been developed. A series of 4‐substituted azalactones were obtained through the variation of the alkyl iodides and differently substituted 5‐methoxyoxazoles. Further study indicated that azalactone 3aa may be easily converted to benzoyl‐protected quaternary amino acid 4aa. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Synthesis of a Cyclic Tetrameric Purine by Successive Cross‐Coupling Reactions and Subsequent Pd‐Catalyzed Cyclization
Authors: Guthmann Holger , Könemann Martin , Bach Thorsten
Published: November 2006

The tetrameric N‐benzyl‐protected purine (quaterpurine) 2 was synthesized and characterized as its palladium complex [2·Pd]. The synthesis commenced with the Pd‐catalyzed cross‐coupling of 8‐zincated 9‐benzyl‐6‐chloro‐8‐iodopurine (9) and 9‐benzyl‐6‐iodopurine (11) establishing the first C‐6/C‐8 bond. The sequence was repeated twice after iodo‐de‐chlorination at C‐6′ (C‐6″) of the respective dimer 12 and trimer 15. The final ring closure was achieved at the tetrameric 6″′‐chloro‐8‐iodoquaterpurine 3b by a reductive intramolecular cross‐coupling with hexamethylditin in the presence of Pd2(dba)3 and P(2‐furyl)3. The overall yield in the eight step sequence was 17 % starting from 9‐benzyl‐6‐chloropurine (8), the immediate precursor of 11. Other strategies to combine the purine fragments, i.e. by dimer/dimer bond formation or by regioselective cross‐coupling, were not successful. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
A New Synthetic Route for the Preparation of 1,10‐Phenanthroline Derivatives
Authors: Moudam Omar , Ajamaa Fettah , Ekouaga Allan , Mamlouk Hind , Hahn Uwe , Holler Michel , Welter Richard , Nierengarten Jean‐François
Published: November 2006

The intermediate resulting from the addition of an organolithium reagent to 1,10‐phenanthroline has been quenched with benzyl bromide. The resulting protected dihydrophenanthroline intermediate is thus stabilized and can be used for further chemical transformations. This strategy allows to modify the reactivity of the phenanthroline backbone and offers a unique opportunity to perform chemical modifications that would not be possible when starting from 1,10‐phenanthroline. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
Who is this Donald? How social categorization affects aggression‐priming effects
Authors: Otten Sabine , Stapel Diederik A.
Published: November 2006

When investigating the effects of aggression on person perception, many studies have relied on the famous ‘Donald’ paradigm (e.g., Srull & Wyer, 1979). Little attention has been paid, however, to the role that is played by the social identity of Donald (the target of perception) in such effects. Three studies with Dutch participants, consistently reveal that judgments of an ingroup (Dutch) target are less prone to be affected by aggression priming than judgments of an outgroup (Moroccan, Surinamese, German) target, and that this effect is moderated by the extent to which the target's group is associated with aggressiveness. Importantly, the studies show that such association can be created not only via well‐established stereotypes (e.g., ‘Moroccans are aggressive’), but also via subtle contextual priming. When priming activates an association between ingroup and aggressiveness (‘The Dutch are aggressive’), the subsequent evaluation of the ingroup targets can also be influenced negatively. The present research thus demonstrates that social categorizations and the contextual associations attached to them delineate an important boundary condition for aggression priming effects. Copyright © 2006 John Wiley & Sons, Ltd.
LIF detection of peptides and proteins in CE
Authors: García‐Campaña Ana M. , Taverna Myriam , Fabre Huguette
Published: November 2006

CE‐ and microchip‐based separations coupled with LIF are powerful tools for the separation, detection and determination of biomolecules. CE with certain configurations has the potential to detect a small number of molecules or even a single molecule, thanks to the high spatial coherence of the laser source which permits the excitation of very small sample volumes with high efficiency. This review article discusses the use of LIF detection for the analysis of peptides and proteins in CE. The most common laser sources, basic instrumentation, derivatization modes and set‐ups are briefly presented and special attention is paid to the different fluorogenic agents used for pre‐, on‐ and postcapillary derivatization of the functional groups of these compounds. A table summarizing major applications of these derivatization reactions to the analysis of peptides and proteins in CE‐LIF and a bibliography with 184 references are provided which covers papers published to the end of 2005.
Universal method for synthesis of artificial gel antibodies by the imprinting approach combined with a unique electrophoresis technique for detection of minute structural differences of proteins, viruses, and cells (bacteria). III: Gel antibodies against cells (bacteria)
Authors: Bacskay Ivett , Takátsy Anikó , Végvári Ákos , Elfwing Anders , Ballagi‐Pordány András , Kilár Ferenc , Hjertén Stellan
Published: November 2006

Artificial antibodies in the form of gel granules were synthesized from the monomers acrylamide and N,N'‐methylenebisacrylamide by the imprinting method in the presence of Echerichia coli bacteria as template. The electrophoretic migration velocities of the gel antibodies (i) saturated with the antigen (Escherichia coli MRE‐600), (ii) freed of the antigen, and (iii) resaturated with bacteria, were determinated by electrophoresis in a rotating narrow‐bore tube of 245 mm length and the 2.5 and 9.6 mm inner and outer diameters, respectively. Removal of bacteria from the gel antibodies was made by treatment with enzymes, followed by washing with SDS and buffer. Gel granules becoming charged by adsorption of bacteria move in an electrical field. We obtained a significant selectivity of gel antibodies for E. coli MRE‐600, since the granules did not interact with Lactococcus lactis; and when E. coli BL21 bacteria were added to the gels selective for E. coli MRE‐600, a significant difference in the migration rate of the complexes formed with the two strains was observed indicating the ability of differentiation between the two strains. The gel antibodies can be used repeatedly. The new imprinting method for the synthesis of artificial gel antibodies against bioparticles described herein, and the classical electrophoretic analysis technique employed, thus represent – when combined – a new approach to distinguish between different types and strains of bacteria. The application area can certainly be extended to cover other classes of cells.
Analysis of selected constituents in methanolic extracts of Hypericum perforatum collected in different localities by capillary ITP‐CZE
Authors: Hamoudová Rafífa , Pospíšilová Marie , Spilková Jiřina
Published: November 2006

The on‐line combination of CZE with capillary ITP (ITP‐CZE) was used for the separation and quantification of selected flavonoids and phenolic acids in Hypericum perforatum leaves and flowers collected in six different localities in Slovakia. The leading electrolyte in the ITP preseparation step was 10 mM HCl with Tris as counterion (pH* 7.2). The terminating electrolyte was 50 mM boric acid of pH* 8.2 (adjusted with barium hydroxide). The BGE in the electrophoretic step contained 25 mM β‐hydroxy‐4‐morpholinopropanesulfonic acid (MOPSO), 50 mM Tris, 65 mM boric acid, pH* 8.3. The content of methanol in all electrolytes was 20% v/v. The total time of the analysis (including the preseparation step) was ∼35 min. The rectilinear calibration ranges were between 0.125 and 5.0 µg/mL with kaempferol as internal standard. The correlation coefficients ranged between 0.9912 (for quercitrin and chlorogenic acid) and 0.9988 (for isoquercitrin). The RSD values are between 0.86 and 7.78% (n = 6) when determining rutin and quercetin (4 µg/mL). The optimized method was employed for the assay of flavonoids in medicinal plant extract of different collections of Hypericum perforatum haulm. The variability of the content of the active components depending on the place of collection was confirmed.
CE for cytokinin analyses: A review
Authors: Ge Liya , Tan Shirley , Yong Jean Wan Hong , Tan Swee Ngin
Published: November 2006

Analyses of cytokinins are very important in both plant physiological and biomedical research as they are implicated in many biological processes. Reliable, sensitive, selective and inexpensive methods that are flexible and designed for automation are required for these analyses. This review addresses the advances made in the separation and determination of cytokinins by CE as well as the other applications of CE (i.e., determination of dissociation constants and complexation constants of cytokinins). The various CE modes used to separate the compounds and the quantification strategies are examined. Special attention is also focused on those aspects that improve on the sensitivity and/or selectivity, such as sample extraction and preconcentration, on‐line preconcentration techniques (stacking), and/or specific detectors (e.g., MS). With the coupling to the preconcentration techniques and certain detection systems, numerous CE methods can potentially be adapted for the analysis of cytokinins in complex biological samples. Therefore, we would anticipate wider applications of CE methods in the near future for cytokinin analyses, which should facilitate a decrease in analysis cost and should help to improve analysis efficiency.
Optimization of CZE for analysis of phytochemical bioactive compounds
Authors: Li Peng , Li Shao Ping , Wang Yi Tao
Published: November 2006

Advantages of CZE such as high efficiency, low cost, short analysis time, and easy implementation result in its wide applications for analysis of phytochemical bioactive compounds (e.g. flavonoids, alkaloids, terpenoids, phenolic acid, saponins, anthraquinones and coumarins). However, several aspects, including sample preparation, separation, and detection have significant effects on CZE analysis. Therefore, optimization of these procedures is necessary for development of the method. In this review, sample preparation such as extraction method and preconcentration, separation factors including buffer type, concentration and pH, additives, voltage and temperature, as well as detection, e.g. direct and indirect UV detection, LIF and MS were discussed for optimization of CZE analysis on phytochemical bioactive compounds. The optimized strategies were also reviewed.
Facile separation and determination of Aconitine alkaloids in traditional Chinese medicines by CE with tris(2,2'‐bipyridyl) ruthenium(II)‐based electrochemiluminescence detection
Authors: Yin Jianyuan , Guo Weiwei , Du Yan , Wang Erkang
Published: November 2006

A facile CE method coupled with tris(2,2'‐bipyridyl) ruthenium(II)‐based electrochemiluminescence [Ru(bpy)32+] detection was developed for simultaneous determination of Aconitum alkaloids, i.e., hypaconitine (HA), aconitine (AC), and mesaconitine (MA) in baseline separation. The optimal separation of these Aconitum alkaloids was achieved in a fused‐silica capillary column (50 cm×25 µm id) with 30 mM phosphate solution (pH 8.40) as running buffer at 12 kV applied voltage. The three alkaloids can be determined within 10 min by a single run. The calibration curves showed a linear range from 2.0×10−7 to 2.0×10−5 M for HA, 3.4×10−7 to 1.7×10−5 M for AC, and 3.8×10−7 to 1.9×10−5 M for MA. The RSDs for all analytes were below 3.01%. Good linear relationships were found with correlation coefficients for all analytes exceeding 0.993. The detection limits were 2.0×10−8 M for HA, 1.7×10−7 M for AC, and 1.9×10−7 M for MA under optimal conditions. This method was successfully applied to determine the three alkaloids in Aconitum plants.
ITP in dynamically double‐coated fused‐silica capillaries
Authors: Caslavska Jitka , Thormann Wolfgang
Published: November 2006

Bidirectional ITP in fused‐silica capillaries double‐coated with Polybrene and poly‐(vinylsulfonate) is a robust approach for analysis of low‐molecular‐mass compounds. EOF towards the cathode is strong (mobility >4.0×10−8 m2/Vs) within the entire pH range investigated (2.40–8.08), dependent on ionic strength and buffer used and, at constant ionic strength, higher at alkaline pH. Electrokinetic separations and transport in such coated capillaries can be described with a dynamic computer model which permits the combined simulation of electrophoresis and electroosmosis in which the EOF is predicted either with a constant (i.e. pH‐ and ionic strength‐independent) or a pH‐ and ionic strength‐dependent electroosmotic mobility. Detector profiles predicted by computer simulation agree qualitatively well with bidirectional isotachopherograms that are monitored with a setup comprising two axial contactless conductivity detectors and a UV absorbance detector. The varying EOF predicted with a pH‐ and ionic strength‐dependent electroosmotic mobility can be regarded as being realistic.
Chiral resolution of tryptophan derivatives by CE using canine serum albumin and bovine serum albumin as chiral selectors
Authors: Hödl Heike , Koidl Julia , Schmid Martin G. , Gübitz Gerald
Published: November 2006

This work deals with the application of BSA and canine serum albumin (CSA) for enantioseparation of tryptophan derivatives with CE. The aim of this work was the investigation of the influence of different functional groups of tryptophan derivatives on enantioseparation. CSA as a chiral selector was tested to compare its selector properties with those of BSA. The enantiomers of the tryptophan derivatives were separated by adding BSA or CSA to the BGE. The influence of pH, temperature, BSA and CSA concentration and organic modifiers was investigated. It was found that the stereoselectivity for the different tryptophan derivatives is dependent on the albumin species. It turned out that the different functional groups of the derivatives showed a significant influence on stereoselectivity.
MEKC: An update focusing on practical aspects
Authors: Silva Manuel
Published: November 2006

This paper reviews recent methodological and instrumental advances in MEKC. Improvements in sensitivity arising from the use of on‐line sample concentration (sweeping, stacking, and combination of both protocols) and derivatization (in‐capillary reactions and coupling with flow‐injection systems) and improvements in resolution obtained by changing the composition of the BGE (e.g., with organic modifiers, ionic liquids, nonionic and zwitterionic surfactants, mixed micelles, and vesicles) or using coated capillaries are discussed in detail. In addition, MS and LIF spectroscopy are examined in relation to their advantages and restrictions as applied to MEKC analysis. Some thoughts on potential future directions are also expressed.
Celebrating the 65th birthday of Professor Petr Boček
Authors: Křivánková Ludmila
Published: November 2006

No abstracts.
Clinically significant non‐major depression in a community‐dwelling elderly population: epidemiological findings
Authors: Chen Cheng‐Sheng , Chong Mian‐Yoon , Tsang Hin‐Yeung
Published: November 2006

Objective

The aim of this study was to investigate the 1‐month prevalence, symptom profiles and demographic correlates in late‐life clinically significant non‐major depression (CSNMD) among a community‐dwelling elderly population.

Methods

One thousand five hundred subjects aged 65 years and older, who were randomly selected from three communities in Taiwan, received comprehensive psychiatric assessment by trained psychiatrists. Two categorical diagnoses of depressive disorder, including major depression and CSNMD, were made. The 1‐month prevalence was calculated. Frequencies of depressive symptoms across CSNMD and major depression were compared. The risks of CSNMD based on demographic characteristics were estimated using multinominal logistic regression.

Results

The 1‐month prevalence of CSNMD among the community‐dwelling elderly was 8.8%. Symptoms of diminished interest, appetite changes, sleep disturbance, worthlessness or inappropriate guilt, trouble in concentrating or indecisiveness, and suicidal thoughts or acts were less frequent in CSNMD than in major depression, but symptoms of depressed mood, psychomotor changes, and fatigue or loss of energy were as frequent in both categories of illness. CSNMD shares similar demographic risks, such as living in an urban area, female gender and low educational status, with major depression.

Conclusions

CSNMD is common among community‐dwelling elders in Taiwan, and with its identical demographic characteristics, but qualitatively different presentation, we suggest CSNMD may be considered part of a spectrum of severe late life depressions with a distinct manifestation. Major depression and CSNMD may share common demographic characteristics with different manifestation. We conclude that late‐life depression is a dimensional disease. Copyright © 2006 John Wiley & Sons, Ltd.
The rate of conversion of mild cognitive impairment to dementia: predictive role of depression
Authors: Gabryelewicz T. , Styczynska M. , Luczywek E. , Barczak A. , Pfeffer A. , Androsiuk W. , Chodakowska‐Zebrowska M. , Wasiak B. , Peplonska B. , Barcikowska M.
Published: November 2006

Background

Mild cognitive impairment (MCI) is a condition referring to the persons with cognitive deficits measurable in some form or another, but not meeting criteria for dementia, and who have an increased risk of becoming demented.

Objective

To establish the rate of progression to dementia in MCI, to investigate the risk of conversion for amnestic vs multiple‐domains subtypes, and to identify the predictors of progression.

Methods

MCI (n = 105) individuals enrolled in a longitudinal study received annual clinical and psychometric examinations for up to a mean of 3 years. The diagnosis of MCI according to Mayo Clinic Petersen's Criteria was conducted by a panel of specialists.

Results

After 3 years of follow‐up, 23 of 105 subjects with MCI were diagnosed with dementia. 40 showed cognitive decline not dementia, 34 were stable and showed no cognitive decline or improvement, while eight showed cognitive improvement.

Conclusions

We conclude that conversion rate from MCI to DSM‐IIIR dementia was 21.9% over a period of 3 years. The occurrence of depressive symptoms may constitute a predictor for those who are more likely to progress to dementia. The risk of conversion to dementia was higher among the subjects with an evidence of impairment extending beyond memory than with those who suffered only from memory deficits, and the subjects who converted to dementia in this subtype had significantly higher baseline plasma total homocysteine levels than non‐converters. Copyright © 2006 John Wiley & Sons, Ltd.
Evaluating the outcome of interventions on quality of life in dementia: selection of the appropriate scale
Authors: Schölzel‐Dorenbos Carla J. M. , Ettema Teake P. , Bos Joke , Boelens‐van der Knoop Ellen , Gerritsen Debby L. , Hoogeveen Frans , de Lange Jacomine , Meihuizen Lucinda , Dröes Rose‐Marie
Published: November 2006

Background

A literature study was conducted to contribute to an adequate use of quality of life (QoL) instruments for the evaluation of interventions in dementia care by providing an overview of properties of QoL measures that acknowledge domains important to dementia patients.

Methods

Domains important to patients, and domains that professional caregivers in different settings focus on, are compared to domains represented in nine QoL instruments. Data on psychometrics and applicability are generated.

Results

Four instruments best represent domains of QoL important to patients and domains professional caregivers in 24‐h care and daytime activities focus on. Two are self‐rating instruments: Schedule for the Evaluation of Individual Quality of Life, applicable in mild dementia, measuring individual QoL of patient and informal caregiver, and Quality of Life‐Alzheimer's Disease Scale, which can be applied up to moderately severe dementia. For patients with advanced dementia receiving residential care, the observational instruments Qualidem and Discomfort scale‐Dementia of Alzheimer Type are recommended. The first is easily administered by nurse assistants or occupational therapists and covers several QoL domains on which they focus in daily practice. The second can be used by various professionals.

Conclusions

QoL assessment provides a format for patients and (in)formal caregivers to express whether an intervention has made an important difference to the patient's life. Improvement of QoL in dementia should have high priority in care, treatment and research. This study shows that severity of dementia, care type, setting, and the specific QoL domains an intervention focuses on, determine which QoL instrument is most appropriate in a specific situation. Copyright © 2006 John Wiley & Sons, Ltd.
Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia
Authors: Zuidema Sytse U. , Derksen Els , Verhey Frans R.J. , Koopmans Raymond T.C.M.
Published: November 2006

Objective

To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes.

Methods

Cross‐sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational nurses during regular care‐giving in a 2‐week observational period prior to assessment. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory‐ Nursing home version (NPI‐NH; frequency X severity score ≥ 4) and the Cohen‐Mansfield Agitation Inventory (CMAI; symptoms occurring at least once a week).

Results

More than 80% of these patients suffered from at least one clinically significant symptom, as defined with the NPI‐NH frequency X severity score ≥ 4. Measured with the NPH‐NH agitation/aggression, apathy and irritability were the most frequently observed behaviors, with prevalences of 30–35%. Using the CMAI, 85% of the patients showed at least one symptom of agitation, of which general restlessness was observed most frequently (44%). Other frequently observed symptoms with prevalence rates of 30% were cursing or verbal aggression, constant request for attention, negativism, repetitious sentences, mannerisms, pacing, and complaining. Physically aggressive symptoms such as hitting, kicking, biting occurred less often (less than 13%).

Conclusions

Prevalence rates of neuropsychiatric symptoms in Dutch nursing home patients with dementia residing in SCUs are high, especially agitation and apathy. Insight into the prevalence rates of individual symptoms in patients with dementia has important practical consequences for the accurate planning of staff allotment and stresses the need for patient oriented care. Copyright © 2006 John Wiley & Sons, Ltd.
Health utilities in mild cognitive impairment and dementia: a population study in Sweden
Authors: Ekman Mattias , Berg Jenny , Wimo Anders , Jönsson Linus , McBurney Christopher
Published: November 2006

Objective

To collect new primary data on community‐based health utilities (time trade‐off values) in different stages of mild cognitive impairment and dementia from a general population sample.

Methods

A cross‐sectional study including 1,800 randomly selected members of the Swedish public aged 45–84 was performed through a postal survey; 42% response rate. The Clinical Dementia Rating scale was used for describing progressive stages of dementia in vignettes that were used in combination with time trade‐off questions for valuing the perceived quality of life in these stages.

Results

The time‐trade off values varied considerably across the progressive disease stages. The mean score was 0.82 for mild cognitive impairment, 0.62 for mild dementia, 0.40 for moderate dementia, and 0.25 for severe dementia. In multiple regression analyses, the scores were relatively insensitive to demographic factors like age, gender and self‐assessed health.

Conclusions

The results showed that the average time trade‐off values declined sharply from mild cognitive impairment to progressing stages of dementia. Since there are many methodological challenges involved in measuring health state utilities in mild cognitive impairment and dementia, more research that evaluates different methods would be welcome. Copyright © 2006 John Wiley & Sons, Ltd.
Stronger symptoms of depression predict high coronary heart disease mortality in older men and women
Authors: Ahto Merja , Isoaho Raimo , Puolijoki Hannu , Vahlberg Tero , Kivelä Sirkka‐Liisa
Published: November 2006

Background

Most cohort studies have found depressive symptoms to be associated with increased cardiovascular mortality in the elderly, but follow‐up times have often been short and study populations small.

Objectives

To describe associations between stronger symptoms of depression and the risk of death from coronary heart disease (CHD) or myocardial infarction (MI) in elderly Finnish subjects free of CHD at the baseline.

Methods

This study is a prospective population‐based epidemiological and clinical twelve‐year follow‐up study in Lieto Health Centre, Finland. The basic population consisted of 1196 elderly (64 years of age or older) persons who lived in the municipality of Lieto in southwestern Finland in 1990. The occurrence of CHD was determined on the basis of electrocardiographic (ECG) findings, Rose questionnaire and the diagnoses in medical records. The persons with CHD were excluded from the study population. Symptoms of depression at the baseline were measured with the Zung Self‐rating Depression Scale (ZSDS). Mortality was followed up for about 12 years.

Results

The Kaplan‐Meier survival curves showed stronger symptoms of depression to be related to high risks of mortality from CHD or MI among men and women. According to the Cox model for men significant predictors for higher risk of CHD or MI mortality were stronger symptoms of depression, higher age and a large number of medications in use. When women were examined, significant predictors were stronger symptoms of depression and a large number of medications in use.

Conclusions

Stronger symptoms of depression are an independent risk factor for high CHD or MI mortality in aged Finnish men and women free of CHD at baseline. Copyright © 2006 John Wiley & Sons, Ltd.
Doxycycline induces caspase‐dependent apoptosis in human pancreatic cancer cells
Authors: Mouratidis Petros X.E. , Colston Kay W. , Dalgleish Angus G.
Published: November 2006

Doxycycline (DC) belongs to the tetracycline family of antibiotics and has been used clinically for over 5 decades. Despite advances in understanding the molecular pathogenesis of pancreatic cancer, no chemotherapy course has shown significant effectiveness. Hence new treatments are needed. In this study we report the pro‐apoptotic effects of DC in 2 pancreatic adenocarcinoma cell lines, T3M4 and GER. Cell proliferation was measured using the SRB protein dye. Induction of apoptosis was detected using ELISA. Caspase activation was detected using either immunoblotting or a colorimetric assay based on cleavage of caspase‐associated substrates. Expression of proteins and post‐translational modifications were determined using immunoblotting. Treatment of pancreatic cancer cells with DC reduces their proliferation. This reduction is, at least partly, due to increased caspase‐dependent apoptosis involving activation of caspase3, caspase7, caspase8, caspase9, caspase10 and increased levels of FADD. Inhibition of caspase8 or caspase10 but not caspase9 significantly decreases DC‐induced apoptosis in both cell lines. Furthermore treatment of pancreatic cancer cells with DC increases protein levels of Bax and phosphorylation of members of the p38MAPK pathway such as p38MAPK, MKK3/6 and MAPKAPK2. These results provide an insight into mechanisms behind the pro‐apoptotic effects of DC in pancreatic cancer cells. © 2006 Wiley‐Liss, Inc.
The effects of aging on tumor growth and angiogenesis are tumor‐cell dependent
Authors: Reed May J. , Karres Nathan , Eyman Daniel , Cruz Abigail , Brekken Rolf A. , Plymate Stephen
Published: November 2006

It is generally accepted that histologically similar tumors grow more slowly, with less angiogenesis, in aged mice relative to young mice. We subcutaneously implanted TRAMP‐C2 tumor cells, a prostate cancer cell line not previously examined in aging, into syngeneic C57/Bl6 young (4 month) and aged (20 month) mice and compared tumor growth and angiogenesis. Unexpectedly, the prostate tumors grew as fast in aged as in young mice. Angiogenesis in TRAMP‐C2 tumors was robust, with no differences between the young and aged mice in the number of vessels, distribution of vessel sizes or features of vessel maturation. Aged mice had lower levels of serum testosterone than the young mice. VEGF levels were similar in the tumors and sera of the young and aged mice. Comparison with B16/F10 melanoma, a cancer cell line that is representative of previous studies in aged mice, showed that B16/F10 tumors grew minimally in the aged mice. In contrast to the B16/F10, TRAMP‐C2 tumors had an extracellular matrix with significantly higher levels of MMP2 and MMP9 expression and activity. These unique results demonstrate that tumor progression can be as robust in aged tissues as young tissues. The ability of aged mice to grow large, vascularized prostate tumors is associated with high levels of MMP2/9 activity that may produce a permissive environment for tumor growth and angiogenesis. These data demonstrate that tumor‐cell specific features determine the effect of aging on tumor growth and angiogenesis. © 2006 Wiley‐Liss, Inc.
Involvement of ribonucleotide reductase M1 subunit overexpression in gemcitabine resistance of human pancreatic cancer
Authors: Nakahira Shin , Nakamori Shoji , Tsujie Masanori , Takahashi Yuji , Okami Jiro , Yoshioka Shinichi , Yamasaki Makoto , Marubashi Shigeru , Takemasa Ichiro , Miyamoto Atsushi , Takeda Yutaka , Nagano Hiroaki , Dono Keizo , Umeshita Koji , Sakon Masato , Monden Morito
Published: November 2006

Pancreatic cancer is the most lethal of all solid tumors partially because of its chemoresistance. Although gemcitabine is widely used as a first selected agent for the treatment of this disease despite low response rate, molecular mechanisms of gemcitabine resistance in pancreatic cancer still remain obscure. The aim of this study is to elucidate the mechanisms of gemcitabine resistance. The 81‐fold gemcitabine resistant variant MiaPaCa2‐RG was selected from pancreatic cancer cell line MiaPaCa2. By microarray analysis between MiaPaCa2 and MiaPaCa2‐RG, 43 genes (0.04%) were altered expression of more than 2‐fold. The most upregulated gene in MiaPaCa2‐RG was ribonucleotide reductase M1 subunit (RRM1) with 4.5‐fold up‐regulation. Transfection with RRM1‐specific RNAi suppressed more than 90% of RRM1 mRNA and protein expression. After RRM1‐specific RNAi transfection, gemcitabine chemoresistance of MiaPaCa2‐RG was reduced to the same level of MiaPaCa2. The 18 recurrent pancreatic cancer patients treated by gemcitabine were divided into 2 groups by RRM1 levels. There was a significant association between gemcitabine response and RRM1 expression (p = 0.018). Patients with high RRM1 levels had poor survival after gemcitabine treatment than those with low RRM1 levels (p = 0.016). RRM1 should be a key molecule in gemcitabine resistance in human pancreatic cancer through both in vitro and clinical models. RRM1 may have the potential as predictor and modulator of gemcitabine treatment. © 2006 Wiley‐Liss, Inc.
Imatinib mesylate potentiates topotecan antitumor activity in rhabdomyosarcoma preclinical models
Authors: McDowell Heather P. , Meco Daniela , Riccardi Anna , Tanno Barbara , Berardi Anna C. , Raschellà Giuseppe , Riccardi Riccardo , Dominici Carlo
Published: November 2006

High levels of PDGFR expression in primary rhabdomyosarcoma (RMS) have been associated with disease progression. To date however, there are no reports on the activity of imatinib mesylate, a selective PDGFR inhibitor, in RMS preclinical models. A panel of 5 RMS cell lines was used to investigate the expression of PDGFRα and PDGFRβ, c‐Kit and the multidrug transporter ABCG2 (also inhibited by imatinib). In vitro and in vivo experiments were performed using RD (embryonal) and RH30 (alveolar) cell lines to determine the efficacy of imatinib as single agent and in combination with topotecan (TPT). PDGFRβ was significantly expressed in all cell lines, with the highest levels in RD, while PDGFR α and ABCG2 were significantly expressed only in RH30 and RMZ‐RC2. c‐Kit was not detected. PDGFRβ signaling was active in RD but not in RH30, whilst PDGFRα signaling was not active in either cell lines. Significant ABCG2‐mediated extrusion of Hoechst 33342 was demonstrated in RH30 but not in RD, and was inhibited by imatinib and the specific ABCG2 inhibitor Ko143. In vitro, imatinib was not active as a single agent at therapeutic concentrations, but significantly potentiated TPT antitumor activity in both cell lines. In vivo experiments using tumor xenografts confirmed the synergistic interaction in both cell lines. These results suggest that at least 2 different mechanisms—inhibition of ABCG2 and/or PDGFRβ—are involved in the synergistic interaction between imatinib and TPT, and support the use of this combination for the treatment of high‐risk RMS patients. © 2006 Wiley‐Liss, Inc.
The 6‐maleimidocaproyl hydrazone derivative of doxorubicin (DOXO‐EMCH) is superior to free doxorubicin with respect to cardiotoxicity and mitochondrial damage
Authors: Lebrecht Dirk , Geist Andrea , Ketelsen Uwe‐Peter , Haberstroh Jörg , Setzer Bernhard , Kratz Felix , Walker Ulrich A.
Published: November 2006

Doxorubicin causes a chronic cardiomyopathy in which genetic and functional lesions of mitochondria accumulate in the long‐term and explain in part the delayed onset of heart dysfunction. DOXO‐EMCH a 6‐maleimidocaproyl hydrazone derivative of doxorubicin, is an albumin binding prodrug which has entered clinical trials because of its superior antitumor and toxicological profile. In the present work, we examined the chronic cardiotoxicity of DOXO‐EMCH in direct comparison with doxorubicin. Rats (11 weeks of age) were treated with intravenous doxorubicin (0.8 mg/kg weekly for 7 weeks), an equimolar dose of DOXO‐EMCH (1.1 mg/kg), or with 3.3 mg/kg of DOXO‐EMCH. Controls received saline. Animals were euthanized at 48th week. Rats exposed to doxorubicin had a severe clinical, and histopathological cardiomyopathy with depressed myocardial activity of cytochrome c‐oxidase (COX, 26% of controls), reduced expression of the mtDNA‐encoded COX II subunit, decreased mtDNA copy numbers (46% of controls), and high levels of malondialdehyde and superoxide (787% of controls). All parameters were highly correlated with myocardial damage. Both DOXO‐EMCH groups did not differ from controls with regard to clinical symptomatology, mortality and mitochondrial enzymes, although the myocardia of the high‐dose group had slightly increased histopathological abnormalities, depressed mtDNA copies (74% of controls) and elevated superoxide levels (347% of controls). Doxorubicin‐exposed hearts and to a lesser extent the myocardia of both DOXO‐EMCH groups contained mtDNA‐deletions. In summary both DOXO‐EMCH doses were superior over doxorubicin with respect to clinical and histopathological evidence of cardiomyopathy, myocardial COX‐activity, COX II expression, mtDNA‐content, mtDNA mutation loads and superoxide production in rats. © 2006 Wiley‐Liss, Inc.
Polymorphisms in the genes ERCC2, XRCC3 and CD3EAP influence treatment outcome in multiple myeloma patients undergoing autologous bone marrow transplantation
Authors: Vangsted Annette , Gimsing Peter , Klausen Tobias W. , Nexø Bjørn A. , Wallin Håkan , Andersen Pernille , Hokland Peter , Lillevang Søren T. , Vogel Ulla
Published: November 2006

Individual variations in the ability to cope with DNA damage by DNA repair may be essential for the response to chemotherapy, since cancer cells from patients with an effective DNA repair may survive treatment. We have studied the effect on time to treatment failure (TTF) and overall survival (OS) of polymorphism in the DNA repair genes ERCC1, ERCC2 and XRCC3, and in the apoptotic genes PPP1R13L and CD3EAP in 348 patients with multiple myeloma undergoing autologous bone marrow transplantation. Carriers of the variant C‐allele of ERCC2 K751Q, the variant T‐allele of XRCC3 T241M and the variant A‐allele of CD3EAP G‐21A had a 1.3‐fold, 1.8‐fold and 1.9‐fold longer TTF, respectively, than homozygous wild type carriers (p = 0.006, p = 0.004, p < 0.001). The polymorphism CD3EAP G‐21A also had significant effect on OS (p < 0.045). The polymorphism ERCC2 K751Q may to be related to sex, since the prolonged TTF was only seen in women (p = 0.001). Carriers of the combination of variant alleles of ERCC2 K751Q and XRCC3 T241M had 2.8‐fold longer TTF (p = 0.0002). This indicates that suboptimal repair of both DNA mechanisms favors prolonged TTF and that polymorphism in ERCC2, XRCC3 and CD3EAP predicts the outcome for patients treated with autologous stem cell transplantation. © 2006 Wiley‐Liss, Inc.
Emmprin in epithelioid sarcoma: Expression in tumor cell membrane and stimulation of MMP‐2 production in tumor‐associated fibroblasts
Authors: Koga Kaori , Nabeshima Kazuki , Aoki Mikiko , Kawakami Takehito , Hamasaki Makoto , Toole Bryan P. , Nakayama Juichiro , Iwasaki Hiroshi
Published: November 2006

Emmprin is a transmembrane glycoprotein on tumor cells that stimulates peritumoral fibroblasts to produce matrix metalloproteinases (MMPs). Emmprin and the induced MMPs play a crucial role in tumor progression, invasion and metastasis of human carcinomas (epithelial malignancies). However, only a few reports have addressed its role in soft tissue sarcomas. This study investigated the expression and role of emmprin in epithelioid sarcoma (ES). Immunoblot studies of 2 ES cell lines showed that they express emmprin, and co‐culture of these ES cells with dermal fibroblasts resulted in upregulation of gelatinase A (MMP‐2) in fibroblasts, as shown by zymography, immunoblotting and enzyme immunoassay. This stimulation was inhibited by an activity‐blocking peptide against emmprin and by antiemmprin antibody. In addition, in vivo, immunohistochemical analysis of 5 ES patient cases demonstrated diffuse emmprin expression in ES cells and MMP‐2 expression in both ES cells and peritumoral fibroblasts. The histopathological findings that peritumoral fibroblasts that were not in direct contact with emmprin‐expressing ES cells exhibit upregulated MMP‐2 prompted us to look for a soluble form of emmprin. Soluble full‐length emmprin released from ES cells was detected in conditioned medium and shown to stimulate MMP‐2 production by fibroblasts. In conclusion, emmprin is expressed in ES in both membrane and soluble forms and stimulates MMP‐2 production via interactions with fibroblasts, which could play a role in ES cell stromal invasion and vascular involvement. © 2006 Wiley‐Liss, Inc.
Reproductive risk factors for incident bladder cancer: Iowa Women's Health Study
Authors: Prizment Anna E. , Anderson Kristin E. , Harlow Bernard L. , Folsom Aaron R.
Published: November 2006

We studied the association between reproductive factors and bladder cancer incidence in a prospective cohort study of 37,459 Iowa women aged 55–69 years and initially free from cancer in 1986. Women reported reproductive history and were followed prospectively through 2003. After adjusting for age and smoking, there was an inverse association between age at menopause and incident bladder cancer (n = 192). Compared with menopause at age ≥≥48, the hazard ratio (HR) of bladder cancer was 1.32 (95% CI; 0.90–1.94) for menopause at 43–47, and 1.60 (95% CI; 1.06–2.39) for ≤≤42 (p‐trend = 0.02). The associations were similar for ages at natural and surgical menopause. In addition, women with a history of bilateral oophorectomy had an increased risk of bladder cancer compared with those who did not undergo bilateral oophorectomy: HR = 1.58 (95% CI; 1.12, 2.22). Finally, there was an indication of a positive association between bladder cancer and shorter lifetime years of ovulation (p‐trend = 0.09). There were no associations between incident bladder cancer and age at first birth, number of births, age at menarche, use of hormone replacement therapy or any other reproductive characteristics. This study provides evidence that increased risk of bladder cancer is associated with earlier age at menopause in postmenopausal women. © 2006 Wiley‐Liss, Inc.
Different types of postmenopausal hormone therapy and mammographic density in Norwegian women
Authors: Bremnes Yngve , Ursin Giske , Bjurstam Nils , Lund Eiliv , Gram Inger Torhild
Published: November 2006

Postmenopausal hormone therapy (HT) is associated with increased risk of breast cancer. The HTs used in Scandinavia is associated with higher risk estimates than those used in most other countries. Mammographic density is one of the strongest risk factors for breast cancer, and possibly an intermediate marker for breast cancer. We decided to examine the relationship between use of different types of HT and mammographic density in Norwegian women. Altogether, 1,007 postmenopausal participants in the governmental mammographic screening program were asked about current and previous HT use. Mammograms were classified according to percent and absolute mammographic density. Overall, current users of HT had on average 3.6% higher mean percent mammographic density when compared with never users (p < 0.001). After adjustment for age at screening, number of children and BMI in a multivariate model, women using the continuous estradiol (E2) plus norethisterone acetate (NETA) combination had a mean percent mammographic density significantly higher than never users (6.1% absolute difference). Those using the continuous E2 plus NETA combination had an 4.8% (absolute difference) higher mean percent mammographic density after <5 years of use when compared with never users, while the corresponding number for ≥5 years of use was 7% (p‐trend < 0.001). We found similar associations when absolute mammographic density was used as the outcome variable. In summary, our study shows a statistical significant positive dose–response association between current use of the continuous E2 plus NETA combination and both measures of mammographic density. © 2006 Wiley‐Liss, Inc.
Age–period–cohort decomposition of aggregate data: an application to US and Japanese household saving rates
Authors: Fukuda Kosei
Published: November 2006

This paper compares two methods of analyzing aggregate data that is classified by period and age. Because there is a linear relationship among age, period, and cohort, it is not possible to distinguish the separate effects without employing an identifying assumption. The first method, which is applied in the economics literature, assumes that period effects are orthogonal to a linear time trend. The second method, which is applied in the statistics literature, assumes that the effect parameters change gradually. Simulation results suggest that the performances of both methods are comparable. The results of applying the second method to household saving rates suggest that period effects had a negligible influence in the United States but considerable influence in Japan. Copyright © 2006 John Wiley & Sons, Ltd.
Mass spectrometric studies on 4‐aryl‐1‐cyclopropyl‐1,2‐dihydropyridinyl derivatives: an examination of a novel fragmentation pathway
Authors: Bissel Philippe , Geherin Skye , Igarashi Kazuo , Gandour Richard D. , Lazar Iulia M. , Castagnoli Jr Neal
Published: November 2006

Examination of the electrospray ionization product ion spectra of 1,2‐dihydropyridinyl and 4‐aryl‐1,2‐dihydropyridinyl derivatives bearing a 1‐cyclopropyl or 1‐trans‐2‐phenylcyclopropyl group has led to the characterization of unexpected fragment ions. For example, the base peak at m/z 156 present in the product ion spectrum of trans‐1‐(2‐phenylcyclopropyl)‐4‐phenyl‐1,2‐dihydropyridine proved not to be the expected 4‐phenylpyridinium species but rather the isomeric 3‐phenyl‐5‐azoniafulvenyl species. The results of studies with a series of structural and isotopically labeled analogs require a novel fragmentation pathway to account for the formation of this and related fragment ions. One possible pathway is based on an initial 1,5‐sigmatropic shift of a cyclopropylmethylene hydrogen atom that is accompanied by opening of the cyclopropyl ring. The resulting eniminium intermediates then fragment to yield the 5‐azoniafulvenyl species. Copyright © 2006 John Wiley & Sons, Ltd.
Methods validation for the determination of trihalomethanes in drinking water
Authors: Culea Monica , Cozar Onuc , Ristoiu Dumitru
Published: November 2006

Trihalomethanes (THMs), chlorinated by‐products in drinking water, have been determined by comparing some analytical methods, based on the following techniques: liquid–liquid extraction‐gas chromatography‐mass spectrometry (LLE‐GC‐MS), headspace‐gas chromatography‐mass spectrometry (headspace‐GC‐MS) and purge and trap‐gas chromatography‐mass spectrometry (PT‐GC‐MS). The mass spectrometer was operated in the SIM mode. The quantitative methods were validated and compared to the ability to identify and to measure reliably the yields of the toxic compounds. Good validation parameters were obtained for each method. Copyright © 2006 John Wiley & Sons, Ltd.
Demographic antecedents and performance consequences of structural holes in work teams
Authors: Balkundi Prasad , Kilduff Martin , Barsness Zoe I. , Michael Judd H.
Published: November 2006

This paper addresses two important questions concerning social fragmentation in work teams. First, from where do disconnections between team members, measured in terms of the proportion of structural holes within the work team, derive? Second, what are the consequences for team performance of having more or less structural holes between team members? In answering the first question, the research investigated whether demographic diversity in teams played a role in predicting the proportion of structural holes in team friendship networks. For 19 teams at a wood products company, there were no effects of ethnic and gender diversity on structural hole proportions. However, age diversity significantly reduced the extent of structural ‘holeyness.’ In investigating the second question, two countervailing tendencies were considered. In the absence of structural holes, teams are likely to be at low risk for new ideas. But fragmented teams in which team members are separated by many structural holes are likely to have difficulty coordinating. The researchers demonstrated a curvilinear effect: a moderate level of structural diversity in teams was positively associated with team performance. Thus, the research suggested that it is structural diversity (measured in terms of the proportion of structural holes) rather than demographic diversity that matters in the prediction of team performance. Copyright © 2006 John Wiley & Sons, Ltd.