bluuebunny/crossref_metadata_2025 huggingface dataset:
Superoxo, μ-peroxo, and μ-oxo complexes from heme/O
2
and heme-Cu/O
2
reactivity: Copper ligand influences in cytochrome
c
oxidase models
Authors: Kim Eunsuk , Helton Matthew E. , Wasser Ian M. , Karlin Kenneth D. , Lu Shen , Huang Hong-wei , Moënne-Loccoz Pierre , Incarvito Christopher D. , Rheingold Arnold L. , Honecker Marcus , Kaderli Susan , Zuberbühler Andreas D.
Published: April 2003

The O
2
-reaction chemistry of 1:1 mixtures of (F
8
)Fe
II
(1; F
8
= tetrakis(2,6-diflurorophenyl)porphyrinate) and [(L

Me
2

N
)Cu
I
]
+
(2; L

Me
2

N
=
N
,
N
-bis{2-[2-(
N
′,
N
′-4-dimethylamino)pyridyl]ethyl}methylamine) is described, to model aspects of the chemistry occurring in cytochrome
c
oxidase. Spectroscopic investigations, along with stopped-flow kinetics, reveal that low-temperature oxygenation of 1/2 leads to rapid formation of a heme-superoxo species (F
8
)Fe
III
-(O

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) (3), whether or not 2 is present. Complex 3 subsequently reacts with 2 to form [(F
8
)Fe
III
–(O

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)–Cu
II
(L

Me
2

N
)]
+
(4), which thermally converts to [(F
8
)Fe
III
–(O)–Cu
II
(L

Me
2

N
)]
+
(5), which has an unusually bent (Fe–O–Cu) bond moiety. Tridentate chelation, compared with tetradentate, is shown to dramatically lower the ν(O–O) values observed in 4 and give rise to the novel structural features in 5.
New clues for platinum antitumor chemistry: Kinetically controlled metal binding to DNA
Authors: Reedijk Jan
Published: April 2003

From the metal ions and metal compounds that are known to bind to DNA, many anticancer Pt(II) and Ru(II)/Ru(III) compounds are known to have ligand-exchange kinetics in the same order of magnitude as the division of tumor cells. The present article discusses this process in detail with special attention to cisplatin and related compounds and the cellular binding sites and processes of such compounds. Detailed platinated DNA structures are presented and discussed in light of the mechanistic studies of metal antitumor compounds. It is now known that platinum antitumor drugs eventually end up on the DNA. However, it remains a challenge to understand how (fast) they reach the DNA and how they are removed. The kinetics of ligand exchange around platinum appear to play a crucial role, and the possible role of other ligands as intermediates, especially those with S-donor sites, is of great interest. New types of Pt compounds with additional functionalities influencing DNA binding and kinetics are discussed in the context of steric and H-bonding properties. A comparison is made with more sterically crowded Ru complexes. The effects on activity and correlations with structural and kinetic properties are clues in understanding the biological activities of these classes of compounds.
The role of copper and protons in heme-copper oxidases: Kinetic study of an engineered heme-copper center in myoglobin
Authors: Sigman Jeffrey A. , Kim Hyeon K. , Zhao Xuan , Carey James R. , Lu Yi
Published: April 2003

To probe the role of copper and protons in heme-copper oxidase (HCO), we have performed kinetic studies on an engineered heme-copper center in sperm whale myoglobin (Leu-29 → His/Phe-43 → His, called Cu
B
Mb) that closely mimics the heme-copper center in HCO. In the absence of metal ions, the engineered Cu
B
center in Cu
B
Mb decreases the O
2
binding affinity of the heme. However, addition of Ag(I), a redox-inactive mimic of Cu(I), increases the O
2
-binding affinity. More importantly, copper ion in the Cu
B
center is essential for O
2
reduction, as no O
2
reduction can be observed in copper-free, Zn(II), or Ag(I) derivatives of Cu
B
Mb. Instead of producing a ferryl-heme as in HCO, the Cu
B
Mb generates verdoheme because the engineered Cu
B
Mb may lack a hydrogen bonding network that delivers protons to promote the heterolytic O—O cleavage necessary for the formation of ferryl-heme. Reaction of oxidized Cu
B
Mb with H
2
O
2
, a species equivalent in oxidation state to 2e
−
, reduced O
2
but, possessing the extra protons, resulted in ferryl-heme formation, as in HCO. The results showed that the Cu
B
center plays a critical role in O
2
binding and reduction, and that proton delivery during the O
2
reduction is important to avoid heme degradation and to promote the HCO reaction.
Histone deacetylase inhibitors prevent oxidative neuronal death independent of expanded polyglutamine repeats via an Sp1-dependent pathway
Authors: Ryu Hoon , Lee Junghee , Olofsson Beatrix A. , Mwidau Aziza , Deodoglu Alpaslan , Escudero Maria , Flemington Erik , Azizkhan-Clifford Jane , Ferrante Robert J. , Ratan Rajiv R.
Published: April 2003

Oxidative stress is believed to be an important mediator of neurodegeneration. However, the transcriptional pathways induced in neurons by oxidative stress that activate protective gene responses have yet to be fully delineated. We report that the transcription factor Sp1 is acetylated in response to oxidative stress in neurons. Histone deacetylase (HDAC) inhibitors augment Sp1 acetylation, Sp1 DNA binding, and Sp1-dependent gene expression and confer resistance to oxidative stress-induced deathin vitroandin vivo. Sp1 activation is necessary for the protective effects of HDAC inhibitors. Together, these results demonstrate that HDAC inhibitors inhibit oxidative death independent of polyglutamine expansions by activating an Sp1-dependent adaptive response.
Ring-like pore structures of SecA: Implication for bacterial protein-conducting channels
Authors: Wang Hong-Wei , Chen Yong , Yang Hsiuchin , Chen Xianchuan , Duan Ming-Xing , Tai Phang C. , Sui Sen-Fang
Published: April 2003

SecA, an essential component of the general protein secretion pathway of bacteria, is present in
Escherichia coli
as soluble and membrane-integral forms. Here we show by electron microscopy that SecA assumes two characteristic forms in the presence of phospholipid monolayers: dumbbell-shaped elongated structures and ring-like pore structures. The ring-like pore structures with diameters of 8 nm and holes of 2 nm are found only in the presence of anionic phospholipids. These ring-like pore structures with larger 3- to 6-nm holes (without staining) were also observed by atomic force microscopic examination. They do not form in solution or in the presence of uncharged phosphatidylcholine. These ring-like phospholipid-induced pore-structures may form the core of bacterial protein-conducting channels through bacterial membranes.
Property Γ factors and the Hochschild cohomology problem
Authors: Christensen Erik , Pop Florin , Sinclair Allan M. , Smith Roger R.
Published: April 2003

The main result of this article is that the
k
th continuous Hochschild cohomology groups

H
k

(ℳ, ℳ) and

H
k

(ℳ,
B
(
H
)) of a von Neumann factor ℳ ⊆
B
(
H
) of type
II
1
with property Γ are 0 for all positive integers
k
. The method of proof involves the construction of hyperfinite subfactors with special properties and a new inequality of Grothendieck type for multilinear maps. We prove joint continuity in the ∥⋅∥
2
norm of separately ultraweakly continuous multilinear maps and combine these results to reduce to the case of completely bounded cohomology, which is already solved.
Mitochondrial pathology and apoptotic muscle degeneration in
Drosophila parkin
mutants
Authors: Greene Jessica C. , Whitworth Alexander J. , Kuo Isabella , Andrews Laurie A. , Feany Mel B. , Pallanck Leo J.
Published: April 2003

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in the substantia nigra. Several lines of evidence strongly implicate mitochondrial dysfunction as a major causative factor in PD, although the molecular mechanisms responsible for mitochondrial dysfunction are poorly understood. Recently, loss-of-function mutations in the
parkin
gene, which encodes a ubiquitin-protein ligase, were found to underlie a familial form of PD known as autosomal recessive juvenile parkinsonism (AR-JP). To gain insight into the molecular mechanism responsible for selective cell death in AR-JP, we have created a
Drosophila
model of this disorder.
Drosophila parkin
null mutants exhibit reduced lifespan, locomotor defects, and male sterility. The locomotor defects derive from apoptotic cell death of muscle subsets, whereas the male sterile phenotype derives from a spermatid individualization defect at a late stage of spermatogenesis. Mitochondrial pathology is the earliest manifestation of muscle degeneration and a prominent characteristic of individualizing spermatids in
parkin
mutants. These results indicate that the tissue-specific phenotypes observed in
Drosophila parkin
mutants result from mitochondrial dysfunction and raise the possibility that similar mitochondrial impairment triggers the selective cell loss observed in AR-JP.
Salmochelins, siderophores of
Salmonella enterica
and uropathogenic
Escherichia coli
strains, are recognized by the outer membrane receptor IroN
Authors: Hantke K. , Nicholson G. , Rabsch W. , Winkelmann G.
Published: April 2003

Members of a family of catecholate siderophores, called salmochelins, were isolated by reversed-phase HPLC from
Salmonella enterica
serotype Typhimurium and structurally characterized by Fourier transform ion cyclotron resonance–MS/MS and GC–MS. The tentative structure of salmochelin 1 contained two 2,3- dihydroxybenzoylserine moieties bridged by a glucose residue, bound to the serine hydroxyl group of one moiety and the carboxylate of the second moiety. Salmochelin 2 contained in addition a second glucose residue linked to a third 2,3-dihydroxybenzoylserine moiety. Salmochelins were not produced by an
iroBC
mutant, which indicated that the IroB protein might be responsible for the glucosyl transfer predicted by sequence similarities to known glycosyltransferases. Uptake experiments with radiolabeled
55
Fe-salmochelin and growth promotion tests with salmochelins showed that the IroN outer membrane receptor, encoded in the
iroA
locus of
S. enterica
and uropathogenic
Escherichia coli
strains, was the main receptor for ferric salmochelin transport.
Floating plant dominance as a stable state
Authors: Scheffer Marten , Szabó Sándor , Gragnani Alessandra , van Nes Egbert H. , Rinaldi Sergio , Kautsky Nils , Norberg Jon , Roijackers Rudi M. M. , Franken Rob J. M.
Published: April 2003

Invasion by mats of free-floating plants is among the most important threats to the functioning and biodiversity of freshwater ecosystems ranging from temperate ponds and ditches to tropical lakes. Dark, anoxic conditions under thick floating-plant cover leave little opportunity for animal or plant life, and they can have large negative impacts on fisheries and navigation in tropical lakes. Here, we demonstrate that floating-plant dominance can be a self-stabilizing ecosystem state, which may explain its notorious persistence in many situations. Our results, based on experiments, field data, and models, represent evidence for alternative domains of attraction in ecosystems. An implication of our findings is that nutrient enrichment reduces the resilience of freshwater systems against a shift to floating-plant dominance. On the other hand, our results also suggest that a single drastic harvest of floating plants can induce a permanent shift to an alternative state dominated by rooted, submerged growth forms.
Metal stoichiometry and functional studies of the diphtheria toxin repressor
Authors: Spiering Michelle M. , Ringe Dagmar , Murphy John R. , Marletta Michael A.
Published: April 2003

Diphtheria toxin repressor (DtxR) is a transition metal ion-activated repressor in
Corynebacterium diphtheriae
. DtxR is an iron sensor; metal-bound DtxR represses transcription of genes downstream of the
tox
operator. Wild-type DtxR [DtxR(wt)] and several mutant forms were overexpressed and purified from
Escherichia coli
. DtxR was isolated without bound metal. Metal reconstitution gave a binding stoichiometry of 2 per monomer for DtxR(wt) and 1 per monomer for DtxR(H79A) and DtxR(M10A). DNA binding of DtxR(H79A) and DtxR(M10A) indicates that metal site 2 is essential for activity. Metal binding lowers the dimerization
K
d
of DtxR from low micromolar to 33 nM. Gel electrophoretic mobility-shift assays show that Fe
2+
and not Fe
3+
activates DtxR for DNA binding. This finding suggests that gene regulation by DtxR may be sensitive not only to iron levels but also to redox state of the iron. Mutations in the
tox
operator sequence indicate that DtxR dimers binding to DNA may be highly cooperative.
The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment
Authors: Thiébault Karine , Mazelin Laetitia , Pays Laurent , Llambi Fabien , Joly Marie-Odile , Scoazec Jean-Yves , Saurin Jean-Christophe , Romeo Giovanni , Mehlen Patrick
Published: April 2003

The three mammalian receptors UNC5H1, UNC5H2, and UNC5H3 (also named UNC5A, UNC5B, and UNC5C in human) that belong to the family of the netrin-1 receptors, UNC5H, were initially proposed as mediators of the chemorepulsive effect of netrin-1 on specific axons. However, they were also recently shown to act as dependence receptors. Such receptors induce apoptosis when unbound to their ligand. We show here that the expression of the human UNC5A, UNC5B, or UNC5C is down-regulated in multiple cancers including colorectal, breast, ovary, uterus, stomach, lung, or kidney cancers. In colorectal tumors, this down-regulation is associated with loss of heterozygosity occurring within
UNC5A
,
UNC5B
, and
UNC5C
genes but may also be partially related to epigenetic processes because histone deacetylase inhibitor increased
UNC5C
expression in various cancer cell lines. Moreover, sequencing of
UNC5C
gene in patients with colorectal tumors revealed the presence of missense mutations. The loss/reduction of expression may be a crucial mechanism for tumorigenicity because the expression of UNC5H1, UNC5H2, or UNC5H3 inhibits tumor cell anchorage-independent growth and invasion. Moreover, these hallmarks of malignant transformation can be restored by netrin-1 addition or apoptosis inhibition. Hence, UNC5H1, UNC5H2, and UNC5H3 receptors may represent tumor suppressors that inhibit tumor extension outside the region of netrin-1 availability by inducing apoptosis.
The bioinorganic chemistry of iron in oxygenases and supramolecular assemblies
Authors: Groves John T.
Published: April 2003

The bioinorganic chemistry of iron is central to life processes. Organisms must recruit iron from their environment, control iron storage and trafficking within cells, assemble the complex, iron-containing redox cofactors of metalloproteins, and manage a myriad of biochemical transformations by those enzymes. The coordination chemistry and the variable oxidation states of iron provide the essential mechanistic machinery of this metabolism. Our current understanding of several aspects of the chemistry of iron in biology are discussed with an emphasis on the oxygen activation and transfer reactions mediated by heme and nonheme iron proteins and the interactions of amphiphilic iron siderophores with lipid membranes.
Binding and release of iron by gel-encapsulated human transferrin: Evidence for a conformational search
Authors: Navati Mahantesh S. , Samuni Uri , Aisen Philip , Friedman Joel M.
Published: April 2003

Human transferrin is a single-chain bilobal protein with each of the two similar but not identical lobes in turn composed of two domains. Each lobe may assume one of two stable structural conformations, open or closed, determined by a rigid rotation of the domains with respect to each other. In solution, the transformation of a lobe between open and closed conformations is associated with the release or binding of an Fe(III) ion. The results of the present study indicate that encapsulation of transferrin within a porous sol-gel matrix allows for a dramatic expansion, to days or weeks, of this interconversion time period, thus providing an opportunity to probe heretofore inaccessible transient intermediates. Sol-gel-encapsulated iron-free transferrin samples are prepared by using two protocols. In the first protocol, the equilibrium form of apotransferrin is encapsulated in the sol-gel matrix, whereas in the second protocol holotransferrin is first encapsulated and then iron is removed from the protein. Results of kinetic and spectroscopic studies allow for distinguishing between two models for iron binding. In the first, iron is assumed to bind to amino acid ligands of one domain, inducing a rigid rotation of the second domain to effect closure of the interdomain cleft. In the second, iron undertakes a conformational search among the thermally accessible states of the lobe, “choosing” the state which most nearly approximates the stable closed state when iron is bound. Our experimental results support the second mechanism.
Amino acid variant in the kinase binding domain of dual-specific A kinase-anchoring protein 2: A disease susceptibility polymorphism
Authors: Kammerer Stefan , Burns-Hamuro Lora L. , Ma Yuliang , Hamon Sara C. , Cànaves Jaume M. , Shi Michael M. , Nelson Matthew R. , Sing Charles F. , Cantor Charles R. , Taylor Susan S. , Braun Andreas
Published: April 2003

The focus of human genetics in recent years has shifted toward identifying genes that are involved in the development of common diseases such as cancer, diabetes, cardiovascular diseases, and Alzheimer's disease. Because many complex diseases are late-onset, the frequencies of disease susceptibility alleles are expected to decrease in the healthy elderly individuals of the population at large because of their contribution to disease morbidity and/or mortality. To test this assumption, we compared allele frequencies of 6,500 single-nucleotide polymorphisms (SNPs) located in ≈5,000 genes between DNA pools of age-stratified healthy, European-American individuals. A SNP that results in an amino acid change from Ile to Val in the dual-specific A kinase-anchoring protein 2 (
d
-AKAP2) gene, showed the strongest correlation with age. Subsequent analysis of an independent sample indicated that the Val variant was associated with a statistically significant decrease in the length of the electrocardiogram PR interval. The Ile/Val SNP is located in the A-kinase-binding domain. An
in vitro
binding assay revealed that the Ile variant bound ≈3-fold weaker to the protein kinase A (PKA)-RIα isoform than the Val variant. This decreased affinity resulted in alterations in the subcellular distribution of the recombinantly expressed PKA-RIα isoform. Our study suggests that alterations in PKA-RIα subcellular localization caused by variation in
d
-AKAP2 may have a negative health prognosis in the aging population, which may be related to cardiac dysfunction. Age-stratified samples appear to be useful for screening SNPs to identify functional gene variants that have an impact on health.
Lymphocyte surface thiol levels
Authors: Sahaf Bita , Heydari Kartoosh , Herzenberg Leonard A. , Herzenberg Leonore A.
Published: April 2003

Recent studies have implicated reduced thiols (cysteine −SH) in the function of individual cell surface proteins. Studies presented here demonstrate that the overall level of reduced thiols on cell surface molecules differs on individual subsets of peripheral blood mononuclear cells and that these levels can be manipulated
in vitro
by altering the level of intracellular glutathione (iGSH). To quantitate cell surface thiols, we have developed a Hi-D (11-color) fluorescence-activated cell sorter method in which we covalently couple a fluorescent molecule, Alexa-maleimide, to free (reduced) –SH groups on proteins or other molecules exposed on the cell surface (exofacial membrane). In addition, to reveal changes in cell surface thiol levels in response to various
in vitro
treatments, we used a pair of fluorescent Alexa dyes with distinct excitation and emission spectra to stain the cells before and after treatments. These
in vitro
studies demonstrate that decreasing iGSH, by specifically inhibiting its synthesis, decreases cell surface molecule thiols (csm−SH) and that preventing loss of iGSH also prevents loss of csm−SH. However, examination of peripheral blood mononuclear cell subsets tested immediately after isolation from healthy or HIV-infected subjects failed to reveal a similar relationship between internal iGSH and csm−SH. Although there is a relatively wide variation between individuals in both csm−SH and iGSH, there is no correlation between median iGSH and csm−SH compared for 22 healthy and 36 HIV-infected subjects. Collectively, our findings indicate that local environment plays a greater role in determining the redox status of cell surface molecules than the internal redox status of the cells.
Designing isoform-specific peptide disruptors of protein kinase A localization
Authors: Burns-Hamuro Lora L. , Ma Yuliang , Kammerer Stefan , Reineke Ulrich , Self Chris , Cook Charles , Olson Gary L. , Cantor Charles R. , Braun Andreas , Taylor Susan S.
Published: April 2003

A kinase-anchoring proteins (AKAPs) coordinate cAMP-mediated signaling by binding and localizing cAMP-dependent protein kinase (PKA), using an amphipathic helical docking motif. Peptide disruptors of PKA localization that mimic this helix have been used successfully to assess the involvement of PKA in specific signaling pathways. However, these peptides were developed as disruptors for the type II regulatory subunit (RII) even though both RI and RII isoforms can bind to AKAPs and have discrete functions. To evaluate the effects of each localized isoform, we designed peptides that specifically bind to either RI or RII. Using a peptide array, we have defined the minimal binding sequence of dual specific-AKAP 2 (
d
-AKAP2), which binds tightly to both RI and RII. Side-chain requirements for affinity and isoform specificity were evaluated by using a peptide substitution array where each position along the A kinase binding domain of
d
-AKAP2 was substituted by the other 19
l
-amino acids. This array comprises 513 single-site substitution analogs of the
d
-AKAP2 sequence. Peptides containing single and multiple mutations were evaluated in a quantitative fluorescence binding assay and a cell-based colocalization assay. This strategy has allowed us to design peptides with high affinity (
K
D
= 1–2 nM) and high specificity for RIα versus RIIα. These isoform-specific peptides will be invaluable tools to evaluate functional differences between localized RI and RII PKA and are RIα-specific disruptors. This array-based analysis also provides a foundation for biophysical analysis of this docking motif.
European Prospective Investigation into Cancer and Nutrition (EPIC): study populations and data collection
Authors: Riboli E , Hunt KJ , Slimani N , Ferrari P , Norat T , Fahey M , Charrondière UR , Hémon B , Casagrande C , Vignat J , Overvad K , Tjønneland A , Clavel-Chapelon F , Thiébaut A , Wahrendorf J , Boeing H , Trichopoulos D , Trichopoulou A , Vineis P , Palli D , Bueno-de-Mesquita HB , Peeters PHM , Lund E , Engeset D , González CA , Barricarte A , Berglund G , Hallmans G , Day NE , Key TJ , Kaaks R , Saracci R
Published: March 2003

The European Prospective Investigation into Cancer and Nutrition (EPIC) is an ongoing multi-centre prospective cohort study designed to investigate the relationship between nutrition and cancer, with the potential for studying other diseases as well. The study currently includes 519 978 participants (366 521 women and 153 457 men, mostly aged 35–70 years) in 23 centres located in 10 European countries, to be followed for cancer incidence and cause-specific mortality for several decades. At enrolment, which took place between 1992 and 2000 at each of the different centres, information was collected through a non-dietary questionnaire on lifestyle variables and through a dietary questionnaire addressing usual diet. Anthropometric measurements were performed and blood samples taken, from which plasma, serum, red cells and buffy coat fractions were separated and aliquoted for long-term storage, mostly in liquid nitrogen. To calibrate dietary measurements, a standardised, computer-assisted 24-hour dietary recall was implemented at each centre on stratified random samples of the participants, for a total of 36 900 subjects. EPIC represents the largest single resource available today world-wide for prospective investigations on the aetiology of cancers (and other diseases) that can integrate questionnaire data on lifestyle and diet, biomarkers of diet and of endogenous metabolism (e.g. hormones and growth factors) and genetic polymorphisms. First results of case–control studies nested within the cohort are expected early in 2003. The present paper provides a description of the EPIC study, with the aim of simplifying reference to it in future papers reporting substantive or methodological studies carried out in the EPIC cohort.
European Prospective Investigation into Cancer and Nutrition (EPIC) calibration study: rationale, design and population characteristics
Authors: Slimani N , Kaaks R , Ferrari P , Casagrande C , Clavel-Chapelon F , Lotze G , Kroke A , Trichopoulos D , Trichopoulou A , Lauria C , Bellegotti M , Ocké MC , Peeters PHM , Engeset D , Lund E , Agudo A , Larrañaga N , Mattisson I , Andren C , Johansson I , Davey G , Welch AA , Overvad K , Tjønneland A , van Staveren WA , Saracci R , Riboli E
Published: March 2003

The European Prospective Investigation into Cancer and Nutrition (EPIC), which covers a large cohort of half a million men and women from 23 European centres in 10 Western European countries, was designed to study the relationship between diet and the risk of chronic diseases, particularly cancer. Information on usual individual dietary intake was assessed using different validated dietary assessment methods across participating countries. In order to adjust for possible systematic over- or underestimation in dietary intake measurements and correct for attenuation bias in relative risk estimates, a calibration approach was developed. This approach involved an additional dietary assessment common across study populations to re-express individual dietary intakes according to the same reference scale. A single 24-hour diet recall was therefore collected, as the EPIC reference calibration method, from a stratified random sample of 36 900 subjects from the entire EPIC cohort, using a software program (EPIC-SOFT) specifically designed to standardise the dietary measurements across study populations. This paper describes the design and populations of the calibration sub-studies set up in the EPIC centres. In addition, to assess whether the calibration sub-samples were representative of the entire group of EPIC cohorts, a series of subjects’ characteristics known possibly to influence dietary intakes was compared in both population groups. This was the first time that calibration sub-studies had been set up in a large multi-centre European study. These studies showed that, despite certain inherent methodological and logistic constraints, a study design such as this one works relatively well in practice. The average response in the calibration study was 78.3% and ranged from 46.5% to 92.5%. The calibration population differed slightly from the overall cohort but the differences were small for most characteristics and centres. The overall results suggest that, after adjustment for age, dietary intakes estimated from calibration samples can reasonably be interpreted as representative of the main cohorts in most of the EPIC centres.
Overweight, obesity and fat distribution in 50- to 64-year-old participants in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Haftenberger M , Lahmann PH , Panico S , Gonzalez CA , Seidell JC , Boeing H , Giurdanella MC , Krogh V , Bueno-de-Mesquita HB , Peeters PHM , Skeie G , Hjartåker A , Rodriguez M , Quirós JR , Berglund G , Janlert U , Khaw KT , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Tehard B , Miller AB , Klipstein-Grobusch K , Benetou V , Kiriazi G , Riboli E , Slimani N
Published: March 2003

Objective:

To describe anthropometric characteristics of participants of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design:

A cross-sectional analysis of baseline data of a European prospective cohort study.

Subjects:

This analysis includes study populations from 25 centres in nine European countries. The British populations comprised both a population-based and a ‘health-conscious’ group. The analysis was restricted to 83 178 men and 163 851 women aged 50–64 years, this group being represented in all centres.

Methods:

Anthropometric examinations were undertaken by trained observers using standardised methods and included measurements of weight, height, and waist and hip circumferences. In the ‘health-conscious’ group (UK), anthropometric measures were predicted from self-reports.

Results:

Except in the ‘health-conscious’ group (UK) and in the French centres, mean body mass index (BMI) exceeded 25.0 kg m-2. The prevalence of obesity (BMI≥30 kg m-2) varied from 8% to 40% in men, and from 5% to 53% in women, with high prevalences (>25%) in the centres from Spain, Greece, Ragusa and Naples (Italy) and the lowest prevalences (<10%) in the French centres and the ‘health-conscious’ group (UK). The prevalence of a large waist circumference or a high waist-to-hip ratio was high in centres from Spain, Greece, Ragusa and Naples (Italy) and among women from centres in Germany and Bilthoven (The Netherlands).

Conclusions:

Anthropometric measures varied considerably within the EPIC population. These data provide a strong base for further investigation of anthropometric measures in relation to the risk of chronic diseases, especially cancer.
Physical activity of subjects aged 50–64 years involved in the European Prospective Investigation into Cancer and Nutrition (EPIC)
Authors: Haftenberger M , Schuit AJ , Tormo MJ , Boeing H , Wareham N , Bueno-de-Mesquita HB , Kumle M , Hjartåker A , Chirlaque MD , Ardanaz E , Andren C , Lindahl B , Peeters PHM , Allen NE , Overvad K , Tjønneland A , Clavel-Chapelon F , Linseisen J , Bergmann MM , Trichopoulou A , Lagiou P , Salvini S , Panico S , Riboli E , Ferrari P , Slimani N
Published: March 2003

Objective:

To describe physical activity of participants in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design:

A cross-sectional analysis of baseline data of a European prospective cohort study.

Subjects:

This analysis was restricted to participants in the age group 50–64 years, which was represented in all EPIC centres. It involved 236 386 participants from 25 centres in nine countries. In each EPIC centre, physical activity was assessed by standardised and validated questions. Frequency distribution of type of professional activity and participation in non-professional activities, and age-adjusted means, medians and percentiles of time dedicated to non-professional activities are presented for men and women from each centre.

Results:

Professional activity was most frequently classified as sedentary or standing in all centres. There was a wide variation regarding participation in different types of non-professional activities and time dedicated to these activities across EPIC centres. Over 80% of all EPIC participants engaged in walking, while less than 50% of the subjects participated in sport. Total time dedicated to recreational activities was highest among the Dutch participants and lowest among men from Malmö (Sweden) and women from Naples (Italy). In all centres, total time dedicated to recreational activity in the summer was higher than in the winter. Women from southern Europe spent the most time on housekeeping.

Conclusions:

There is a considerable variation of physical activity across EPIC centres. This variation was especially evident for recreational activities in both men and women.
Consumption of vegetables, fruit and other plant foods in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts from 10 European countries
Authors: Agudo A , Slimani N , Ocké MC , Naska A , Miller AB , Kroke A , Bamia C , Karalis D , Vineis P , Palli D , Bueno-de-Mesquita HB , Peeters PHM , Engeset D , Hjartåker A , Navarro C , Garcia C Martínez , Wallström P , Zhang JX , Welch AA , Spencer E , Stripp C , Overvad K , Clavel-Chapelon F , Casagrande C , Riboli E
Published: March 2003

Objective:

To describe and compare the consumption of the main groups and sub-groups of vegetables and fruits (V&F) in men and women from the centres participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design:

Cross-sectional analysis. Dietary intake was assessed by means of a 24-hour dietary recall using computerised interview software and standardised procedures. Crude and adjusted means were computed for the main groups and sub-groups of V&F by centre, separately for men and women. Adjusted means by season, day of the week and age were estimated using weights and covariance analysis.

Setting:

Twenty-seven centres in 10 European countries participating in the EPIC project.

Subjects:

In total, 35 955 subjects (13 031 men and 22 924 women), aged 35–74 years, randomly selected from each EPIC cohort.

Results:

The centres from southern countries had the highest consumption of V&F, while the lowest intake was seen in The Netherlands and Scandinavia for both genders. These differences were more evident for fruits, particularly citrus. However, slightly different patterns arose for some sub-groups of vegetables, such as root vegetables and cabbage. Adjustment for body mass index, physical activity, smoking habits and education did not substantially modify the mean intakes of vegetables and fruits.

Conclusions:

Total vegetable and fruit intake follows a south–north gradient in both genders, whereas for several sub-groups of vegetables a different geographic distribution exists. Differences in mean intake of V&F by centre were not explained by lifestyle factors associated with V&F intake.
Food sources of carbohydrates in a European cohort of adults
Authors: Wirfält E , McTaggart A , Pala V , Gullberg B , Frasca G , Panico S , Bueno-de-Mesquita HB , Peeters PHM , Engeset D , Skeie G , Chirlaque MD , Amiano P , Lundin E , Mulligan A , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Linseisen J , Nöthlings U , Polychronopoulos E , Georga K , Charrondière UR , Slimani N
Published: March 2003

Objective:

To describe the average consumption of carbohydrate-providing food groups among study centres of the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods:

Of the 27 redefined EPIC study centres, 19 contributed subjects of both genders and eight centres female participants only (men,n=13 031; women,n=22924, after exclusion of subjects under 35 and over 74 years of age from the original 36 900 total). Dietary data were obtained using the 24-hour recall methodology using the EPIC-SOFT software. The major sources of dietary carbohydrate were identified, and 16 food groups were examined.

Results:

The 10 food groups contributing most carbohydrate were bread; fruit; milk and milk products; sweet buns, cakes and pies; potato; sugar and jam; pasta and rice; vegetables and legumes; crispbread; and fruit and vegetable juices. Consumption of fruits as well as vegetables and legumes was higher in southern compared with northern centres, while soft drinks consumption was higher in the north. Italian centres had high pasta and rice consumption, but breakfast cereal, potato, and sweet buns, cakes and pies were higher in northern centres. In Sweden, lower bread consumption was balanced with a higher consumption of crispbread, and with sweet buns, cakes and pies. Overall, men consumed higher amounts of vegetables and legumes, bread, soft drinks, potatoes, pasta and rice, breakfast cereal and sugar and jam than women, but fruit consumption appeared more frequent in women.

Conclusion:

The study supports the established idea that carbohydrate-rich foods chosen in northern Europe are different from those in the Mediterranean region. When comparing and interpreting diet–disease relationships across populations, researchers need to consider all types of foods.
Soy product consumption in 10 European countries: the European Prospective Investigation into Cancer and Nutrition (EPIC) study
Authors: Keinan-Boker L , Peeters PHM , Mulligan AA , Navarro C , Slimani N ,   EPIC Study Group on Soy Consumption:, Mattisson I , Lundin E , McTaggart A , Allen NE , Overvad K , Tjønneland A , Clavel-Chapelon F , Linseisen J , Haftenberger M , Lagiou P , Kalapothaki V , Evangelista A , Frasca G , Bueno-de-Mesquita HB , van der Schouw YT , Engeset D , Skeie G , Tormo MJ , Ardanaz E , Charrondière UR , Riboli E
Published: March 2003

Objective:

The aim of this study was to describe the variation of soy product intake in 10 European countries by using a standardised reference dietary method. A subsidiary aim was to characterise the pattern of soy consumption among a sub-group of participants with a habitual health-conscious lifestyle (HHL), i.e. non-meat eaters who are fish eaters, vegetarians and vegans.

Design:

A 24-hour dietary recall interview (24-HDR) was conducted among a sample (5–12%) of all cohorts (n = 36 900) in the European Prospective Investigation into Cancer and Nutrition (EPIC). Study participants totalled 35 955 after exclusion of subjects younger than 35 or older than 74 years of age. Soy products were subdivided into seven sub-groups by similarity. Distribution of consumption and crude and adjusted means of intake were computed per soy product group across countries. Intake of soy products was also investigated among participants with an HHL.

Results:

In total, 195 men and 486 women reported consuming soy products in the 24-HDR interview. Although soy product intake was generally low across all countries, the highest intake level was observed in the UK, due to over-sampling of a large number of participants with an HHL. The most frequently consumed soy foods were dairy substitutes in the UK and France and beans and sprouts among mid-European countries. For both genders, the sub-group of soy dairy substitutes was consumed in the highest quantities (1.2 g day−1 for men; 1.9 g day−1 for women). Participants with an HHL differed substantially from others with regard to demographic, anthropometric and nutritional factors. They consumed higher quantities of almost all soy product groups.

Conclusions:

Consumption of soy products is low in centres in Western Europe. Soy dairy substitutes are most frequently consumed. Participants with an HHL form a distinct sub-group with higher consumptions of fruit, vegetables, legumes, cereals and soy products compared with the other participants.
Consumption of added fats and oils in the European Prospective Investigation into Cancer and Nutrition (EPIC) centres across 10 European countries as assessed by 24-hour dietary recalls
Authors: Linseisen J , Bergström E , Gafá L , González CA , Thiébaut A , Trichopoulou A , Tumino R , Sánchez C Navarro , Garcia C Martínez , Mattisson I , Nilsson S , Welch A , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Kesse E , Miller AB , Schulz M , Botsi K , Naska A , Sieri S , Sacerdote C , Ocké MC , Peeters PHM , Skeie G , Engeset D , Charrondière UR , Slimani N
Published: March 2003

Objective:

To evaluate the consumption of added fats and oils across the European centres and countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Design and setting:

24-Hour dietary recalls were collected by means of standardised computer-guided interviews in 27 redefined EPIC centres across 10 European countries.

Subjects:

From an initial number of 36 900 subjects, single dietary recalls from 22 924 women and 13 031 men in the age range of 35–74 years were included.

Results:

Mean daily intake of added fats and oils varied between 16.2 g (Varese, Italy) and 41.1 g (Malmö, Sweden) in women and between 24.7 g (Ragusa, Italy) and 66.0 g (Potsdam, Germany) in men. Total mean lipid intake by consumption of added fats and oils, including those used for sauce preparation, ranged between 18.3 (Norway) and 37.2 g day−1 (Greece) in women and 28.4 (Heidelberg, Germany) and 51.2 g day−1 (Greece) in men. The Mediterranean EPIC centres with high olive oil consumption combined with low animal fat intake contrasted with the central and northern European centres where fewer vegetable oils, more animal fats and a high proportion of margarine were consumed. The consumption of added fats and oils of animal origin was highest in the German EPIC centres, followed by the French. The contribution of added fats and oils to total energy intake ranged from 8% in Norway to 22% in Greece.

Conclusions:

The results demonstrate a high variation in dietary intake of added fats and oils in EPIC, providing a good opportunity to elucidate the role of dietary fats in cancer aetiology.
Meat consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts: results from 24-hour dietary recalls
Authors: Linseisen J , Kesse E , Slimani N , Bueno-de-Mesquita HB , Ocké MC , Skeie G , Kumle M , Iraeta M Dorronsoro , Gómez P Morote , Janzon L , Stattin P , Welch AA , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Miller AB , Klipstein-Grobusch K , Lagiou P , Kalapothaki V , Masala G , Giurdanella MC , Norat T , Riboli E
Published: March 2003

Objective:

To evaluate meat intake patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts.

Design and setting:

24-Hour dietary recalls were assessed within the framework of a prospective cohort study in 27 centres across 10 European countries by means of standardised computer-assisted interviews.

Subjects:

In total, 22 924 women and 13 031 men aged 35–74 years.

Results:

Mean total meat intake was lowest in the ‘health-conscious’ cohort in the UK (15 and 21 g day−1 in women and men, respectively) and highest in the north of Spain, especially in San Sebastian (124 and 234 g day−1, respectively). In the southern Spanish centres and in Naples (Italy), meat consumption was distinctly lower than in the north of these countries. Central and northern European centres/countries showed rather similar meat consumption patterns, except for the British and French cohorts. Differences in the intake of meat sub-groups (e.g. red meat, processed meat) across EPIC were even higher than found for total meat intake. With a few exceptions, the Mediterranean EPIC centres revealed a higher proportion of beef/veal and poultry and less pork or processed meat than observed in central or northern European centres. The highest sausage consumption was observed for the German EPIC participants, followed by the Norwegians, Swedish, Danish and Dutch.

Conclusions:

The results demonstrate distinct differences in meat consumption patterns between EPIC centres across Europe. This is an important prerequisite for obtaining further insight into the relationship between meat intake and the development of chronic diseases.
Consumption of dairy products in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort: data from 35955 24-hour dietary recalls in 10 European countries
Authors: Hjartåker A , Lagiou A , Slimani N , Lund E , Chirlaque MD , Vasilopoulou E , Zavitsanos X , Berrino F , Sacerdote C , Ocké MC , Peeters PHM , Engeset D , Skeie G , Aller A , Amiano P , Berglund G , Nilsson S , McTaggart A , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Linseisen J , Schulz M , Hemon B , Riboli E
Published: March 2003

Objectives:

To describe and compare the consumption of dairy products in cohorts included in the European Prospective Investigation into Cancer and Nutrition (EPIC).

Methods:

Data from single 24-hour dietary recall interviews collected through a highly standardised computer-based program (EPIC-SOFT) in 27 redefined centres in 10 European countries between 1995 and 2000. From a total random sample of 36 900, 22 924 women and 13 031 men were selected after exclusion of subjects under 35 and over 74 years of age.

Results:

A high total consumption of dairy products was reported in most of the centres in Spain and in the UK cohort sampled from the general population, as well as in the Dutch, Swedish and Danish centres. A somewhat low consumption was reported in the Greek centre and in some of the Italian centres (Ragusa and Turin). In all centres and for both sexes, milk constituted the dairy sub-group with the largest proportion (in grams) of total dairy consumption, followed by yoghurt and other fermented milk products, and cheese. Still, there was a wide range in the contributions of the different dairy sub-groups between centres. The Spanish and Nordic centres generally reported a high consumption of milk, the Swedish and Dutch centres reported a high consumption of yoghurt and other fermented milk products, whereas the highest consumption of cheese was reported in the French centres.

Conclusion:

The results demonstrate both quantitative and qualitative disparities in dairy product consumption among the EPIC centres. This offers a sound starting point for analyses of associations between dairy intake and chronic diseases such as cancer.
Variability of fish consumption within the 10 European countries participating in the European Investigation into Cancer and Nutrition (EPIC) study
Authors: Welch AA , Lund E , Amiano P , Dorronsoro M , Brustad M , Kumle M , Rodriguez M , Lasheras C , Janzon L , Jansson J , Luben R , Spencer EA , Overvad K , Tjønneland A , Clavel-Chapelon F , Linseisen J , Klipstein-Grobusch K , Benetou V , Zavitsanos X , Tumino R , Galasso R , Bueno-de-Mesquita HB , Ocké MC , Charrondière UR , Slimani N
Published: March 2003

Objective:

To describe and compare the consumption of total fish (marine foods) and the fish sub-groups – white fish, fatty fish, very fatty fish, fish products and crustacea, in participants from the European Investigation into Cancer and Nutrition (EPIC) study.

Design:

Cross-sectional analysis of dietary intake using a computerised standardised 24-hour recall interview. Crude means, means and standard errors adjusted by age, season and day of the week were calculated, stratified by centre and gender.

Setting:

Twenty-seven redefined centres in the 10 European countries participating in the EPIC study.

Subjects:

In total, 35 955 subjects (13 031 men and 22 924 women), aged 35–74 years, selected from the main EPIC cohort.

Results:

A six- to sevenfold variation in total fish consumption exists in women and men, between the lowest consumption in Germany and the highest in Spain. Overall, white fish represented 49% and 45% of the intake of total fish in women and men, respectively, with the greatest consumption in centres in Spain and Greece and the least in the German and Dutch centres. Consumption of fatty fish reflected that of total fish. However, the greatest intake of very fatty fish was in the coastal areas of northern Europe (Denmark, Sweden and Norway) and in Germany. Consumption of fish products was greater in northern than in southern Europe, with white fish products predominating in centres in France, Italy, Spain, The Netherlands and Norway. Intake of roe and roe products was low. The highest consumption of crustacea was found in the French, Spanish and Italian centres. The number of fish types consumed was greater in southern than in northern Europe. The greatest variability in consumption by day of the week was found in the countries with the lowest fish intake.

Conclusions:

Throughout Europe, substantial geographic variation exists in total fish intake, fish sub-groups and the number of types consumed. Day-to-day variability in consumption is also high.