bluuebunny/crossref_metadata_2025 huggingface dataset:
Children raised in fatherless families from infancy: a follow‐up of children of lesbian and single heterosexual mothers at early adolescence
Authors: MacCallum Fiona , Golombok Susan
Published: January 2005

Background:  An increasing number of lesbian women and single heterosexual women are bringing up children with no male involvement. This study follows up to adolescence a sample of children raised in fatherless families from birth or early infancy.

Methods:  Twenty‐five lesbian mother families and 38 families headed by a single heterosexual mother were compared with 38 two‐parent heterosexual families. The quality of parenting by the mother, and the social and emotional development of the child, were assessed using standardised interview and questionnaire measures administered to mothers, children and teachers.

Results:  Children in fatherless families experienced more interaction with their mother, and perceived her as more available and dependable than their peers from father‐present homes. However, there were no group differences in maternal warmth towards the children. Mothers raising their child without a father reported more severe disputes with their child than did mothers in father‐present families. The children's social and emotional development was not negatively affected by the absence of a father, although boys in father‐absent families showed more feminine but no less masculine characteristics of gender role behaviour. No major differences in parenting or child development were identified between families headed by lesbian and single heterosexual mothers.

Conclusions:  The presence or absence of a father in the home from the outset does appear to have some influence on adolescents‘ relationships with their mothers. However, being without a resident father from infancy does not seem to have negative consequences for children. In addition, there is no evidence that the sexual orientation of the mother influences parent–child interaction or the socioemotional development of the child.
Associations among adolescent risk behaviours and self‐esteem in six domains
Authors: Wild Lauren G. , Flisher Alan J. , Bhana Arvin , Lombard Carl
Published: January 2005

Background:  This study investigated associations among adolescents’ self‐esteem in 6 domains (peers, school, family, sports/athletics, body image and global self‐worth) and risk behaviours related to substance use, bullying, suicidality and sexuality.

Method:  A multistage stratified sampling strategy was used to select a representative sample of 939 English‐, Afrikaans‐ and Xhosa‐speaking students in Grades 8 and 11 at public high schools in Cape Town, South Africa. Participants completed the multidimensional Self‐Esteem Questionnaire (SEQ; DuBois, Felner, Brand, Phillips, & Lease, 1996) and a self‐report questionnaire containing items about demographic characteristics and participation in a range of risk behaviours. It included questions about their use of tobacco, alcohol, cannabis, solvents and other substances, bullying, suicidal ideation and attempts, and risky sexual behaviour. Data was analysed using a series of logistic regression models, with the estimation of model parameters being done through generalised estimation equations.

Results:  Scores on each self‐esteem scale were significantly associated with at least one risk behaviour in male and female adolescents after controlling for the sampling strategy, grade and race. However, specific self‐esteem domains were differentially related to particular risk behaviours. After taking the correlations between the self‐esteem scales into account, low self‐esteem in the family and school contexts and high self‐esteem in the peer domain were significantly independently associated with multiple risk behaviours in adolescents of both sexes. Low body‐image self‐esteem and global self‐worth were also uniquely associated with risk behaviours in girls, but not in boys.

Conclusions:  Overall, the findings suggest that interventions that aim to protect adolescents from engaging in risk behaviours by increasing their self‐esteem are likely to be most effective and cost‐efficient if they are aimed at the family and school domains.
Being Gay
Authors: Stychin Carl F.
Published: January 2005

The article provides an overview of gay identity politics today. It begins with an introduction to the historical trajectory of the post-1945 period, and then turns to the challenges posed by queer politics and theory to gay identity politics. The related issue of the globalization of being gay is then considered, in terms of the universalizing of identity politics. Finally, the ramifications for gay identity politics of the political and legal recognition of same-sex relationships are discussed, leading to the obvious final question: whether being gay will continue to have a political logic in the years ahead.
Retrograde replacement of andalusite by Ca–Na mica in chloritoid‐bearing metapelites. PTX modelling of rocks with different Al content in the MnNCKFMASH system
Authors: MARTINEZ F. J. , RECHE J. , ARBOLEYA M. L. , JULIVERT M.
Published: January 2005

Andalusite porphyroblasts are totally pseudomorphosed by margarite–paragonite aggregates in aluminous pelites containing the peak mineral assemblage andalusite, chlorite, chloritoid, margarite, paragonite, quartz ± garnet, in a NW Iberia contact area. Equilibria at low P–T are investigated using new KFMASH and (mainly) MnCNKFMASH grids constructed with Thermocalc 3.21. P–T and T–X pseudosections with phase modal volume isopleths are constructed for compositions relatively richer and poorer in andalusite to model the assemblages in an andalusite‐bearing rock that contains a thin andalusite‐rich band (ARB) during retrogression. Their compositions, prior to retrogression, are used in the modelling, and have been retrieved by restoring the pseudomorph‐forming elements into the current‐depleted matrix, except for Al2O3 which is assumed to be immobile. Compositional differences between the thin band and the rest of the rock have not resulted in differences in andalusite porphyroblast retrogression. The absence of chloritoid resorbtion implies either a pressure increase at constant reacting‐system composition, or that its composition changed during retrogression at constant pressure, by becoming enriched in the progressively replaced andalusite porphyroblasts. T–X pseudosections at 1 kbar model this latter process using as end‐members in X, first, the restored original rock and ARB compositions, and, then the same process, taking into account the change in composition of both as retrogression proceeded. The MnNCKFMASH pseudosections of rocks with different Al contents facilitate making further deductions on the rock‐composition control of the resulting assemblages upon retrogression. Andalusite eventually disappears in relatively Al‐poor rocks, resulting, as in this study, in a rock formed by chloritoid–chlorite as the only FM minerals, plus margarite–paragonite pseudomorphs of andalusite. In rocks richer in Al, chlorite would progressively disappear and a kyanite/andalusite–chloritoid assemblage would eventually be stable at retrograde conditions. The Al‐silicate, stable during retrogression in Al‐rich rocks, indicates pressure conditions and hence the tectonic context under which retrogression took place.
Low‐P–high‐T metamorphism and the role of heat transport by melt migration in the Higo Metamorphic Complex, Kyushu, Japan
Authors: MIYAZAKI K.
Published: January 2005

This paper characterizes the metamorphic thermal structure of the Higo Metamorphic Complex (HMC) and presents the results of a numerical simulation of a geotherm with melt migration and solidification. Reconstruction of the geological and metamorphic structure shows that the HMC initially had a simple thermal structure where metamorphic temperatures and pressures increased towards apparent lower structural levels. Subsequently, this initial thermal structure has been collapsed by E–W and NNE–SSW trending high‐angle faults. Pressure and temperature conditions using the analysis of mineral assemblages and thermobarometry define a metamorphic field P–T array that may be divided into two segments: the array at apparent higher structural levels has a low‐dP/dT slope, whereas that at apparent lower structural levels has a high‐dP/dT slope. This composite array cannot be explained by heat conduction in subsolidus rocks alone. Migmatite is exposed pervasively at apparent lower structural levels, but large syn‐metamorphic plutons are absent at the levels exposed in the HMC. Transport and solidification of melt within migmatite is a potential mechanism to generate the composite array. Thermal modelling of a geotherm with melt migration and solidification shows that the composite thermal structure may be formed by a change of the dominant heat transfer from an advective regime to a conduction regime with decreasing depth. The model also predicts that strata beneath the crossing point will consist of high‐grade solid metamorphic rocks and solidified melt products, such as migmatite. This prediction is consistent with the observation that migmatite was associated with the very high‐dP/dT slope. The melt migration model is able to generate the very high‐dP/dT segment due to the high rate of heat transfer by advection.
Atom Collision-Induced Resistivity of Carbon Nanotubes
Authors: Romero Hugo E. , Bolton Kim , Rosén Arne , Eklund Peter C.
Published: January 2005

We report the observation of unusually strong and systematic changes in the electron transport in metallic single-walled carbon nanotubes that are undergoing collisions with inert gas atoms or small molecules. At fixed gas temperature and pressure, changes in the resistance and thermopower of thin films are observed that scale as roughly
M
1/3
, where
M
is the mass of the colliding gas species (He, Ar, Ne, Kr, Xe, CH
4
, and N
2
). Results of molecular dynamics simulations are also presented that show that the maximum deformation of the tube wall upon collision and the total energy transfer between the colliding atom and the nanotube also exhibit a roughly
M
1/3
dependence. It appears that the transient deformation (or dent) in the tube wall may provide a previously unknown scattering mechanism needed to explain the atom collision–induced changes in the electrical transport.
The Enigma of Prokaryotic Life in Deep Hypersaline Anoxic Basins
Authors: van der Wielen Paul W. J. J. , Bolhuis Henk , Borin Sara , Daffonchio Daniele , Corselli Cesare , Giuliano Laura , D'Auria Giuseppe , de Lange Gert J. , Huebner Andreas , Varnavas Sotirios P. , Thomson John , Tamburini Christian , Marty Danielle , McGenity Terry J. , Timmis Kenneth N. ,   BioDeep Scientific Party
Published: January 2005

Deep hypersaline anoxic basins in the Mediterranean Sea are a legacy of dissolution of ancient subterranean salt deposits from the Miocene period. Our study revealed that these hypersaline basins are not biogeochemical dead ends, but support in situ sulfate reduction, methanogenesis, and heterotrophic activity. A wide diversity of prokaryotes was observed, including a new, abundant, deeply branching order within the
Euryarchaeota
. Furthermore, we demonstrated the presence of a unique, metabolically active microbial community in the Discovery basin, which is one of the most extreme terrestrial saline environments known, as it is almost saturated with MgCl
2
(5 M).
Disulfide Isomerization After Membrane Release of Its SAR Domain Activates P1 Lysozyme
Authors: Xu Min , Arulandu Arockiasamy , Struck Douglas K. , Swanson Stephanie , Sacchettini James C. , Young Ry
Published: January 2005

The P1 lysozyme Lyz is secreted to the periplasm of
Escherichia coli
and accumulates in an inactive membrane-tethered form. Genetic and biochemical experiments show that, when released from the bilayer, Lyz is activated by an intramolecular thiol-disulfide isomerization, which requires a cysteine in its N-terminal SAR (signal-arrest-release) domain. Crystal structures confirm the alternative disulfide linkages in the two forms of Lyz and reveal dramatic conformational differences in the catalytic domain. Thus, the exported P1 endolysin is kept inactive by three levels of control—topological, conformational, and covalent—until its release from the membrane is triggered by the P1 holin.
A Field with a Life of Its Own
Authors: Bada Jeffrey L.
Published: January 2005

The Living Universe
NASA and the Development of Astrobiology.
By Steven J. Dick and James E. Strick
. Rutgers University Press, Piscataway, NJ, 2004. 288 pp. $49.95. ISBN 0-8135-3447-X.

Building on a review of the primary literature and oral history interviews, the authors chart the birth of exobiology and its subsequent transformation into the discipline of astrobiology.
Unveiling of Novel Radiations within
Trichodesmium
Cluster by
hetR
Gene Sequence Analysis
Authors: Lundgren Pernilla , Janson Sven , Jonasson Sara , Singer Alon , Bergman Birgitta
Published: January 2005

The filamentous nonheterocystous cyanobacterial genus
Katagnymene
is a common diazotrophic component of tropical and subtropical oceans. To assess the phylogenetic affiliation of this taxon, two partial 16S rRNA gene sequences and 25 partial
hetR
gene sequences originating from the genera
Katagnymene
and
Trichodesmium
collected from open, surface waters of the Atlantic, Indian, and Pacific oceans were compared. Single trichomes or colonies were identified morphologically by using light microscopy and then used directly as templates in
hetR
PCR analyses. In addition, three cultured strains, identified as
Katagnymene pelagica
,
Katagnymene spiralis
, and
Trichodesmium
sp., were examined. The data show that the genus
Katagnymene
is in the
Trichodesmium
cluster and that
K. pelagica
Lemmermann and
K. spiralis
Lemmermann are most likely one species, despite their different morphologies. Phylogenetic analyses also unveiled four distinct clusters in the
Trichodesmium
cluster, including one novel cluster. Our findings emphasize the conclusion that known morphological traits used to differentiate marine nonheterocystous cyanobacteria at the genus and species levels correlate poorly with genetic data, and a revision is therefore suggested.
Autotrophic Ammonia-Oxidizing Bacteria Contribute Minimally to Nitrification in a Nitrogen-Impacted Forested Ecosystem
Authors: Jordan Fiona L. , Cantera J. Jason L. , Fenn Mark E. , Stein Lisa Y.
Published: January 2005

Deposition rates of atmospheric nitrogenous pollutants to forests in the San Bernardino Mountains range east of Los Angeles, California, are the highest reported in North America. Acidic soils from the west end of the range are N-saturated and have elevated rates of N-mineralization, nitrification, and nitrate leaching. We assessed the impact of this heavy nitrogen load on autotrophic ammonia-oxidizing communities by investigating their composition, abundance, and activity. Analysis of 177 cloned β-
Proteobacteria
ammonia oxidizer 16S rRNA genes from highly to moderately N-impacted soils revealed similar levels of species composition; all of the soils supported the previously characterized
Nitrosospira
clusters 2, 3, and 4. Ammonia oxidizer abundance measured by quantitative PCR was also similar among the soils. However, rates of potential nitrification activity were greater for N-saturated soils than for soils collected from a less impacted site, but autotrophic (i.e., acetylene-sensitive) activity was low in all soils examined. N-saturated soils incubated for 30 days with ammonium accumulated additional soluble ammonium, whereas less-N-impacted soils had a net loss of ammonium. Lastly, nitrite production by cultivated
Nitrosospira multiformis
, an autotrophic ammonia-oxidizing bacterium adapted to relatively high ammonium concentrations, was significantly inhibited in pH-controlled slurries of sterilized soils amended with ammonium despite the maintenance of optimal ammonia-oxidizing conditions. Together, these results showed that factors other than autotrophic ammonia oxidizers contributed to high nitrification rates in these N-impacted forest soils and, unlike many other environments, differences in nitrogen content and soil pH did not favor particular autotrophic ammonia oxidizer groups.
Identification of Genes Differentially Expressed in Extraradical Mycelium and Ectomycorrhizal Roots during
Paxillus involutus-Betula pendula
Ectomycorrhizal Symbiosis
Authors: Morel Mélanie , Jacob Christophe , Kohler Annegret , Johansson Tomas , Martin Francis , Chalot Michel , Brun Annick
Published: January 2005

The development of ectomycorrhizal symbiosis leads to drastic changes in gene expression in both partners. However, little is known about the spatial regulation of symbiosis-regulated genes. Using cDNA array profiling, we compared the levels of expression of fungal genes corresponding to approximately 1,200 expressed sequenced tags in the ectomycorrhizal root tips (ECM) and the connected extraradical mycelium (EM) for the
Paxillus involutus
-
Betula pendula
ectomycorrhizal association grown on peat in a microcosm system. Sixty-five unique genes were found to be differentially expressed in these two fungal compartments. In ECM, a gene coding for a putative phosphatidylserine decarboxylase (Psd) was up-regulated by 24-fold, while genes coding for urea (Dur3) and spermine (Tpo3) transporters were up-regulated 4.1- and 6.2-fold in EM. Moreover, urea was the major nitrogen compound found in EM by gas chromatography-mass spectrometry analysis. These results suggest that (i) there is a spatial difference in the patterns of fungal gene expression between ECM and EM, (ii) urea and polyamine transporters could facilitate the translocation of nitrogen compounds within the EM network, and (iii) fungal Psd may contribute to membrane remodeling during ectomycorrhiza formation.
Genes Involved in Formation and Attachment of a Two-Carbon Chain as a Component of Eurekanate, a Branched-Chain Sugar Moiety of Avilamycin A
Authors: Treede Irina , Hauser Gerd , Mühlenweg Agnes , Hofmann Carsten , Schmidt Maraike , Weitnauer Gabriele , Glaser Steffen , Bechthold Andreas
Published: January 2005

Eurekanate belongs to the important class of branched-chain carbohydrates present in a wide variety of natural sources. It is a component of avilamycin A, a potent inhibitor of bacterial protein synthesis targeting the 50S ribosomal subunit. The present work provides experimental proof for the function of two genes of the avilamycin biosynthetic gene cluster,
aviB1
and
aviO2
, that are both involved in avilamycin structure modification. The functions of both genes were identified by gene inactivation experiments and nuclear magnetic resonance analyses of extracts produced by the mutants. We suggest that both AviO2 and AviB1 are involved in the biosynthesis of eurekanate within avilamycin biosynthesis. Moreover, two other genes (
aviO1
and
aviO3
) have been inactivated, resulting in a breakdown of avilamycin production in the mutants ITO1 and ITO3, which clearly shows the essential role of both enzymes in avilamycin biosynthesis. The exact functions of both
aviO1
and
aviO3
remained unknown.
Isolation and Characterization of a Native Composite Transposon, Tn
14751
, Carrying 17.4 Kilobases of
Corynebacterium glutamicum
Chromosomal DNA
Authors: Inui Masayuki , Tsuge Yota , Suzuki Nobuaki , Vertès Alain A. , Yukawa Hideaki
Published: January 2005

A native composite transposon was isolated from
Corynebacterium glutamicum
ATCC 14751. This transposon comprises two functional copies of a corynebacterial IS
31831
-like insertion sequence organized as converging terminal inverted repeats. This novel 20.3-kb element, Tn
14751
, carries 17.4 kb of
C. glutamicum
chromosomal DNA containing various genes, including genes involved in purine biosynthesis but not genes related to bacterial warfare, such as genes encoding mediators of antibiotic resistance or extracellular toxins. A derivative of this element carrying a kanamycin resistance cassette, minicomposite Tn
14751
, transposed into the genome of
C. glutamicum
at an efficiency of 1.8 × 10
2
transformants per μg of DNA. Random insertion of the Tn
14751
derivative carrying the kanamycin resistance cassette into the chromosome was verified by Southern hybridization. This work paves the way for realization of the concept of minimum genome factories in the search for metabolic engineering via genome-scale directed evolution through a combination of random and directed approaches.
Contribution of Folate Biosynthesis to
Ralstonia solanacearum
Proliferation in Intercellular Spaces
Authors: Shinohara Rena , Kanda Ayami , Ohnishi Kouhei , Kiba Akinori , Hikichi Yasufumi
Published: January 2005

The vigorous proliferation of
Ralstonia solanacearum
OE1-1 in host intercellular spaces after the invasion of host plants is necessary for the virulence of this bacterium. A folate auxotroph, RM, in which a mini-Tn
5
transposon was inserted into
pabB
encoding
para
-aminobenzoate synthase component I, lost its ability to vigorously proliferate in intercellular spaces along with its systemic infectivity and virulence after inoculation into roots and infiltration into leaves of tobacco plants. Complementation of RM with the
pabB
gene allowed the mutant to multiply in intercellular spaces and to cause disease. In tobacco plants that were pretreated with folate, RM was able to vigorously proliferate in the intercellular spaces and cause disease. Interestingly, when it was inoculated through cut stems, the mutant multiplied in the plants and was virulent. Moreover, the mutant multiplied well in stem fluids but not in intercellular fluids, suggesting that the folate concentration within intercellular spaces may be a limiting factor for bacterial proliferation. Therefore, folate biosynthesis contributes to the vigorous proliferation of bacteria in intercellular spaces and leads to systemic infectivity resulting in virulence.
Quantitative Real-Time Reverse Transcription-PCR Analysis of Deformed Wing Virus Infection in the Honeybee (
Apis mellifera
L.)
Authors: Chen Y. P. , Higgins J. A. , Feldlaufer M. F.
Published: January 2005

Deformed wing virus (DWV) can cause wing deformity and premature death in adult honeybees, although like many other bee viruses, DWV generally persists as a latent infection with no apparent symptoms. Using reverse transcription (RT)-PCR and Southern hybridization, we detected DWV in all life stages of honeybees, including adults with and without deformed wings. We also found DWV in the parasitic mite
Varroa destructor
, suggesting that this mite may be involved in the transmission of DWV. However, the detection of the virus in life stages not normally associated with mite parasitism (i.e., eggs and larvae) suggests that there are other modes of transmission. The levels of DWV in different life stages of bees were investigated by using TaqMan real-time quantitative RT-PCR. The amounts of virus varied significantly in these different stages, and the highest levels occurred in pupae and in adult worker bees with deformed wings. The variability in virus titer may reflect the different abilities of bees to resist DWV infection and replication. The epidemiology of DWV is discussed, and factors such as mite infestation, malnutrition, and climate are also considered.
Gene Structure and Transcriptional Organization of thednaKOperon ofBifidobacterium breveUCC 2003 and Application of the Operon in Bifidobacterial Tracing
Authors: Ventura Marco , Zink Ralf , Fitzgerald Gerald F. , van Sinderen Douwe
Published: January 2005

The incorporation and delivery of bifidobacterial strains as probiotic components in many food preparations expose these microorganisms to a multitude of environmental insults, including heat and osmotic stresses. We characterized thednaKgene region ofBifidobacterium breveUCC 2003. Sequence analysis of thednaKlocus revealed four genes with the organizationdnaK-grpE-dnaJ-ORF1, whose deduced protein products display significant similarity to corresponding chaperones found in other bacteria. Northern hybridization and real-time LightCycler PCR analysis revealed that the transcription of thednaKoperon was strongly induced by osmotic shock but was not induced significantly by heat stress. A 4.4-kb polycistronic mRNA, which represented the transcript of the completednaKgene region, was detected. Many other small transcripts, which were assumed to have resulted from intensive processing or degradation of this polycistronic mRNA, were identified. The transcription start site of thednaKoperon was determined by primer extension. Phylogenetic analysis of the available bifidobacterialgrpEanddnaKgenes suggested that the evolutionary development of these genes has been similar. The phylogeny derived from the various bifidobacterialgrpEanddnaKsequences is consistent with that derived from 16S rRNA. The use of these genes in bifidobacterial species as an alternative or complement to the 16S rRNA gene marker provides sequence signatures that allow a high level of discrimination between closely related species of this genus.
Chlorine Inactivation of Bacterial Bioterrorism Agents
Authors: Rose Laura J. , Rice Eugene W. , Jensen Bette , Murga Ricardo , Peterson Alicia , Donlan Rodney M. , Arduino Matthew J.
Published: January 2005

Seven species of bacterial select agents were tested for susceptibility to free available chlorine (FAC). Under test conditions, the FAC routinely maintained in potable water would be sufficient to reduce six species by 2 orders of magnitude within 10 min. Water contaminated with spores of
Bacillus anthracis
spores would require further treatment.
Mutation of a LysR-Type Regulator of Antifungal Activity Results in a Growth Advantage in Stationary Phase Phenotype in
Pseudomonas aureofaciens
PA147-2
Authors: Silby Mark W. , Giddens Stephen R. , Mahanty H. Khris
Published: January 2005

The growth advantage in stationary phase (GASP) phenotype was shown to be present in two mutants lacking the antifungal phenotype (Af
−
mutants) of
Pseudomonas aureofaciens
PA147-2. Complementation demonstrated a correlation between GASP and the antifungal defect in one strain but not in the second. Sequence analysis revealed the Af
−
GASP strain had a mutation in a gene (
finR
) encoding a LysR-type regulator. Antifungal-minus mutants arose in starved cultures, and those aged cultures had increased fitness. Taken together, the results show that there are at least two paths to the GASP phenotype in
P. aureofaciens
, one of which results in a concomitant loss of the antifungal phenotype.
Molecular Characterization of Resistance-Nodulation-Division Transporters from Solvent- and Drug-Resistant Bacteria in Petroleum-Contaminated Soil
Authors: Meguro Norika , Kodama Yumiko , Gallegos Maria-Trinidad , Watanabe Kazuya
Published: January 2005

PCR assays for analyzing resistance-nodulation-division transporters from solvent- and drug-resistant bacteria in soil were developed. Sequence analysis of amplicons showed that the PCR successfully retrieved transporter gene fragments from soil. Most of the genes retrieved from petroleum-contaminated soils formed a cluster (cluster PCS) that was distantly related to known transporter genes. Competitive PCR showed that the abundance of PCS genes is increased in petroleum-contaminated soil.
High-Level Overproduction of His-Tagged
Tth
DNA Polymerase in
Thermus thermophilus
Authors: Moreno Renata , Haro Amparo , Castellanos Angel , Berenguer José
Published: January 2005

A new plasmid for the overexpression of His-tagged thermozymes in
Thermus thermophilus
was developed. With this plasmid, soluble and active histidine-tagged DNA polymerase from
T. thermophilus
was overproduced in larger amounts in the thermophile than in
Escherichia coli.
The protein purified from the thermophile was active in PCR.
Heart and mind: (2) psychotropic and cardiovascular therapeutics
Authors: Shah S U , Iqbal Z , White A , White S
Published: January 2005

There is a plausible biological basis for the association between psychiatric morbidity and cardiovascular disease. Anxiety, panic disorder, and depression are common in patients with coronary heart disease and hypertension. Despite this evidence there is poor recognition of anxiety disorders and depression in primary care and hospital medical practice. Concern also surrounds the use of psychotropic drugs in patients with cardiovascular disease. In the first of the two articles on this subject, we highlighted the current evidence regarding the association between cardiovascular and psychotropic conditions. In this second article, we discuss the interaction of the drugs used in the management of these two varied but commonly coexistent group of diseases as well as their relative effects on either system. Finally, we summarise the data regarding the safe use of these medications based on the recommendations from the currently available evidence.
Reactivation of old scars: inevitably sarcoid
Authors: Sorabjee J S , Garje R
Published: January 2005

Reactivation of pre-existing scars, as a manifestation of cutaneous sarcoidosis, is uncommon and the clinical significance of this odd symptom often remains unrecognised. In the appropriate setting a skin biopsy may serve to establish the diagnosis of sarcoidosis and avoid more invasive attempts at obtaining tissue. The case of a 72 year old man with remote reactivation of multiple cutaneous scars associated with a febrile illness, malaise, and hilar adenopathy is reported. A scar biopsy revealed multiple non-caseating granulomas and established the diagnosis of sarcoidosis. A short course of steroids was successful in causing regression of symptoms and cutaneous inflammation. Regression of inflammation in the scar provides a simple way to monitor response to treatment in this multisystem disease.
Postprandial dysmetabolism and cardiovascular disease in type 2 diabetes
Authors: Tushuizen M E , Diamant M , Heine R J
Published: January 2005

The worldwide prevalence of type 2 diabetes mellitus has reached epidemic proportions. The so-called traditional risk factors cannot fully explain the excessive cardiovascular disease risk of type 2 diabetic patients. Numerous studies indicate that postprandial metabolic derangements, most notably hyperglycaemia and hypertriglyceridaemia, which are exaggerated and prolonged in type 2 diabetes, are important cardiovascular disease risk factors since they induce oxidative stress and endothelial dysfunctions. This review discusses the current evidence showing that postprandial dysmetabolism may indeed constitute an important cardiovascular disease risk factor as well as the mechanisms underlying this association. Finally, some possible therapeutic options and recommendations for future research are discussed.
Arrhythmias in an athlete: the effect of de-training
Authors: Obel O A , Davidson C
Published: January 2005

A 53 year old athlete with a history of severe palpitations and lightheadedness presented for a second opinion. He was found to exhibit very frequent atrial ectopy, frequent runs of symptomatic atrial tachyarrhythmia, and sinus bradycardia at rest. During exercise testing, his tachyarrhythmias increased in relation to the duration and intensity of exercise. A therapeutic trial of de-training was suggested. As a result, his symptoms completely resolved with a marked reduction in the frequency of atrial arrhythmia. Repeat exercise testing revealed an excellent exercise tolerance with no atrial ectopy. De-training should be considered when athletes present with arrhythmias.
Expression and effects of metabotropic CRF1and CRF2receptors in rat small intestine
Authors: Porcher Christophe , Juhem Aurélie , Peinnequin André , Sinniger Valérie , Bonaz Bruno
Published: January 2005

Corticotropin-releasing factor (CRF)-like peptides mediate their effects via two receptor subtypes, CRF1and CRF2; these receptors have functional implication in the motility of the stomach and colon in rats. We evaluated expression and functions of CRF1and CRF2receptors in the rat small intestine (i.e., duodenum and ileum). CRF1–2-like immunoreactivity (CRF1–2-LI) was localized in fibers and neurons of the myenteric and submucosal ganglia. CRF1–2-LI was found in nerve fibers of the longitudinal and circular muscle layers, in the mucosa, and in mucosal cells. Quantitative RT-PCR showed a stronger expression of CRF2than CRF1in the ileum, whereas CRF1expression was higher than CRF2expression in the duodenum. Functional studies showed that CRF-like peptides increased duodenal phasic contractions and reduced ileal contractions. CRF1antagonists (CP-154,526 and SSR125543Q) blocked CRF-like peptide-induced activation of duodenal motility but did not block CRF-like peptide-induced inhibition of ileal motility. In contrast, a CRF2inhibitor (astressin2-B) blocked the effects of CRF-like peptides on ileal muscle contractions but did not influence CRF-like peptide-induced activation of duodenal motility. These results demonstrate the presence of CRF1–2in the intestine and demonstrate that, in vitro, CRF-like peptides stimulate the contractile activity of the duodenum through CRF1receptor while inhibiting phasic contractions of the ileum through CRF2receptor. These results strongly suggest that CRF-like peptides play a major role in the regulatory mechanisms that underlie the neural control of small intestinal motility through CRF receptors.
Cardiac myocytes control release of endothelin-1 in coronary vasculature
Authors: Merkus Daphne , Brzezinska Anna K. , Zhang Cuihua , Saito Shuichi , Chilian William M.
Published: January 2005

α-Adrenergic vasoconstriction in the coronary circulation is mediated through α-adrenoceptors on cardiac myocytes and subsequent release of endothelin, a very potent, long-lasting vasoconstrictor. Recent studies found that adult cardiac myocytes do not express the preproendothelin gene. Thus we hypothesized that α-adrenoceptor stimulation on the cardiac myocytes results in the production of an endothelin-releasing factor, which stimulates the coronary vasculature to produce endothelin. We tested this hypothesis by using an in vitro model in which isolated adult rat cardiac myocytes can be stimulated with an α-adrenoceptor agonist (phenylephrine). Their bathing fluid is then transferred to isolated coronary arterioles, and vasoactive responses are measured. To identify the source of endothelin, the endothelin-converting enzyme inhibitor phosphoramidon was added to either the myocytes or the isolated arterioles. Phenylephrine enhanced the vasoconstrictor properties of the myocyte bathing fluid. Administration of phosphoramidon (in either the presence or the absence of phenylephrine) to the myocytes had no effect on the vasoactive properties of the bathing fluid. In contrast, administration of phosphoramidon to the isolated arteriole before administration of the bathing fluid converted vasoconstriction to vasodilation, similar to the effect of the endothelin A receptor antagonist JKC-301, indicating that the endothelin is indeed produced by the coronary vasculature. Administration of the angiotensin type 1 receptor antagonist losartan to the vessel bath enhanced vasodilation to the bathing fluid of the phenylephrine-treated but not control myocytes. In conclusion, during α-adrenergic activation cardiac myocytes release a factor, probably angiotensin II, that stimulates the vascular production of endothelin. Although the physiological implications of this mechanism are not obvious, this may represent a protective mechanism that integrates neuronal vasoconstrictor mechanisms with myocardial metabolism, which minimizes periods of both coronary underperfusion and overperfusion.
Cocaine and catecholamines enhance inflammatory cell retention in the coronary circulation of mice by upregulation of adhesion molecules
Authors: Chen Yu , Ke Qingen , Xiao Yong-Fu , Wu Guifu , Kaplan Emel , Hampton Thomas G. , Malek Sohail , Min Jiang-Yong , Amende Ivo , Morgan James P.
Published: January 2005

Cocaine treatment of mice with viral myocarditis significantly increases neutrophil infiltration into the myocardium and exacerbates the inflammatory response. The mechanisms of these effects are unknown; however, it may be that cocaine increases circulating catecholamines and consequently increases inflammatory cell adhesion to the coronary endothelium. Here, we examined the hypothesis that cocaine enhances inflammatory cell infiltration via catecholamine-induced upregulation of cell adhesion molecule (CAM) expression in adult BALB/c mouse hearts. Intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), endothelial leukocyte adhesion molecule-1 (E-selectin), and leukocyte adhesion molecule-1 (L-selectin) were detected by gene array analysis, RT-PCR, Western blotting, and immunohistochemical staining. CAMs were significantly upregulated in cocaine-treated mouse hearts. β-Adrenergic stimulation with epinephrine also upregulated CAM expression, confirming the effects obtained with cocaine. β-Adrenergic blockade with propranolol inhibited epinephrine-induced CAM expression. In hearts infused with polymorphonuclear neutrophils (PMN), an increased adhesion of PMN to the coronary endothelium was observed in cocaine-treated and epinephrine-treated mouse hearts compared with control hearts. Blocking antibodies against ICAM-1, E-selectin, and L-selectin significantly inhibited epinephrine-enhanced PMN adhesion, whereas anti-VCAM-1 had lesser effects. Our findings suggest that cocaine-induced neutrophil infiltration is mediated by β-adrenergic stimulation through upregulation of CAM expression, which enhances PMN adhesion. Conversely, β-adrenergic blockade with propranolol inhibits the effects of cocaine and epinephrine on CAM expression and decreases PMN adhesion to the coronary endothelium. These observations may be of significance for the development of preventative and therapeutic approaches to patients with cocaine- or catecholamine-induced myocarditis.
Muscle capillary blood flow kinetics estimated from pulmonary O2 uptake and near-infrared spectroscopy
Authors: Ferreira Leonardo F. , Townsend Dana K. , Lutjemeier Barbara J. , Barstow Thomas J.
Published: January 2005

The near-infrared spectroscopy (NIRS) signal (deoxyhemoglobin concentration; [HHb]) reflects the dynamic balance between muscle capillary blood flow (Q̇cap) and muscle O2 uptake (V̇o2m) in the microcirculation. The purposes of the present study were to estimate the time course of Q̇cap from the kinetics of the primary component of pulmonary O2 uptake (V̇o2p) and [HHb] throughout exercise, and compare the Q̇cap kinetics with the V̇o2p kinetics. Nine subjects performed moderate- (M; below lactate threshold) and heavy-intensity (H, above lactate threshold) constant-work-rate tests. V̇o2p (l/min) was measured breath by breath, and [HHb] (μM) was measured by NIRS during the tests. The time course of Q̇cap was estimated from the rearrangement of the Fick equation [Q̇cap = V̇o2m/(a-v)O2, where (a-v)O2 is arteriovenous O2 difference] using V̇o2p (primary component) and [HHb] as proxies of V̇o2m and (a-v)O2, respectively. The kinetics of [HHb] [time constant (τ) + time delay [HHb]; M = 17.8 ± 2.3 s and H = 13.7 ± 1.4 s] were significantly ( P < 0.001) faster than the kinetics of V̇o2 [τ of primary component (τP); M = 25.5 ± 8.8 s and H = 25.6 ± 7.2 s] and Q̇cap [mean response time (MRT); M = 25.4 ± 9.1 s and H = 25.7 ± 7.7 s]. However, there was no significant difference between MRT of Q̇cap and τP-V̇o2 for both intensities ( P = 0.99), and these parameters were significantly correlated (M and H; r = 0.99; P < 0.001). In conclusion, we have proposed a new method to noninvasively approximate Q̇cap kinetics in humans during exercise. The resulting overall Q̇cap kinetics appeared to be tightly coupled to the temporal profile of V̇o2m.
Antiprothrombin antibodies detected in two different assay systems
Authors: Atsumi Tatsuya , Koike Takao , Hughes Graham R. V. , Khamashta Munther A. , Bertolaccini Maria Laura
Published: January 2005

We evaluated the clinical significance of aPT and aPS-PT by testing for the presence of these antibodies in 212 SLE patients and in 100 healthy individuals. Results show that anti-prothrombin antibodies were found in 47% of the patients (aPT in 31% and aPS-PT in 31%). Their presence did not correlate with that of aCL, anti-β 2GPI, LA and/or anti-protein S. IgG but not IgM aPT were more frequently found in patients with thrombosis than in those without. IgG and IgM aPS-PT were also more frequent in patients with thrombosis (venous and/or arterial) than in those without. Levels of IgG aPT and IgG and IgM aPS-PT were higher in patients with thrombosis than in those without. Although aPT and aPS-PT were more frequently found in women with adverse obstetric history than in those without, the differences were not statistically significant. More significantly, 48% of the patients with aPL-related clinical features who were negative for standard tests had antiprothrombin antibodies. We can conclude that aPT and aPS-PT are frequently found in SLE. Their presence is associated with thrombosis, making these antibodies potential markers for the APS. Testing for these antibodies could be of clinical benefit in patients who are negative for the routinely used tests.
Myocardial extra-cellular matrix and its regulation by metalloproteinases and their inhibitors
Authors: Kassiri Zamaneh , Khokha Rama
Published: January 2005

Cardiovascular disease poses a major health care burden in the Western world. Following myocardial injuries, ventricular remodelling and dysfunction ensue, which can eventually culminate in heart failure. An important event in left ventricular (LV) remodelling is alteration of the extracellular matrix (ECM) integrity, the structural network that interconnects the myocardial components. The critical role of ECM remodelling in cardiac dilation and heart failure was recognized more than a decade ago, and the molecular factors responsible for this process are now being explored. Abnormal ECM turnover is primarily brought about by an imbalance in the activity of matrix metalloproteinases (MMPs) that degrade ECM components, and their endogenous inhibitors, tissue inhibitors of metalloproteinases (TIMPs). Here we provide an overview of composition of the cardiac ECM, and alterations in ECM regulatory proteins, MMPs and TIMPs, in human heart disease. We also discuss the role of TIMPs, MMPs, and a disintegrin and metalloproteinase (ADAMs) enzymes in cardiac development and function as learned through genetically altered mouse models.
The organomercurial 4-aminophenylmercuric acetate, independent of matrix metalloproteinases, induces dose-dependent activation/ inhibition of platelet aggregation
Authors: Rosenfeldt Mathias T. , Valentino Michael , Labruzzo Salvatore , Scudder Lesley , Pavlaki Maria , Cao Jian , Vacirca Jeffrey , Bahou Wadie F. , Zucker Stanley
Published: January 2005

Matrix metalloproteinases (MMPs) play an important role in many biological and pathological processes including tissue remodeling, wound healing, inflammation, atherosclerosis, and cancer. Numerous publications have supported the concept that activated MMP-2 enhances agonist-induced platelet aggregation and activated MMP-9 inhibits platelet aggregation. In this study, we demonstrated that the organomercurial compound, 4-aminophenyl mercuric acetate (APMA), which is routinely employed to activate latent MMPs at a concentration of 1000 μ M, induces platelet aggregation at low concentration (5 μ M) and inhibits agonist-induced platelet aggregation at concentrations ≥ 50 μ M. Activated MMP-2, MMP-1, and MMP-9, following removal of APMA by ultrafiltration through an anisotropic membrane, exert no independent effect on platelet aggregation. Acetylsalicylic acid and BAPTA inhibited APMA-induced platelet aggregation indicating that the APMA mediated pathway of platelet activation is dependent upon thromboxane and calcium signaling. Zinc chelation with 1,10-phenanthroline, which inhibits zincdependent proteins including metalloproteinases, also abrogated platelet functional responses to APMA. Additional studies will be required to clarify the mechanism of the biphasic effect of APMA on platelet aggregation.
Soluble CD40L in peripheral artery disease
Authors: Tan Kiat , Tayebjee Muzahir , Davagnanam Indran , Moss Mark , Lip Gregory , Blann Andrew
Published: January 2005

Although soluble CD40L (sCD40L, possibly derived from platelets and pro-inflammatory in vitro) may be implicated in thrombosis and haemostasis, there are little data in peripheral artery disease (PAD). We hypothesised the following: (a) that sCD40L relates to the clinical severity of PAD; and (b) that peripheral artery angioplasty acutely raises sCD40L levels. sCD40L was compared to established platelet markers soluble P selectin, platelet microparticles and platelet surface expression of CD62 and CD63. We recruited 36 healthy controls, 33 patients with intermittent claudication (IC), and 33 with symptomatically more severe critical limb is chaemia (CLI), measuring plasma markers by ELISA and membrane markers by flow cytometry. Eleven patients with CLI subsequently underwent peripheral artery angioplasty: blood was taken before and 10 minutes after the intervention. Results show that sCD40L was raised in IC at median 68 (IQR 28–333) pg/ml and in CLI at 64 (34–282) pg/mL compared to 35 (IQR 28–55) pg/ml in the healthy controls (p=0.009). Levels were no different between IC and CLI. The same distribution pattern was present for soluble P selectin, %platelets CD62+ve and CD63+ve. sCD40L failed to correlate significantly with ABPI (p=0.264), unlike %platelets CD62+ve (p=0.0032) and CD63+ve (p=0.009). Pre-angioplasty sCD40L level of 72 (35–610) ng/ml rose to 100 ng/ml (IQR=60–237)(p=0.018) post–angioplasty. Plasma sCD40L, in addition to other platelet indices, is raised in peripheral atherosclerosis and is increased by peripheral artery angioplasty, although levels seem unrelated to clinical severity. Failure to correlate with other markers suggest the platelet may not be the sole source of sCD40L, and that other cells may contribute to plasma levels.
Hepatocyte Growth Factor Suppresses Vascular Endothelial Growth Factor-Induced Expression of Endothelial ICAM-1 and VCAM-1 by Inhibiting the Nuclear Factor-κB Pathway
Authors: Min Jeong-Ki , Lee Young-Mi , Kim Jeong Hun , Kim Young-Myeong , Kim Sung Wan , Lee Soo-Young , Gho Yong Song , Oh Goo Taeg , Kwon Young-Guen
Published: January 2005

Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are potent angiogenic factors that have been used clinically to induce angiogenesis. However, concerns have been raised about VEGF because of its proinflammatory actions, which include enhancing the adhesion of leukocytes to endothelial cells. We have examined the possible antiinflammatory effects of HGF on the vasculature. HGF, unlike VEGF, did not alter leukocyte adhesion to endothelial cells. Instead it inhibited VEGF-induced leukocyte-endothelial cell interactions and the endothelial expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In a skin inflammation model, VEGF-treated mice showed a significant increase of leukocytes infiltrated or adherent to the luminal surface of blood vessels, as compared with vehicle- or HGF-treated mice. The VEGF effect was markedly suppressed by coadministration of HGF. RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. Furthermore, these inhibitory effects coincided with suppression of IκB kinase activity, and this in turn prevented the activation of the inflammatory transcription factor NF-κB. Taken together, our results demonstrate that HGF suppresses VEGF-induced inflammation presumably by inhibiting the endothelial NF-κB pathway. This suggests that combined treatment with HGF and VEGF could be superior to treatment with either factor alone for enhancing therapeutic angiogenesis while avoiding inflammation.