bluuebunny/crossref_metadata_2025 huggingface dataset:
The green tea polyphenol (−)‐epigallocatechin gallate and green tea can protect human cellular DNA from ultraviolet and visible radiation‐induced damage
Authors: Morley Nick , Clifford Tim , Salter Leo , Campbell Sandra , Gould David , Curnow Alison
Published: December 2004

Background: Antioxidant compounds in green tea may be able to protect against skin carcinogenesis and it is of interest to investigate the mechanisms involved. A study was therefore conducted to determine whether the isolated green tea polyphenol (−)‐epigallocatechin gallate (EGCG) could prevent ultraviolet radiation (UVR)‐induced DNA damage in cultured human cells. This work was then extended to investigate whether drinking green tea could afford any UVR protection to human peripheral blood cells collected after tea ingestion.

Methods: The alkaline comet assay was used to compare the DNA damage induced by UVR in cultured human cells with and without the presence of EGCG. The same assay technique was then employed to assess UVR‐induced DNA damage in peripheral leucocytes isolated from 10 adult human volunteers before and after drinking 540 ml of green tea.

Results: Initial trials found that EGCG afforded concentration‐dependent photoprotection to cultured human cells with a maximal activity at a culture concentration of 250 μM. The cells types tested (lung fibroblasts, skin fibroblasts and epidermal keratinocytes) demonstrated varying susceptibility to the UVR insult provided. The in vivo trials of green tea also demonstrated a photoprotective effect, with samples of peripheral blood cells taken after green tea consumption showing lower levels of DNA damage than those taken prior to ingestion when exposed to 12 min ultraviolet A (UVA) radiation.

Conclusion: The studies showed that green tea and/or some constituents can offer some protection against UV‐induced DNA damage in human cell cultures and also in human peripheral blood samples taken post‐tea ingestion.
Ultraviolet‐A1 (340–400 nm)‐mediated receptor and cytokine changes of transformed lymphocytes
Authors: Godar Dianne E. , Lucas Anne D.
Published: December 2004

Background: Ultraviolet‐A1 (340–400 nm) (UVA1) radiation causes singlet‐oxygen damage that depolarizes mitochondrial membranes triggering immediate apoptosis (T≤4 h), while it also causes oxidative damage to DNA inducing delayed apoptosis (T≥24 h). In this study, we examined some potential therapeutic endpoints associated with UVA1‐mediated immediate and delayed apoptosis, such as receptor and cytokine changes.

Methods: We quantified the number of membrane‐bound CD3 receptors on transformed T lymphocytes (Jurkat) and the number of membrane‐bound CD19 receptors on transformed B lymphocytes (Daudi) using flow cytometry. We also quantified the release of the cytokines interferon γ (IFN‐γ) and interleukin‐2 (IL‐2) using enzyme‐linked immunosorbent assays.

Results: Out of the entire population of cells, only the apoptotic Daudi cells immediately decreased CD19 expression via capping, while only the apoptotic Jurkat cells increased CD3 receptor expression 24 h post‐exposure. Both receptor changes occurred in a UVA1 dose‐dependent manner. We also examined other T‐cell receptors, such as CD4, CD25, and CD69, but they did not change for up to 24 h following exposure. During UVA1‐triggered immediate apoptosis of Jurkat T cells, IFN‐γ levels increased in a dose‐dependent manner at 4 h, but returned to baseline levels at 24 h post‐exposure, whereas, there was no significant change in IL‐2 at 4 or 24 h.

Conclusion: Thus, UVA1‐triggered immediate apoptosis causes a rapid decrease in the number of CD19 receptors on Daudi B cells and release of IFN‐γ from Jurkat T cells at 4 h, and UVA1‐mediated delayed apoptosis causes an increase in the number of CD3 receptors on Jurkat T cells.
Plateau potentials and membrane oscillations in parasympathetic preganglionic neurones and intermediolateral neurones in the rat lumbosacral spinal cord
Authors: Derjean D. , Bertrand S. , Nagy F. , Shefchyk S. J.
Published: December 2004

Whole‐cell patch recordings were made from parasympathetic preganglionic neurones (P‐PGNs) and unidentified intermediolateral (IML) neurones in thick slices of the lower lumbar and sacral spinal cord of 14‐ to 21‐day‐old rats. The P‐PGNs and IML neurones examined were similar in terms of soma sizes, input resistance and capacitance, and displayed a sag conductance as well as rebound firing. In the absence of drugs, the neurones responded with either tonic or adapting firing to depolarizing current steps. However, in the presence of the group I metabotropic glutamate receptor agonist (RS)‐3,5‐dihydroxyphenylglycine (DHPG), almost half of the neurones displayed accelerating firing rates during the constant current injection, followed by a sustained after‐discharge. In the presence of TTX, plateau potentials were observed. The firing changes and plateaux were blocked by nifedipine, an L‐type Ca2+ channel blocker, and (S)‐(−)‐Bay K8644 was able to produce these firing changes and plateaux in the absence of DHPG, demonstrating the involvement of an L‐type Ca2+ conductance. Ca2+‐activated nonspecific cationic conductances also appear to contribute to the firing changes. A few neurones displayed membrane oscillations and burst firing in the presence of DHPG. The results suggest that the firing characteristics of both P‐PGNs and other neurones likely to be involved in caudal spinal reflex control are not static but, rather, quite dynamic and under metabotropic glutamate receptor modulatory control. Such changes in firing patterns may be involved in normal pelvic parasympathetic reflex function during micturition, defaecation and sexual reflexes, and may contribute to the abnormal output patterns seen with loss of descending brainstem input and visceral or perineal sensory disturbances.
Microelectrode array recordings of cultured hippocampal networks reveal a simple model for transcription and protein synthesis‐dependent plasticity
Authors: Arnold Fiona J. L. , Hofmann Frank , Bengtson C. Peter , Wittmann Malte , Vanhoutte Peter , Bading Hilmar
Published: December 2004

A simplified cell culture system was developed to study neuronal plasticity. As changes in synaptic strength may alter network activity patterns, we grew hippocampal neurones on a microelectrode array (MEA) and monitored their collective behaviour with 60 electrodes simultaneously. We found that exposure of the network for 15 min to the GABAA receptor antagonist bicuculline induced an increase in synaptic efficacy at excitatory synapses that was associated with an increase in the frequency of miniature AMPA receptor‐mediated EPSCs and a change in network activity from uncoordinated firing of neurones (lacking any recognizable pattern) to a highly organized, periodic and synchronous burst pattern. Induction of recurrent synchronous bursting was dependent on NMDA receptor activation and required extracellular signal‐regulated kinase (ERK)1/2 signalling and translation of pre‐existing mRNAs. Once induced, the burst pattern persisted for several days; its maintenance phase (> 4 h) was dependent on gene transcription taking place in a critical period of 120 min following induction. Thus, cultured hippocampal neurones display a simple, transcription and protein synthesis‐dependent form of plasticity. The non‐invasive nature of MEA recordings provides a significant advantage over traditional assays for synaptic connectivity (i.e. long‐term potentiation in brain slices) and facilitates the search for activity‐regulated genes critical for late‐phase plasticity.
Length‐dependent filament formation assessed from birefringence increases during activation of porcine tracheal muscle
Authors: Smolensky Alexander V. , Ragozzino Joseph , Gilbert Susan H. , Seow Chun Y. , Ford Lincoln E.
Published: December 2004

Birefringence and force produced by pig tracheal smooth muscles were recorded every 100 ms during electrically stimulated tetani at muscle lengths that varied 1.5‐fold and at the peak of acetylcholine contractures at the same lengths. Isometric force was nearly the same at all lengths. Resting birefringence at the longest length was 30% greater than that at the shortest length. During tetani, birefringence increased with approximately the same time course as force, rising by 20% at the shortest length and 9% at the longest length, and continued to increase by an additional 0.5–1.5% of the resting value for 2–8 s after stimulation ended and force began to fall. This late increase was greatest and more sustained at longer lengths. During contractures, birefringence increased by 25 and 18% at the shortest and longest lengths, respectively. Comparison of these results with our published thick‐filament densities suggests that thick‐filament density increased by about 80, 72 and 50% during contractures at the short, intermediate and long lengths, and that ∼35% of birefringence in the resting muscle at the longest length was not due to thick filaments. These findings support the hypotheses that tracheal smooth muscle adapts to longer lengths by increasing thick‐filament mass and that myosin thick filaments are evanescent, dissociating partially during relaxation and reforming upon activation. The results further suggest that thick‐filament formation is sufficiently rapid to account for the velocity slowing and some of the force increase observed during the rise of activation of tracheal smooth muscle.
Focus Issue: Cell Signaling—Making New Connections
Authors: Gough Nancy R. , Adler Elizabeth M. , Ray L. Bryan
Published: December 2004

The 2004 annual Cell Signaling issue in
Science
and
Science's STKE
brings new pathways to the Connections Maps cell signaling database, as well as highlights updates to pathways featured previously. The new pathways reveal core signaling modules common to yeast, plants, and animals. Opportunities for using the Connections Maps database expand with the availability of an XML-formatted version of the data and the addition of The Blueprint Initiative as a new technical provider for the cell signaling database.
Positional Signaling Mediated by a Receptor-like Kinase in
Arabidopsis
Authors: Kwak Su-Hwan , Shen Ronglai , Schiefelbein John
Published: December 2004

The position-dependent specification of root epidermal cells in
Arabidopsis
provides an elegant paradigm for cell patterning during development. Here, we describe a new gene,
SCRAMBLED
(
SCM
), required for cells to appropriately interpret their location within the developing root epidermis.
SCM
encodes a receptor-like kinase protein with a predicted extracellular domain of six leucine-rich repeats and an intracellular serine-threonine kinase domain. SCM regulates the expression of the
GLABRA2, CAPRICE, WEREWOLF
, and
ENHANCER OF GLABRA3
transcription factor genes that define the cell fates. Further, the
SCM
gene is expressed throughout the developing root. Therefore, SCM likely enables developing epidermal cells to detect positional cues and establish an appropriate cell-type pattern.
Attraction or Repulsion: A Matter of Individual Taste?
Authors: Wells Alan , Lillien Laura
Published: December 2004

Cell migration along the correct paths is critical to normal organogenesis and tissue repair, and goes awry in tumor dissemination. Understanding the molecular cues that control such migration would provide opportunities to control these events. Recent findings in
Drosophila
highlight the role of the epidermal growth factor receptor (EGFR) in chemotaxis and pathfinding during development. These studies, and others performed in vertebrates, support a central role for EGFR-mediated chemotaxis. However, the signal or signals that then enable cells to further migrate independently of this chemotactic effect are not known. Three possible scenarios are discussed: that EGFR signaling sensitizes cells to new cues, that EGFR signaling is altered so that the cell responds predominantly to other motility signals that are now "unblinded," and that EGFR signaling still provides the motile signal but in a chemokinetic manner with matrix components providing the directionality. There are precedents for all three scenarios, but which one proves true will define the window of opportunity for regulating cell migration.
The Strength of Indecisiveness: Oscillatory Behavior for Better Cell Fate Determination
Authors: Lahav Galit
Published: December 2004

Oscillatory behavior is very common in many cellular responses. Recently, two pathways involved in response to cell stress, the p53 and nuclear factor kappa B signaling pathways, have been found to show oscillatory behavior. At first sight, there would seem to be no reason for signaling pathways of this type to require oscillations. Recent single-cell studies indicate that oscillatory behavior may be used to allow repeated testing for the continued existence of a signal. I argue that oscillations increase cellular response sensitivity and flexibility by allowing the cell to integrate the results of many periodical evaluations of the signal before making an eventual decision about cell fate, thus reducing the risk of premature commitment.
Oxygen-dependent PAF receptor binding and intracellular signaling in ovine fetal pulmonary vascular smooth muscle
Authors: Ibe Basil O. , Portugal Ada M. , Chaturvedi Shiva , Raj J. Usha
Published: December 2004

Circulating levels of platelet-activating factor (PAF) are high in the fetus, and PAF is active in maintaining high PVR in fetal hypoxia (Ibe BO, Hibler S, Raj J. J Appl Physiol 85: 1079–1085, 1998). PAF synthesis by fetal pulmonary vascular smooth muscle cells (PVSMC) is high in hypoxia, but how oxygen tension affects PAF receptor (PAF-r) binding in PVSMC is not known. We studied the effect of oxygen tension on PAF-r binding and signaling in fetal PVSMC. PAF binding was saturable. PAF-r density (Bmax: fmol/106cells; means ± SE, n = 6), 25.2 ± 0.77 during hypoxia (Po2<40 Torr), was higher than 13.9 ± 0.44 during normoxia (Po2∼100 Torr). Kdwas twofold lower in hypoxia than normoxia. PAF-r protein expression, 35–40% greater in hypoxia, was inhibited by cycloheximide, a protein synthesis inhibitor, suggesting translational regulation. IP3release, an index of PAF-r-mediated cell signaling, was greater in hypoxia (EC50: hypoxia, 2.94 ± 0.61; normoxia, 5.85 ± 0.51 nM). Exogenous PAF induced 50–90% greater intracellular calcium flux in cells during hypoxia, indicating hypoxia augments PAF-r-mediated cell signaling. PAF-r phosphorylation, with or without 5 nM PAF, was 40% greater in hypoxia. These data show 1) hypoxia upregulates PAF-r binding, PAF-r phosphorylation, and PAF-r-mediated intracellular signaling, evidenced by augmented IP3production and intracellular Ca2+flux; and 2) hypoxia-induced PAF-r phosphorylation results in activation of PAF-r-mediated signal transduction. The data suggest the fetal hypoxic environment facilitates PAF-r binding and signaling, thereby promoting PAF-mediated pulmonary vasoconstriction and maintenance of high PVR in utero.
Heart rate deflection point as a strategy to defend stroke volume during incremental exercise
Authors: Lepretre Pierre-Marie , Foster Carl , Koralsztein Jean-Pierre , Billat Veronique L.
Published: December 2004

The purpose of this study was to examine whether the heart rate (HR) deflection point (HRDP) in the HR-power relationship is concomitant with the maximal stroke volume (SVmax) value achievement in endurance-trained subjects. Twenty-two international male cyclists (30.3 ± 7.3 yr, 179.7 ± 7.2 cm, 71.3 ± 5.5 kg) undertook a graded cycling exercise (50 W every 3 min) in the upright position. Thoracic impedance was used to measure continuously the HR and stroke volume (SV) values. The HRDP was estimated by the third-order curvilinear regression method. As a result, 72.7% of the subjects (HRDP group, n = 16) presented a break point in their HR-work rate curve at 89.9 ± 2.8% of their maximal HR value. The SV value increased until 78.0 ± 9.3% of the power associated with maximal O2 uptake (V̇o2 max) in the HRDP group, whereas it increased until 94.4 ± 8.6% of the power associated with V̇o2 max in six other subjects (no-HRDP group, P = 0.004). Neither SVmax (ml/beat or ml·beat−1·m−2) nor V̇o2 max (ml/min or ml·kg−1·min−1) were different between both groups. However, SV significantly decreased before exhaustion in the HRDP group (153 ± 44 vs. 144 ± 40 ml/beat, P = 0.005). In the HRDP group, 62% of the variance in the power associated with the SVmax could also be predicted by the power output at which HRDP appeared. In conclusion, in well-trained subjects, the power associated with the SVmax-HRDP relationship supposed that the HR deflection coincided with the optimal cardiac work for which SVmax was attained.
Continuous Ambulatory Peritoneal Dialysis in Familial Mediterranean Fever Amyloidosis Patients with End-Stage Renal Failure: A Single-Centre Experience from Turkey
Authors: Altıparmak Mehmet Rıza , Pamuk Ömer Nuri , Ataman Rezzan , Serdengeçti Kamil
Published: December 2004

Background/Aims: Familial Mediterranean fever (FMF) is an autosomal recessive disease characterised by recurrent fever attacks and polyserositis which may lead to the development of AA amyloidosis and end-stage renal disease (ESRD). In this study, we aimed to evaluate the efficacy of continuous ambulatory peritoneal dialysis (CAPD) in FMF-amyloidosis patients with ESRD. Methods: Forty age- and sex-matched patients undergoing CAPD at our centre between 1996 and 2002 were included in the study. Of these, 10 had FMF-amyloidosis, 10 had diabetes mellitus (DM), 10 had chronic glomerulonephritis (CGN) and 10 had chronic interstitial nephritis (CIN). Efficiency of CAPD, development of complications, presence of other diseases and survival were compared. Results: With the onset of ESRD, the frequency of FMF peritonitis attacks decreased, with less attacks occurring during CAPD in FMF-amyloidosis patients (p < 0.05). There was no significant difference between the FMF-amyloidosis group and other groups in terms of efficiency of CAPD, peritoneal function, complications and survival. DM patients had a shorter survival period compared with CGN and CIN patients (p < 0.05), but there was no survival difference between FMF-amyloidosis patients and other groups (p > 0.05). Conclusions: We conclude that CAPD is an effective and safe renal replacement therapy for FMF-amyloidosis patients with ESRD.
Iron Dextran Causes Renal Iron Deposition but Not Renal Dysfunction in Angiotensin II-Treated and Untreated Rats
Authors: Ishizaka Nobukazu , Saito Kan , Noiri Eisei , Sata Masataka , Mori Ichiro , Ohno Minoru , Nagai Ryozo
Published: December 2004

Background: Angiotensin II infusion into rats causes iron deposition in the kidney, which may augment the pro-proteinuric effects of this octapeptide. We have investigated whether administration of iron mimics the renal damage induced by angiotensin II. Methods: Rats were treated with iron dextran at a total dose of 960 mg/kg either with or without angiotensin II treatment at a dose of 0.7 mg/kg/day for 7 days. Protein expression of ferritin and heme oxygenase-1, an oxidative stress-sensitive gene, was determined by Western blot analysis and immunohistochemistry. Results: Administration of iron dextran did not significantly increase proteinuria or decrease creatinine clearance in the rats with or without angiotensin II treatment. Prussian blue staining showed that iron deposition was observed mainly in the glomerular and medullar regions in the iron dextran-treated rats, but in the tubular epithelial cells in angiotensin II-infused rats. Administration of iron dextran upregulated ferritin, but not heme oxygenase-1. Conclusion: Iron dextran did not enhance or cause the renal dysfunction in the angiotensin II-treated or untreated rats, respectively. The distribution of deposited iron and presumably the type of iron compound administered may be important determinants of the development of renal injury.
Interaction between the Tryptophan Hydroxylase Gene and the Serotonin Transporter Gene in Schizophrenia but Not in Bipolar or Unipolar Affective Disorders
Authors: Chotai Jayanti , Serretti Alessandro , Lorenzi Cristina
Published: December 2004

Increasing focus is being given to identify possible combinations of genes related to specific clinical phenotypes. In our sample of 814 patients comprising 114 with schizophrenia, 416 with bipolar affective disorder and 284 with unipolar affective disorder, we studied interactions between the tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR), and the dopamine receptor (DRD4) genes in relation to five major psychiatric symptomatology scores. There was significant interaction between the TPH and the 5-HTTLPR genes. With an increasing number of short (s) alleles of 5-HTTLPR, the scores for delusions, disorganization and negative symptoms were significantly decreasing among subjects having the TPH genotype AA but increasing among subjects having the TPH genotype AC, yielding the highest scores for the combinations AA × ll and AC × ss. Since high scores on just delusions, disorganization and negative symptoms but low scores on excitement and depression were found among subjects with schizophrenia, we conducted comparisons among the three diagnostic categories and controls as regards the combined TPH × 5-HTTLPR genotype distribution. Schizophrenia subjects had a significantly different distribution of the genotype combination for TPH × 5-HTTLPR as compared to 241 controls or to unipolar or bipolar subjects, and had significantly higher frequencies of AA × ll and of AC × ss. Thus, an interaction between TPH and 5-HTTLPR genes constitutes susceptibility to schizophrenia, thereby yielding apparent relationships between the major psychiatric symptomatology scores and genotype combinations in samples that are obtained by pooling schizophrenia with other diagnostic categories.
Sensation Seeking, Sexual Curiosity and Testosterone in Inmates
Authors: Aluja Anton , García Luis F.
Published: December 2004

The relationships between sensation seeking, curiosity about sex, and total and free testosterone in inmates were investigated. The role of other hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and sex hormone-binding globulin (SHBG) in these relationships was also analyzed. Previous analysis allowed the deletion of extreme hormone values affecting the distribution of the variables. In spite of obtaining a high mean for SHBG, relationships between hormones were appropriate. It was observed that higher values of SHBG produce an increment in total testosterone, but not in free testosterone. Positive relationships between total testosterone and the Disinhibition scale of the Sensation Seeking Scale Form V were replicated, although they were affected by SHBG. Significant relationships between total and free testosterone and curiosity about sex were also found. LH and FSH did not influence these patterns of relations. It was suggested that relationships between SHBG and sensation seeking in inmates could be mediated by items referring to alcohol and drugs. The high levels of SHBG observed in the sample reinforced this suggestion. In spite of the role of SHBG, subjects who were desinhibited and concerned about sex presented higher concentrations of total and free testosterone. The results support Zuckerman’s sensation seeking theory.
Anxiolytic Effect of Hepatocyte Growth Factor Infused into Rat Brain
Authors: Isogawa Koichi , Akiyoshi Jotaro , Kodama Kensuke , Matsushita Hirotaka , Tsutsumi Takashi , Funakoshi Hiroshi , Nakamura Toshikazu
Published: December 2004

Background: Hepatocyte growth factor (HGF) has the capacity to selectively direct thalamocortical projections into an intermediate target, the pallidum, and eventually to their final cortical destination. HGF may have a role in the mediation of anxiety. Very little is known about other central behavioral effects of HGF. Objective: Our aim was to determine what effect HGF has on anxiety in rats. Methods: HGF was infused at a constant rate into cerebral lateral ventricles and its effect on anxiety in rats was monitored. Results: In the elevated plus maze test and the black and white box test, HGF administration caused all indicators of anxiety to increase. No significant effect on general locomotor activity was seen. Conclusion: HGF infusion into the brain produces an anxiolytic effect.
p47phox Associates With the Cytoskeleton Through Cortactin in Human Vascular Smooth Muscle Cells
Authors: Touyz R.M. , Yao G. , Quinn M.T. , Pagano P.J. , Schiffrin E.L.
Published: December 2004

Objective—

We tested the hypothesis that p47phox associates with the actin cytoskeleton, enabling site-directed activation of NAD(P)H oxidase, and assessed whether these actions influence reactive oxygen species (ROS) generation and signaling by angiotensin II (Ang II) in vascular smooth muscle cells (VSMCs) from human resistance and coronary arteries.

Methods and Results—

Electroporation of anti-p47phox antibody into VSMCs abrogated Ang II-mediated O

2
generation, establishing the requirement for p47phox in this response. Immunfluorescence confocal microscopy demonstrated a cytosolic distribution of p47phox in basal conditions. After Ang II stimulation, p47phox rearranged in a linear fashion, colocalizing with F-actin. Co-immunoprecipitation studies confirmed an association between p47phox and actin and demonstrated an interaction with the actin-binding protein cortactin. Cytoskeletal disruption with cytochalasin prevented p47phox:actin interaction and attenuated ROS formation and p38MAP kinase and Akt phosphorylation by Ang II. Intracellular ROS generation in response to LY83583 (O

2
generator) or exogenous H
2
O
2
and Ang II-induced ERK1/2 activation were unaltered by cytochalasin.

Conclusions—

The p47phox:actin interaction, through cortactin, plays an important role in Ang II-mediated site-directed assembly of functionally active NAD(P)H oxidase, ROS generation, and activation of redox-sensitive p38MAP kinase and Akt, but not ERK1/2. These findings demonstrate the importance of an intact actin-cytoskeleton in NAD(P)H oxidase regulation and redox signaling by Ang II in human VSMCs.
Transgenic Expression of Fatty Acid Transport Protein 1 in the Heart Causes Lipotoxic Cardiomyopathy
Authors: Chiu Hsiu-Chiang , Kovacs Attila , Blanton Robert M. , Han Xianlin , Courtois Michael , Weinheimer Carla J. , Yamada Kathryn A. , Brunet Sylvain , Xu Haodong , Nerbonne Jeanne M. , Welch Michael J. , Fettig Nicole M. , Sharp Terry L. , Sambandam Nandakumar , Olson Krista M. , Ory Daniel S. , Schaffer Jean E.
Published: December 2004

Evidence is emerging that systemic metabolic disturbances contribute to cardiac myocyte dysfunction and clinically apparent heart failure, independent of associated coronary artery disease. To test the hypothesis that perturbation of lipid homeostasis in cardiomyocytes contributes to cardiac dysfunction, we engineered transgenic mice with cardiac-specific overexpression of fatty acid transport protein 1 (FATP1) using the α-myosin heavy chain gene promoter. Two independent transgenic lines demonstrate 4-fold increased myocardial free fatty acid (FFA) uptake that is consistent with the known function of FATP1. Increased FFA uptake in this model likely contributes to early cardiomyocyte FFA accumulation (2-fold increased) and subsequent increased cardiac FFA metabolism (2-fold). By 3 months of age, transgenic mice have echocardiographic evidence of impaired left ventricular filling and biatrial enlargement, but preserved systolic function. Doppler tissue imaging and hemodynamic studies confirm that these mice have predominantly diastolic dysfunction. Furthermore, ambulatory ECG monitoring reveals prolonged QT
c
intervals, reflecting reductions in the densities of repolarizing, voltage-gated K
+
currents in ventricular myocytes. Our results show that in the absence of systemic metabolic disturbances, such as diabetes or hyperlipidemia, perturbation of cardiomyocyte lipid homeostasis leads to cardiac dysfunction with pathophysiological findings similar to those in diabetic cardiomyopathy. Moreover, the MHC-FATP model supports a role for FATPs in FFA import into the heart in vivo.
Collagen Triple Helix Repeat Containing 1, a Novel Secreted Protein in Injured and Diseased Arteries, Inhibits Collagen Expression and Promotes Cell Migration
Authors: Pyagay Peter , Heroult Mélanie , Wang Qiaozeng , Lehnert Wolfgang , Belden John , Liaw Lucy , Friesel Robert E. , Lindner Volkhard
Published: December 2004

Collagen triple helix repeat containing 1 (
Cthrc1
) was identified in a screen for differentially expressed sequences in balloon-injured versus normal arteries. Cthrc1 expression was not detectable in normal arteries. However, on injury it was transiently expressed by fibroblasts of the remodeling adventitia and by smooth muscle cells of the neointima. It was also found in the matrix of calcifying human atherosclerotic plaques. CTHRC1 is a secreted 28-kDa protein that is glycosylated and highly conserved from lower chordates to mammals. A short collagen motif with 12 Gly-X-Y repeats appears to be responsible for trimerization of the protein and this renders the molecule susceptible to cleavage by collagenase. Cthrc1 mRNA expression levels are increased in response to transforming growth factor-β and bone morphogenetic protein-4. Cell migration assays performed with CTHRC1-overexpressing fibroblasts and smooth muscle cells demonstrate that increased CTHRC1 levels are associated with enhanced migratory ability. Furthermore, CTHRC1 overexpression caused a dramatic reduction in collagen type I mRNA and protein levels. Our data indicate that the novel molecule CTHRC1 is transiently expressed in the arterial wall in response to injury where it may contribute to vascular remodeling by limiting collagen matrix deposition and promoting cell migration.
A Peroxisome Proliferator-Activated Receptor-γ Agonist Reduces Infarct Size in Transient but Not in Permanent Ischemia
Authors: Shimazu Tomokazu , Inoue Ikuo , Araki Nobuo , Asano Yoshio , Sawada Masahiko , Furuya Daisuke , Nagoya Harumitsu , Greenberg Joel H.
Published: December 2004

Background and Purpose—

Activators of peroxisome proliferator-activated receptor-γ (PPARγ), a member of the PPAR family, increase levels of CuZn-superoxide dismutase (SOD) in cultured endothelium, suggesting a mechanism by which it may exert its protective effect within the brain. These properties raise the question of whether a PPARγ agonist may be neuroprotective in models of ischemia without reperfusion, in which oxidative injury is less prevalent.

Methods—

In 2 groups of rats, 90 minutes of middle cerebral artery (MCA) occlusion was followed by 1 day of reperfusion, with 1 group receiving pioglitazone (a PPARγ agonist) starting 72 hours before MCA occlusion (MCAO) and continuing through the day of occlusion, whereas the other group received vehicle only. In 2 comparable groups, the MCA was occluded permanently. One day after occlusion, the animals were tested neurologically and infarct volumes were calculated. In a separate group, rats were treated with pioglitazone or vehicle for 4 days. Tissue was obtained from the cortex and the striatum 2 hours into reperfusion after 90 minutes of MCAO, and the tissue was examined for CuZn-SOD by Western blot.

Results—

Results show a significant reduction in infarct size in the treated rats, with transient MCAO but not permanent MCAO. There was also an improvement in neurological score in the treated animals after transient MCAO. The level of CuZn-SOD was increased in the cortex in treated animals.

Conclusions—

These data, which show that a PPARγ agonist reduces infarct size in transient but not permanent MCAO, suggest that the role of PPARγ is specific to events occurring during reperfusion. Our data point to CuZn-SOD as the mediator of this neuroprotection.
Risk Factors for Stroke in Subjects With Normal Blood Pressure
Authors: Li Cairu , Engström Gunnar , Hedblad Bo , Berglund Göran , Janzon Lars
Published: December 2004

Background and Purpose—

Although stroke is strongly associated with hypertension, some individuals with normal blood pressure (BP) experience a stroke. This prospective study explored risk factors for stroke in subjects with normal BP.

Methods—

A total of 11 228 men and 17 174 women, 45 to 73 years old, were examined in a population-based cohort study. Normal BP was defined as BP <140/90 mm Hg and no treatment for hypertension. The incidence of stroke was followed over a mean period of 6 years.

Results—

In the cohort, 10 938 (38%) had normal BP. Of them, 56 patients experienced a first-ever stroke (12% of all stroke). Compared with subjects without stroke during follow-up, these stroke subjects were older, had lower education, were often smokers and alcohol nondrinkers, and had a history of coronary heart disease (CHD), gastric ulcer, or renal calculus. Subjects with stroke had a higher body mass index (BMI) and a high-normal BP (130 to 139/85 to 89 mm Hg) more often. In a backward stepwise Cox-regression analysis, age (per 1 year; relative risk [RR], 1.12), current smoking (RR, 3.21), BMI (per SD; RR, 1.39), high-normal diastolic BP (RR, 2.35), history of CHD (RR, 4.92), and gastric ulcer (RR, 2.21) remained significantly associated with incidence of stroke.

Conclusion—

In subjects with normal BP, there are a number of potentially modifiable risk factors associated with an increased incidence of stroke.
Redefining Borderline Syndromes as Posttraumatic and Rediscovering Emotional Containment as a First Stage in Treatment
Authors: Goodwin Jean M.
Published: December 2004

This brief review traces the evolution of clinical understanding about borderline syndromes during the last three decades of the 20th century. The focus shifted from descriptive phenomenology in the 1970s to documenting linkages with childhood trauma in the 1980s. In the 1990s, effective and teachable techniques for emotional containment in these conditions were developed and evaluated for efficacy.
Thoughts on Interpersonal Violence and Lessons Learned
Authors: Pierce Robert
Published: December 2004

Although interpersonal violence is evident in all strata of society, every geographical area in the country, and across each gender, it takes courage to acknowledge our passivity about the phenomena, particularly when people of color are involved. Thus, the mass incarcerations of African American men and women and data citing the overrepresentation of African American children not being adequately served in the child welfare system are highlighted to address the three questions posed to authors: What have we learned about violence and trauma over two decades? What should be learned over the next 10 years about violence and trauma? What methodologies exist that show promise of affecting a better understanding of violence and trauma?
The Most Important Things Learned About Violence and Trauma in the Past 20 Years
Authors: Carlson Bonnie E.
Published: December 2004

In the past 2 decades, important insights have been gained regarding violence and trauma. Complications occur in how violence and trauma, their causes, and their effects on victims should be defined. Violence and abuse to women—physical, sexual, and emotional—are not rare events and are most often perpetrated by partners or acquaintances rather than strangers and occur in nonmarital as well as marital relationships, including same-sex relationships. A promising methodological innovation in the study of violence and trauma is the use of longitudinal designs. Innovations in treatments for victims such as evidence-based interventions have been slow to emerge; they include eye movement desensitization and reprocessing (EMDR) and the Seeking Safety group intervention for drug-abusingwomen with traumahistories. Future research should address increased understanding of variation in individual responses to violence and trauma, matching of treatment to different types of male offenders, better understanding of how culture affects violence perpetration and victimization, and evaluation of domestic violence interventions.
KIT exon 8 mutations associated with core-binding factor (CBF)–acute myeloid leukemia (AML) cause hyperactivation of the receptor in response to stem cell factor
Authors: Kohl Tobias M. , Schnittger Susanne , Ellwart Joachim W. , Hiddemann Wolfgang , Spiekermann Karsten
Published: December 2004

KIT exon 8 mutations are located in the extracellular portion of the receptor and are strongly associated with core-binding factor (CBF)-acute myeloid leukemia (AML). To characterize the functional role of these mutants, we analyzed the proproliferative and antiapoptotic potential of 3 KIT exon 8 mutations in interleukin 3 (IL-3)-dependent Ba/F3 cells. All KIT exon 8 mutants induced receptor hyperactivation in response to stem cell factor (SCF) stimulation in terms of proliferation and resistance toward apoptotic cell death. A representative KIT exon 8 mutant showed spontaneous receptor dimerization, phosphorylation of mitogen-activated protein kinase (MAPK), and conferred IL-3-independent growth to Ba/F3 cells. MAPK and phosphatidylinositol 3-kinase (PI3-kinase) activation was essential for the phenotype of this mutant. Additionally, imatinib inhibited proliferation of KIT exon 8 mutant-expressing Ba/F3 cells. Our data show that KIT exon 8 mutations represent gain-of-function mutations and might represent a new molecular target for treatment of CBF leukemias. (Blood. 2005;105:3319-3321)
IL-4 supports the generation of a dendritic cell subset from murine bone marrow with altered endocytosis capacity
Authors: Menges Mauritius , Baumeister Thomas , Rössner Susanne , Stoitzner Patrizia , Romani Nikolaus , Gessner André , Lutz Manfred B
Published: December 2004

Dendritic cells (DC) of myeloid origin can be generated from mouse bone marrow (BM) using granulocyte macrophage-colony stimulating factor (GM-CSF). Immature major histocompatibility complex (MHC) IIlow DC are known to bear a high endocytosis capacity, in contrast to DC precursors and mature DC. Now we found that a subset of MHC IIlow DC in BM-DC cultures is unable to exert mannose receptor-mediated endocytosis of fluorescein isothiocyanate (FITC)-dextran (DX) and resembles immature Langerhans cells (LC). The FITC-DX endocytosis activity of LC-like cells occurs at an earlier stage of development, where the surface MHC II expression is absent or very weak. This LC-like subset expresses higher levels of E-cadherin but lower amounts of the markers Gr-1, scavenger receptor 2F8, and CD11b, when compared with the highly endocytic DC subset. The latter myeloid DC resemble monocyte-derived DC (MoDC). The sorted LC-like population develops completely and exclusively into mature MHC IIhigh DC, and the MoDC-like cells remain immature MHC IIlow DC or develop into adherent MHC IIneg macrophages or mature into MHC IIhigh DC. The development of LC-like cells is promoted by interleukin-4. Thus, we show here that the simultaneous development of LC-like and MoDC-like DC subsets occurs in standard bulk cultures with GM-CSF, suggesting the existence of two different precursors for LC and MoDC in BM.
Biological activities of reverse signal transduction through CD137 ligand
Authors: Schwarz Herbert
Published: December 2004

CD137 is a member of the tumor necrosis factor receptor family and a potent regulator of T cell activities. Agonists of CD137 have been used widely and successfully to treat cancer in animal models, and recently, it has become evident that CD137 agonists can also be used to treat autoimmune disease. An aspect of the CD137 receptor/ligand system, which has been comparatively little-explored, is its ability of reverse signaling. Just as is CD137, the CD137 ligand is also expressed as a cell membrane protein, and it too can transduce signals into the cells on which it is expressed. This bidirectional signaling capacity allows the CD137 receptor/ligand system to mediate extensive cross-talk between immune cells and between immune and nonimmune cells. This review summarizes the known activities of the CD137 ligand on the different leukocyte subsets and on cancer cells and discusses their influence on the course of immune responses.
Strategies and Methods for Research on Sex Differences in Brain and Behavior
Authors: Becker Jill B. , Arnold Arthur P. , Berkley Karen J. , Blaustein Jeffrey D. , Eckel Lisa A. , Hampson Elizabeth , Herman James P. , Marts Sherry , Sadee Wolfgang , Steiner Meir , Taylor Jane , Young Elizabeth
Published: December 2004

Female and male brains differ. Differences begin early during development due to a combination of genetic and hormonal events and continue throughout the lifespan of an individual. Although researchers from a myriad of disciplines are beginning to appreciate the importance of considering sex differences in the design and interpretation of their studies, this is an area that is full of potential pitfalls. A female’s reproductive status and ovarian cycle have to be taken into account when studying sex differences in health and disease susceptibility, in the pharmacological effects of drugs, and in the study of brain and behavior. To investigate sex differences in brain and behavior there is a logical series of questions that should be answered in a comprehensive investigation of any trait. First, it is important to determine that there is a sex difference in the trait in intact males and females, taking into consideration the reproductive cycle of the female. Then, one must consider whether the sex difference is attributable to the actions of gonadal steroids at the time of testing and/or is sexually differentiated permanently by the action of gonadal steroids during development. To answer these questions requires knowledge of how to assess and/or manipulate the hormonal condition of the subjects in the experiment appropriately. This article describes methods and procedures to assist scientists new to the field in designing and conducting experiments to investigate sex differences in research involving both laboratory animals and humans.
Cross-Talk between the Interleukin-6 and Prostaglandin E2 Signaling Systems Results in Enhancement of Osteoclastogenesis through Effects on the Osteoprotegerin/Receptor Activator of Nuclear Factor-κB (RANK) Ligand/RANK System
Authors: Liu Xin-Hua , Kirschenbaum Alexander , Yao Shen , Levine Alice C.
Published: December 2004

The osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL)/receptor activator of nuclear factor-κB (RANK) system is the dominant and final mediator of osteoclastogenesis. Abnormalities of this system have been implicated in the pathogenesis of many skeletal diseases. Cyclooxygenase (COX)-2 and prostaglandin (PG)E2, a major eicosanoid product of the COX-2-catalyzed pathway, play key roles in normal bone tissue remodeling. PGE2 exerts its actions by binding and activating the E series of prostaglandin (EP) receptor. Activation of EP2 and EP4 receptors is associated with PGE2-induced osteoclast differentiation. IL-6, a major proinflammatory cytokine, has also been reported to induce osteoclast differentiation. Although interactions between the COX-2/PGE2 and IL-6 systems have been described in bone cells, the mechanisms underlying these cooperative signaling pathways and the possible involvement of the OPG/RANKL/RANK system have not been fully elucidated. We demonstrate that COX-2, PGE2, and IL-6 stimulate osteoblast growth and osteoclast differentiation. Effects on osteoclast differentiation, particularly with IL-6, were most marked when osteoclast precursor cells were grown in coculture with osteoblasts, indicating a possible role of the RANK/RANKL/OPG system. COX-2 and PGE2 stimulated osteoclastogenesis through inhibition of OPG secretion, stimulation of RANKL production by osteoblasts, and up-regulation of RANK expression in osteoclasts. PGE2 stimulated IL-6 secretion by bone cells, whereas COX-2 inhibitors decreased this same parameter. IL-6, in turn, increased PGE2 secretion, COX-2, and EP receptor subtype expression in bone cells. Finally, IL-6 was the mediator of PGE2-induced suppression of OPG production by osteoblasts. These findings provide evidence for cross-talk between the PGE2 and IL-6 signaling enhance osteoclast differentiation via effects on the OPG/RANKL/RANK system in bone cells.
Validation of RNA Arbitrarily Primed PCR Probes Hybridized to Glass cDNA Microarrays: Application to the Analysis of Limited Samples
Authors: Grau Mònica , Solé Xavier , Obrador Antònia , Tarafa Gemma , Vendrell Elisenda , Valls Joan , Moreno Victor , Peinado Miquel A , Capellá Gabriel
Published: December 2004

Background: The applicability of microarray-based transcriptome massive analysis is often limited by the need for large amounts of high-quality RNA. RNA arbitrarily primed PCR (RAP-PCR) is an unbiased fingerprinting PCR technique that reduces both the amount of initial material needed and the complexity of the transcriptome. The aim of this study was to evaluate the feasibility of using hybridization of RAP-PCR products as transcriptome representations to analyze differential gene expression in a microarray platform.

Methods: RAP-PCR products obtained from samples with limited availability of biological material, such as experimental metastases, were hybridized to conventional cDNA microarrays. We performed replicates of self-self hybridizations of RAP-PCR products and mathematical modeling to assess reproducibility and sources of variation.

Results: Gene/slide interaction (47.3%) and the PCR reaction (33.8%) accounted for the majority of the variability. From these observations, we designed a protocol using two pools of three independent RAP-PCR reactions coming from two independent reverse transcription reactions hybridized in duplicate and evaluated them in the analyses of paired xenograft-metastases samples. Using this approach, we found that HER2 and MMP7 may be down-regulated during distal dissemination of colorectal tumors.

Conclusion: RAP-PCR glass array hybridization can be used for transcriptome analysis of small samples.
Modified Moments and Orthogonal Rational Functions
Authors: Van Deun J. , Bultheel A.
Published: December 2004

In a series of articles [9, 10, 11] about the numerical computation of orthogonal polynomials on a subset of the real line, Gautschi shows that computing orthogonal polynomials starting from the moments μk = ∫ xkdμ(x) of the measure is generally an ill‐conditioned problem. However, in [10] an alternative approach is presented, based on so‐called modified moments, which works better in certain situations. In this paper we generalize these results to the computation of orthogonal rational functions and provide a new modified moment algorithm, based on the connection between modified moments and interpolatory quadrature. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Synthesis of polystyrene‐supported glucosamine resin and its adsorption properties for metal ions
Authors: Sun Changmei , Qu Rongjun , Wang Chunhua , Ji Chunnuan , Cheng Guoxiang
Published: December 2004

A novel chelating resin polystyrene‐supported glucosamine was prepared by the reaction of chloromethylated polystyrene with glucosamine hydrochlorate, using anhydrous potassium carbonate as catalyst and dimethylformamide as solvent. Infrared spectra and elementary analysis were used to confirm its structure. The adsorption of the resin for Cu2+, Ni2+, Hg2+, Co2+, Cd2+, and Pb2+ was investigated, as well as various factors affecting the adsorption such as time, temperature, ion concentration, and pH. The results showed that the resin had good adsorption capacities for Cu2+, Ni2+, and Hg2+. The adsorption was controlled by liquid film diffusion and adsorption isothermal data could be well interpreted by the Freundlich equation. Values of adsorption activation energy and adsorption Gibbs free energy were calculated. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 95: 890–896, 2005