bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification, measurement and interpretation of tree rings in woody species from mediterranean climates
Authors: CHERUBINI PAOLO , GARTNER BARBARA L. , TOGNETTI ROBERTO , BRÄKER OTTO U. , SCHOCH WERNER , INNES JOHN L. 
Published: March 2003

ABSTRACTWe review the literature dealing with mediterranean climate, vegetation, phenology and ecophysiology relevant to the understanding of tree‐ring formation in mediterranean regions. Tree rings have been used extensively in temperate regions to reconstruct responses of forests to past environmental changes. In mediterranean regions, studies of tree rings are scarce, despite their potential for understanding and predicting the effects of global change on important ecological processes such as desertification. In mediterranean regions, due to the great spatio‐temporal variability of mediterranean environmental conditions, tree rings are sometimes not formed. Often, clear seasonality is lacking, and vegetation activity is not always associated with regular dormancy periods. We present examples of tree‐ring morphology of five species (Arbutus unedo, Fraxinus ornus, Quercus cerris, Q. ilex, Q. pubescens) sampled in Tuscany, Italy, focusing on the difficulties we encountered during the dating. We present an interpretation of anomalies found in the wood structure and, more generally, of cambial activity in such environments. Furthermore, we propose a classification of tree‐ring formation in mediterranean environments. Mediterranean tree rings can be dated and used for dendrochronological purposes, but great care should be taken in selecting sampling sites, species and sample trees.
A sigmoidal transcriptional response: cooperativity, synergy and dosage effects
Authors: VEITIA REINER A. 
Published: March 2003

ABSTRACTA sigmoidal transcriptional response (STR) is thought to act as amolecular switch to control gene expression. This nonlinear behaviour arises as a result of the cooperative recognition of a promoter/enhancer by transcription factors (TFs) and/or their synergy to attract the basal transcriptional machinery (BTM). Although this cooperation between TFs is additive in terms of energy, it leads to an exponential increase in affinity between the BTM and the pre‐initiation complexes. This exponential increase in the strength of interactions is the principle that governs synergistic systems. Here, I propose a minimalist quasi‐equilibrium model to explore qualitatively the STR taking into account cooperative recognition of the promoter/enhancer and synergy. Although the focus is on the effect of activators, a similar treatment can be applied to inhibitors. One of the main insights obtained from the model is that generation of a sigmoidal threshold is possible even in the absence of cooperative DNA binding provided the TFs synergistically interact with the BTM. On the contrary, when there is cooperative binding, the impact of synergy diminishes. It will also be shown that a sigmoidal response to a morphogenetic gradient can be used to generate a nested gradient of another morphogen. Previously, I had proposed that halving the amounts of TFs involved in sigmoidal transcriptional switches could account for the abnormal dominant phenotypes associated with some of these genes. This phenomenon, called haploinsufficiency (HI), has been recognised as the basis of many human diseases. Although a formal proof linking HI and a sigmoidal response is lacking, it is tempting to explore the model from the perspective of dosage effects.
Workplace trauma and the law
Authors: Tehrani Noreen 
Published: March 2003

AbstractThe law places increasing responsibilities on organizations to protect its workforce from psychological injury. This paper looks at the development of British law relating to traumatic stress and explores a growing concern of clinicians that the law and the legal processes themselves may increase the psychological injury of victims of traumatic stress. The statutory requirement for organizations to provide effective support for employees following a traumatic incident is enshrined in law. However organizations are confused by the conflicting statements on the effectiveness of debriefing and trauma counselling.
German version of clinician‐administered PTSD scale
Authors: Schnyder Ulrich , Moergeli Hanspeter 
Published: March 2003

AbstractThis study assessed the reliability of a German translation of the Clinician‐Administered PTSD Scale (CAPS) by using data from 45 survivors of accidents who were hospitalized at the department of traumatology of a university hospital. Assessments were carried out 5 days (Time 1) and 6 months (Time 2) after the accident. Internal consistency proved to be comparable to that of the original English version: Cronbach's alpha was .88 at'T1 and .92 at T2 for the CAPS total score. The CAPS correlated significantly with the validated German version of the Impact of Event Scale (lES) (T1: r = .56, T2: r = .78). The data suggest that the German version of the CAPS is a reliable instrument for the assessment of posttraumatic stress disorder symptomatology in accident victims. Further studies are necessary' to validate further the questionnaire.
Making sense of repetition phenomena by integrating psychotraumatology and psychodynamic psychotherapy
Authors: Ørner Roderick J. , Stolz Peter 
Published: March 2003

AbstractPsychotherapy and psychotraumatology share a preoccupation with repetition phenomena, manifested as transference, compulsions to repeat, or intrusive reexperiencing. Terminological diversity obscures compelling similarities between these repetition phenomena and discourages speculation about processes involved in their genesis. This paper remedies these oversights by integrating recent empirical evidence pertaining to memory with European intellectual traditions embraced by its pioneering dynamic psychotherapists. Using dreams as a prototype repetition, the phenomenological diversity of repetition phenomena is shown to be reconcilable with current evidence about memory encoding, storage, and retrieval. Differences in persistence, intensity, pervasiveness, and treatment resilience of repetition phenomena are explained using concepts derived from psychological and biological sciences. Implications for psychotherapeutic theory, practice, and evaluation are considered.
Posttraumatic sequelae in a community hit by an avalanche
Authors: Finnsdottir Thorunn , Elklit Ask 
Published: March 2003

AbstractThe posttraumatic sequelae for 104 adult inhabitants from the town of Flateyri. Iceland, were studied 10 weeks after an avalanche hit the town killing 20 people. Eighty‐seven adults from the neighboring town of Thingeyri constituted a control group. On the basis of the General Health Questionnaire (GHQ‐30), 25% of the Flateyri group (twice as many than in Thingeyri) reached a level of psychiatric caseness. The most common symptoms were intrusive thoughts and feelings, tension, sadness, and anxiety. The loss of family members was associated with symptomatology. A high number of former life events correlated more strongly with distress symptoms than with the individual appraisal of these events. Distress symptoms were related to gender, age, and education.
Introduction of a ketogenic diet in young infants
Authors: Klepper J. , Leiendecker B. , Bredahl R. , Athanassopoulos S. , Heinen F. , Gertsen E. , Flörcken A. , Metz A. , Voit T. 
Published: March 2003

AbstractThe ketogenic diet is a rational treatment for pyruvate dehydrogenase complex deficiency (McKusick 312170) and GLUT1 deficiency syndrome (McKusick 138140). An increasing number of patients are diagnosed in early infancy, but few data are available on the introduction of a ketogenic diet in this age group. GLUT1 deficiency syndrome was suspected in four infants presenting with seizures and unexplained hypoglycorrhachia. A ketogenic diet was introduced at 6–28 weeks of age. Ketosis was initiated by fasting, monitored by bedside blood glucose and 3‐hydroxybutyrate determinations, and was maintained successfully using supplemented carbohydrate‐free infant formula and emulgated triglycerides. All patients developed ketosis within 24 h. 3‐Hydroxybutyrate concentrations available at the bedside correlated inversely with the base excess. At glucose levels ≤40 mg/dl patients remained asymptomatic in the presence of ketones. The ketogenic formula was tolerated well, parental compliance was good, and all patients remained seizure‐free on the diet. GLUT1 deficiency was confirmed in two patients; the diet was discontinued in the other two patients. In one infant, failure to thrive on medium‐chain triglycerides was effectively reversed using long‐chain triglycerides. Urine dipstick analyses failed to detect ketosis in another infant. Adverse effects of the diet were limited to renal stones in one patient. The ketogenic diet can be introduced and maintained successfully in young infants using long‐chain fat emulsion. Monitoring 3‐hydroxybutyrate at the bedside was useful for metabolic control and superior to urine dipstick analysis. Seizure control was effective and adverse effects were limited, but evaluation of the long‐term effects of the ketogenic diet in this age group must await ongoing studies.
Ramipril treatment in a patient with glycogen storage disease I non‐A
Authors: Giannì M. L. , Bonvissuto M. , Gallieni M. , Testolin C. , Racchi E. , Riva E. 
Published: March 2003

AbstractWe studied the effect of ramipril on proteinuria and mild hypertension in a 21‐year‐old patient affected by glycogen storage disease type I non‐A. After few months of therapy we obtained a decrease in total urine protein excretion that later re‐increased in spite of the high dose of ACE inhibitor. Even if ACE inhibitors are the only effective therapy for GSD I nephropathy, further studies are requested.
CblE type of homocystinuria due to methionine synthase reductase deficiency: Clinical and molecular studies and prenatal diagnosis in two families
Authors: Zavaď'áková P. , Fowler B. , Zeman J. , Suormala T. , Pšistoupilová K. , Kožich V. 
Published: March 2003

AbstractThe cblE type of homocystinuria is a rare autosomal recessive disorder, which manifests with megaloblastic anaemia and developmental delay in early childhood. This disease is caused by a defect in reductive activation of methionine synthase (MTR). Our study was directed at clinical, biochemical, enzymatic and molecular characterization of two Czech patients with the cblE type of homocystinuria. Case 1 involves a 20‐year‐old mentally retarded patient who presented with megaloblastic anaemia at 10 weeks of age. She was treated with folates and vitamin B12, and subsequent attempts to cease administration of folates led to recurrence of megaloblastic anaemia. Biochemical features included severe hyperhomocysteinaemia and hypomethioninaemia and in fibroblasts defective formation of methionine from formate, and no complementation with cblE cells. Subsequent molecular analysis of the methionine synthase reductase (MTRR) gene revealed compound heterozygosity for a transition c.1459G>A (G487R) and a 2 bp insertion (c.1623–1624insTA). Case 2 involves an 8‐year‐old girl with nystagmus and developmental delay in whom megaloblastic anaemia was detected at 11 weeks of age. Severe hyperhomocysteinaemia with normal methionine levels was found and enzymatic and complementation studies confirmed the cblE defect. This patient is homozygous for a 140 bp insertion (c.903–904ins140). The insertion is caused by a T>C transition within intron 6 of the MTRR gene, which presumably leads to activation of an exon splicing enhancer. In the families of both patients, enzymatic and mutation analyses were successfully used for prenatal diagnosis. Our study expands the knowledge of the phenotypic and genotypic variability of the cblE type of homocystinuria and supports the concept that this disorder is caused by mutations in the MTRR gene.
Mechanisms of endothelial dysfunction after ionized radiation: selective impairment of the nitric oxide component of endothelium‐dependent vasodilation
Authors: Soloviev Anatoly I , Tishkin Sergey M , Parshikov Alexander V , Ivanova Irina V , Goncharov Eugene V , Gurney Alison M 
Published: March 2003

Gamma radiation impairs vascular function, leading to the depression of endothelium‐dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about radiation effects on other endothelial mediators.
This study investigated the mechanisms of endothelial dysfunction in rabbits subjected to whole‐body irradiation from a cobalt60 source.
The endothelium‐dependent relaxation of rabbit aorta evoked by acetylcholine (ACh) or A23187 was impaired in a dose‐dependent manner by irradiation at 2 Gy or above. Inhibition was evident 9 days post‐irradiation and persisted over the 30 day experimental period.
Endothelium‐independent responses to glyceryl trinitrate (GTN), sodium nitroprusside (SNP) and 3‐morpholino‐sydnonimine (SIN‐1) were suppressed over a similar dose range at 7–9 days post‐irradiation, but recovered fully by 30 days post‐irradiation.
In healthy vessels, ACh‐induced relaxation was inhibited by L‐Nω‐nitroarginine (L‐NA; 3×10−4 M) and charybdotoxin (10−8 M) plus apamin (10−6 M) but resistant to indomethacin, indicating the involvement of NO and endothelium‐derived hyperpolarizing factor (EDHF). Supporting this, ACh caused smooth muscle hyperpolarization that was reduced by L‐NA and charybdotoxin plus apamin.
In irradiated vessels, responses to ACh were insensitive to L‐NA but abolished by charybdotoxin plus apamin, indicating selective loss of NO‐mediated relaxation.
In animals treated shortly after irradiation with the antioxidant, α‐tocopherol acetate, the NO‐dependent relaxation was restored without effect on the EDHF‐dependent component.
The results imply that radiation selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium‐dependent relaxation at a reduced level.

British Journal of Pharmacology (2003) 138, 837–844. doi:10.1038/sj.bjp.0705079
Inhibition by pentoxifylline of TNF‐α‐stimulated fractalkine production in vascular smooth muscle cells: evidence for mediation by NF‐κB down‐regulation
Authors: Chen Yung‐Ming , Tu Chao‐Jung , Hung Kung‐Yu , Wu Kwan‐Dun , Tsai Tun‐Jun , Hsieh Bor‐Shen 
Published: March 2003

Fractalkine is a CX3C chemokine for mononuclear leukocytes that is expressed mainly by vascular cells, and regulated by pro‐inflammatory cytokines. This study investigated signal transduction mechanisms by which tumor necrosis factor (TNF)‐α stimulated fractalkine expression in cultured rat vascular smooth muscle cells (VSMCs), and the modulatory effect of a haemorrheologic agent, pentoxifylline, on its production.
TNF‐α (1–50 ng ml−1) stimulated fractalkine mRNA and protein expression in concentration‐ and time‐dependent manners. Pretreatment with calphostin C (0.4 μM, a selective inhibitor of protein kinase C (PKC), and PD98059 (40 μM), a specific inhibitor of p42/44 mitogen‐activated protein kinase (MAPK) kinase, attenuated TNF‐α‐stimulated fractalkine mRNA and protein expression. In contrast, H‐89 (2 μM), a selective inhibitor of cAMP‐dependent protein kinase, wortmannin (0.5 μM), a selective inhibitor of phosphatidylinositol 3‐kinase, and SB203580 (40 μM), a specific inhibitor of p38 MAPK, had no discernible effect.
The ubiquitin/proteosome inhibitors, MG132 (10 μM) and pyrrolidine dithiocarbamate (200 μM), suppressed activation of NF‐κB as well as stimulation of fractalkine mRNA and protein expression by TNF‐α.
TNF‐α‐activated phosphorylation of PKC was blocked by calphostin C, whereas TNF‐α‐augmented phospho‐p42/44 MAPK and phospho‐c‐Jun levels were reduced by PD98059. Neither calphostin C nor PD98059 affected TNF‐α‐induced degradation of I‐κBα or p65 nuclear translocation.
Pretreatment with pentoxifylline (0.1–1 mg ml−1) decreased TNF‐α‐stimulated fractalkine mRNA and protein expression, which was preceded by a reduction in TNF‐α‐activated phosphorylation of PKC, p42/44 MAPK and c‐Jun as well as degradation of I‐κBα and p65/NF‐κB nuclear translocation.
These data indicate that activation of PKC, p42/44 MAPK kinase, and NF‐κB are involved in TNF‐α‐stimulated fractalkine production in VSMCs. Down‐regulation of the PKC, p42/44 MAPK, and p65/NF‐κB signals by PTX may be therapeutically relevant and provide an explanation for the anti‐fractalkine effect of this drug.

British Journal of Pharmacology (2003) 138, 950–958. doi:10.1038/sj.bjp.0705088
Identification of the di‐pyridyl ketone isonicotinoyl hydrazone (PKIH) analogues as potent iron chelators and anti‐tumour agents
Authors: Becker Erika M , Lovejoy David B , Greer Judith M , Watts Ralph , Richardson Des R 
Published: March 2003

In an attempt to develop chelators as potent anti‐tumour agents, we synthesized two series of novel ligands based on the very active 2‐pyridylcarboxaldehyde isonicotinoyl hydrazone (PCIH) group. Since lipophilicity and membrane permeability play a critical role in Fe chelation efficacy, the aldehyde moiety of the PCIH series, namely 2‐pyridylcarboxaldehyde, was replaced with the more lipophilic 2‐quinolinecarboxaldehyde or di‐2‐pyridylketone moieties. These compounds were then systematically condensed with the same group of acid hydrazides to yield ligands based on 2‐quinolinecarboxaldehyde isonicotinoyl hydrazone (QCIH) and di‐2‐pyridylketone isonicotinoyl hydrazone (PKIH). To examine chelator efficacy, we assessed their effects on proliferation, Fe uptake, Fe efflux, the expression of cell cycle control molecules, iron‐regulatory protein‐RNA‐binding activity, and 3H‐thymidine, 3H‐uridine and 3H‐leucine incorporation.
Despite the high lipophilicity of the QCIH ligands and the fact that they have the same Fe‐binding site as the PCIH series, surprisingly none of these compounds were effective. In contrast, the PKIH analogues showed marked anti‐proliferative activity and Fe chelation efficacy. Indeed, the ability of these ligands to inhibit proliferation and DNA synthesis was similar or exceeded that found for the highly cytotoxic chelator, 311. In contrast to the PCIH and QCIH analogues, most of the PKIH group markedly increased the mRNA levels of molecules vital for cell cycle arrest.
In conclusion, our studies identify structural features useful in the design of chelators with high anti‐proliferative activity. We have identified a novel class of ligands that are potent Fe chelators and inhibitors of DNA synthesis, and which deserve further investigation.

British Journal of Pharmacology (2003) 138, 819–830. doi:10.1038/sj.bjp.0705089
Identification of MEK1 as a novel target for the treatment of neuropathic pain
Authors: Ciruela A , Dixon A K , Bramwell S , Gonzalez M I , Pinnock R D , Lee K 
Published: March 2003

In the present study we have attempted to identify changes in gene expression which are associated with neuropathic pain using subtractive suppression hybridization analysis of the lumbar spinal cord of animals suffering streptozocin induced diabetic neuropathy.
Using this approach, we found a significant up‐regulation of several key components of the extracellular signal‐regulated kinase (ERK) cascade. These findings were confirmed by Western blot analysis, which demonstrated that the levels of active ERK1 and 2 correlated with the onset of streptozocin‐induced hyperalgesia.
Intrathecal administration of the selective MAPK/ERK‐kinase (MEK) inhibitor PD 198306 dose‐dependently (1–30 μg) blocked static allodynia in both the streptozocin and the chronic constriction injury (CCI) models of neuropathic pain.
The antihyperalgesic effects of PD 198306, in both the streptozocin and CCI models of neuropathic pain, correlated with a reduction in the elevated levels of active ERK1 and 2 in lumbar spinal cord.
Intraplantar administration of PD 198306 had no effect in either model of hyperalgesia, indicating that changes in the activation of ERKs and the effect of MEK inhibition are localized to the central nervous system.
In summary, we have demonstrated for the first time that the development of neuropathic pain is associated with an increase in the activity of the MAPK/ERK‐kinase cascade within the spinal cord and that enzymes in this pathway represent potential targets for the treatment of this condition.

British Journal of Pharmacology (2003) 138, 751–756. doi:10.1038/sj.bjp.0705103
Preservation of vascular contraction during ageing: dual effect on calcium handling and sensitization
Authors: Matz Rachel L , Sotomayor Maria Alvarez de , Schott Christa , Andriantsitohaina Ramaroson 
Published: March 2003

The present study was aimed to characterize the effects of ageing on vascular contraction by noradrenaline in rat isolated arteries. The existence of vascular bed heterogeneity was investigated in endothelium‐denuded conductance (aorta) and resistance (small mesenteric artery, SMA) arteries, with respect to Ca2+handling, Ca2+sensitization or Ca2+‐independent mechanisms.In both arteries, contractions to noradrenaline were not different between adult and aged rats.In Ca2+‐ free medium, noradrenaline elicited a transient increase in tension that was reduced by the Ca2+mobilizing agents, ryanodine and thapsigargin, in arteries from adult rats. A loss of the thapsigargin‐ but not the ryanodine‐sensitive component of noradrenaline‐induced contraction was observed in the two arteries from aged rats.After depletion of Ca2+stores with noradrenaline, addition of exogenous CaCl2produced a sustained contraction that was decreased to the same extent by the protein kinase C inhibitor, GF 109203X and the tyrosine kinase inhibitor, tyrphostin A‐23, in arteries from adult and aged rats. The Rho‐associated protein kinase inhibitor, Y‐27632, caused identical relaxation of noradrenaline pre‐contracted arteries from both age groups.Basal intracellular calcium ([Ca2+]i) was higher in SMA from aged than from adult rats. In addition, the noradrenaline [Ca2+]i‐force relationship was significantly shifted to the right in the SMA from aged rats.Altogether, these data indicate that responsiveness to noradrenaline is preserved both in conductance and resistance arteries with ageing. The latter results from the association of increased basal [Ca2+]i, changes in Ca2+handling at the level of thapsigargin‐sensitive sarcoplasmic reticulum Ca2+‐ATPases and decreased myofilament sensitivity to Ca2+.British Journal of Pharmacology(2003)138, 745–750. doi:10.1038/sj.bjp.0705104