bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear of Intimacy in Women: Relationship between Attachment Styles and Depressive Symptoms
Authors: Reis Samantha , Grenyer Brin F.S.
Published: December 2004

Background: Preoccupied and fearful attachment have both been associated with depressive symptoms, but it is unclear which attachment style is primarily associated with major depression. While preoccupied attachment denotes a focus on relationships as a source of self-validation, fearful attachment involves an avoidance of relationships for fear of rejection. Present research aims to investigate the relative influence of fearful and preoccupied attachments on self-reported depressive symptoms within both a student and a clinical sample and to examine these associations separately for male and female participants. Sampling and Methods: All participants completed the Relationship Questionnaire and the Beck Depression Inventory. Study 1 assessed attachment ratings and self-reported severity of depression for 71 patients diagnosed with major depression. Study 2 similarly assessed 245 university students, and study 3 compared attachment ratings of the two samples. Results: Both Pearson correlations and partial correlations were examined for both samples. Fearful attachment was associated with self-reported depression severity for females with depression, but attachment styles were unrelated to depression severity for males with depression (study 1). For female university students, both fearful and preoccupied attachment styles were significantly related to depression severity, but again there were no associations for male university students when partial correlations were utilised (study 2). Study 3 revealed significantly higher levels of fearful attachment for women with depression compared with female university students and no significant differences for males overall. Conclusions: For females, the avoidance of intimacy for fear of rejection was associated with a broad spectrum of depressive symptoms. Results highlight gender differences in depressive experiences, and have implications for research into the effects of fearful attachment on social support and the therapeutic alliance. Limitations to this study include the reliance on self-report measures of attachment and depression severity, the small number of male participants in the clinical sample, and the use of a cross-sectional rather than longitudinal design.
Innate Immunity Contributes to Cochlear Adaptive Immune Responses
Authors: Hashimoto Shigehisa , Billings Peter , Harris Jeffrey P. , Firestein Gary S. , Keithley Elizabeth M.
Published: December 2004

Inner ear immune responses mediated by antigen-specific processes are thought to contribute to hearing loss in humans. Systemic activation of innate immunity contributes to immune responses in the central nervous system. We hypothesized that activation of innate immunity can prime the inner ear for adaptive immune responses and exacerbate disease. Mice were systemically immunized with antigen. Three weeks after initial antigen exposure, the antigen was injected intrathecally coincident with systemic injection of lipopolysaccharide (LPS), an activator of innate immunity. Responses were measured by quantifying the leukocyte infiltrate and cochlear IL-1β expression. LPS stimulation markedly amplified the adaptive immune response to exogenous antigen in the inner ear. These data indicate that the cochlea is activated by systemic events that stimulate innate immunity and when antigen is present in the inner ear, a robust cochlear adaptive response is generated. If true in humans, this implies that priming may be an important component in the development of immune-mediated hearing loss.
Che a 1: Recombinant Expression, Purification and Correspondence to the Natural Form
Authors: Barderas Rodrigo , Villalba Mayte , Rodríguez Rosalía
Published: December 2004

Background: Pollinosis to chenopods is one of the main causes of allergy in desertic regions and it is increasing in the South of Europe and Western USA. Che a 1 is a major allergen for chenopod-allergic subjects and belongs to the Ole-e-1-like family of proteins. Methods:Pichia pastoris yeast has been used as expression system to produce the recombinant form of Che a 1 (rChe a 1). The allergen was isolated using a gel permeation column and reverse-phase/high-performance liquid chromatography. Molecular characterization was performed using Edman degradation, mass spectrometry and concanavalin A staining. Sera from patients allergic to chenopod pollen, as well as polyclonal and monoclonal antibodies raised against Ole e 1, were used in immunoblotting, ELISA and inhibition assays for immunological characterization of rChe a 1. Results: The allergen was purified to homogeneity with a final yield of 15 mg/l of cell culture and showed a glycosylated character. N-terminal amino acid sequence of rChe a 1 and molecular mass were according to those of the protein isolated from chenopod pollen. The recombinant allergen maintained the IgG and IgE epitopes of the natural allergen deduced from the immunological assays. Conclusions: Structural and in vitro immunological properties of rChe a 1 produced in P. pastoris were equivalent to those of the natural form of the allergen and, thus, it could be used in testing patients allergic to chenopods.
Desloratadine Inhibits Constitutive and Histamine-Stimulated Nuclear Factor-κB Activity Consistent with Inverse Agonism at the Histamine H1 Receptor
Authors: Wu Ren-Long , Anthes John C. , Kreutner William , Harris Alan G. , West Jr Robert E.
Published: December 2004

Background: The human histamine H1 receptor is constitutively active and exhibits basal activation of nuclear factor-ĸB (NF-ĸB), an important modulator of allergic inflammation. Certain H1 antihistamines have recently been shown to inhibit basal NF-ĸB activity by stabilizing the H1 receptor in an inactive state, a phenomenon called ‘inverse agonism’. Methods: We evaluated the effect of the new H1 antihistamine, desloratadine, on basal and histamine-stimulated NF-ĸB activity and compared it with the activities of other H1 antihistamines. Results: Transiently transfected COS-7 cells co-expressing NF-ĸB-luciferase and the H1 receptor exhibited constitutive NF-ĸB activity. H1 antihistamines reduced basal NF-ĸB activity (rank order of potency: desloratadine > pyrilamine > cetirizine > loratadine > fexofenadine). Histamine stimulated basal NF-ĸB activity 8-fold, which was blocked by H1 antihistamines (rank order of potency: desloratadine > cetirizine > pyrilamine > loratadine > fexofenadine). Neither histamine nor antihistamines had any effect on NF-ĸB activity in the absence of the H1 receptor. Conclusions: Desloratadine, acting through the histamine H1 receptor, inhibited basal NF-ĸB activity and can thus be classified as an inverse agonist. Inhibition of basal and histamine-stimulated NF-ĸB activity may help to explain previously reported inhibitory effects of desloratadine on allergic inflammatory mediators.
A Comprehensive Analysis of Interleukin-4 Receptor Polymorphisms and Their Association with Atopy and IgE Regulation in Childhood
Authors: Woitsch Bernd , Carr David , Stachel Daniel , Schmid Irene , Weiland Stephan K. , Fritzsch Christian , von Mutius Erika , Kabesch Michael
Published: December 2004

Background: The interleukin (IL) 4/IL13 pathway is involved in the regulation of IgE production associated with atopic diseases. Numerous polymorphisms have been identified in the coding region of the IL4 receptor α chain (IL4Ra) and previous association studies have shown conflicting results. Based on their putative functional role, polymorphisms A148G, T1432C and A1652G, located in the coding region of IL4Ra, were selected for association and haplotype studies in a large German population sample (n = 1,120). Methods: Genotyping was performed using allele-specific PCR and restriction-enzyme-based assays. Haplotypes were estimated, and population-derived IgE percentiles (50% IgE >60 IU/ml, 66% IgE >115 IU/ml and 90% IgE >457 IU/ml) were calculated as outcome variables in a haplotype trend regression analysis. Results: In our population, only polymorphism T1432C showed a trend for a protective effect against atopic rhinitis (odds ratio, OR: 0.52, 95% confidence interval, CI: 0.26–1.02, p = 0.05). When haplotypes were calculated, one haplotype was significantly associated with elevated serum IgE levels at the 50th percentile (OR 1.60, 95% CI 1.08–2.37, p = 0.02). Conclusions: These data indicate that IL4Ra polymorphisms, although suggested to be functionally relevant by in vitro studies, have only a minor influence on IgE regulation in our large population sample.
The Allergic March in Pollinosis: Natural History and Therapeutic Implications
Authors: Marogna Maurizio , Falagiani Paolo , Bruno Marco , Massolo Alessandro , Riva Graziella
Published: December 2004

Background: That specific immunotherapy (SIT) can slow the march of allergy has been confirmed in controlled clinical trials. However, an assessment of its effects in everyday life, in a large cohort of patients, might provide further useful information. Methods: This observational study comprised 3,643 patients allergic to pollens; 1,620 with pure allergic rhinitis or rhinitis and intermittent or mild-persistent bronchial asthma, responding poorly to standard pharmacological therapy (SPT), were treated for 3 years with SPT alone (pure rhinitis, n = 890), or combined with continuous SIT (rhinitis and asthma, n = 730). Symptom/drug scores were recorded, respiratory function and skin tests were done, and methacholine challenge was scheduled at the beginning and end of the study. A series of 2,023 patients with pure rhinitis, responsive to SPT, were asked to ‘self-medicate’ as needed, serving as a control group to check the incidence of asthma. Results: The incidence of rhinitis-asthma co-morbidity was highest in the self-medication group (50.8%). Persistent rhinitis was associated with asthma more often than the intermittent form, regardless of the severity of the symptoms that led to progression to asthma in patients with intermittent rhinitis. Treatment with SIT combined with SPT always slowed the allergic march which, however, was not influenced by drugs alone. Conclusions: In routine clinical practice, SIT is effective in preventing the allergic march. Patients with persistent rhinitis, who are at greatest risk of progression to asthma, appear to be the most logical candidates.
Homologous Up-Regulation of Androgen Receptor Expression by Androgen in Vascular Smooth Muscle Cells
Authors: Ma Rui , Wu Saizhu , Lin Qishui
Published: December 2004

Objective: Androgens play an important role in the arterial vascular system, and androgen receptors (AR) have been identified in vascular smooth muscle cells (VSMCs). This study examined the effects of testosterone exposure on AR gene expression in cultured rat aortic smooth muscle cells. Methods: Changes in AR protein and messenger RNA (mRNA) levels after androgen exposure were determined using immunoblotting and Northern blotting analysis respectively. Results: Treatment of synchronized VSMCs with testosterone increased both cytoplasmic and nuclear AR protein expression in a dose- and time-dependent fashion, whereas exposure of VSMCs to androgen for 10 min induced a transient down-regulation of AR protein. Meanwhile, AR mRNA level was also up-regulated, but to a much smaller extent. Pretreatment with transcription inhibitor and translation inhibitor repressed cytoplasmic AR protein levels to 46 and 12% (means) of the androgen treatment control level respectively. Furthermore, androgen up-regulation of intracellular AR protein was partially inhibited by androgen antagonist. Conclusions: Androgen increases AR expression in VSMCs at the level of both transcription and non-transcription.
Hypothalamic Antihypertensive Effect of Irbesartan in Chronic Aortic Coarctated Rats
Authors: Höcht Christian , Opezzo Javier A.W. , Taira Carlos A.
Published: December 2004

The aim of the present work was to study the central and plasma pharmacokinetics of irbesartan (IRB) and its possible hypothalamic antihypertensive effect in sham-operated (SO) and aortic-coarctated (ACo) rats at a chronic hypertensive stage using the microdialysis technique. Anesthetized Wistar rats were used 42 days after ACo or SO. For the study of plasma pharmacokinetics, a vascular shunt probe was inserted into the carotid artery. In a separated experiment, a concentric probe was placed into the anterior hypothalamus for the study of IRB distribution in the central nervous system. Based on the hypothalamic concentrations of IRB reached in ACo rats, the anterior hypothalamus of SO and ACo animals was perfused with a Ringer solution containing approximately 6 µg·ml–1 of the drug. IRB (10 mg·kg–1 i.v.) induced a late decrease of heart rate (HR) in ACo animals (ΔHR: –42 ± 10 bpm, n = 5, p < 0.05 vs. SO rats) but not in SO rats (ΔHR: 11 ± 13 bpm, n = 5). Systemic administration of the drug reduced the mean arterial pressure (MAP) of both experimental groups, but the hypotensive effect was greater in ACo (ΔMAP: –39.9 ± 5.0 mm Hg, n = 5, p < 0.05 vs. SO rats) than in SO rats (ΔMAP: –25.4 ± 2.1 mm Hg, n = 5). A similar pharmacokinetic profile was observed in both experimental groups. Hypothalamic distribution of IRB was greater in ACo (AUC: 730 ± 130 ng·ml–1 h–1, n = 5, p < 0.05 vs. SO rats) than in SO animals (AUC: 283 ± 87 ng·ml–1 h–1, n = 5). The IRB hypothalamic perfusion induced an antihypertensive effect in ACo (ΔMAP: –15.1 ± 1.0 mm Hg, n = 5, p < 0.05 vs. Ringer perfusion) but not in SO rats. In conclusion, the chronic aortic coarctation did not modify the plasma pharmacokinetics of IRB, but it increased the distribution of the drug in the central nervous system. The greater hypotensive effect of IRB observed in ACo animals suggests the involvement of AT1 receptors in the maintenance of the hypertensive stage in chronic ACo rats. The hypotensive effect of IRB in ACo animals could be explained, at least in part, due an action on the anterior hypothalamic angiotensin system.
Hypothalamo-Pituitary-Adrenal Axis-Regulated Stress Response and Negative Feedback Sensitivity Is Altered by Prenatal Morphine Exposure in Adult Female Rats
Authors: Šlamberová Romana , Rimanóczy Ágnes , Riley Michelle A. , Vathy Ilona
Published: December 2004

It has been shown that adult female rats react to stressors more intensely than adult male rats. Our previous work demonstrated that the adrenocorticotropic hormone (ACTH) but not corticosterone (CORT) response to stress is altered by prenatal morphine exposure in adult male rats. Response of the hypothalamo-pituitary-adrenal (HPA) axis to stress is known to be sex specific and dependent on the hormonal fluctuation of the estrous cycle. Therefore, the present study examined the effect of prenatal morphine exposure on the levels of ACTH and CORT before and after restraint stress in adult female rats. Experiment 1 tested ACTH and CORT plasma levels before and after restraint stress in prenatally morphine- and saline-exposed, adult diestrus and proestrus female rats. Prenatal morphine exposure suppressed the restraint stress-induced ACTH levels in both diestrus and proestrus females, but did not have any effects on the basal or stress-induced CORT levels. Experiment 2 examined the sensitivity of negative feedback using the dexamethasone (DEX) (0.001, 0.01, 0.1 and 1.0 mg/kg) suppression test in adult, prenatally morphine- and saline-exposed female rats. In saline-exposed, proestrus but not diestrus females, all doses of DEX were effective in suppressing the restraint stress-induced increase in CORT levels. In both diestrus and proestrus, morphine-exposed females, only the two highest doses of DEX (0.1 and 1.0 mg/kg) were successfully suppressing the stress-induced CORT levels. The stress-induced increase in the ACTH level was suppressed only by the highest dose of DEX (1.0 mg/kg) in both saline- and morphine-exposed, diestrus and proestrus females. Thus, the present study demonstrates that prenatal morphine exposure alters the HPA axis-regulated stress response and the sensitivity of negative feedback that are affected by the fluctuation of ovarian hormones.
Is Serum Ferritin an Additional Cardiovascular Risk Factor for All Postmenopausal Women?
Authors: Masse Priscilla G. , Dosy Juliana , Cole D.E.C. , Evroski J. , Allard Jacques , D’Astous Michel
Published: December 2004

Background: Most of the studies on cardiovascular disease (CVD) risk factors in menopause have focused on serum lipid(lipoprotein) abnormalities and were conducted in populations which were not well controlled for several important influential factors. Methods: Two homogenous groups of 30 apparently healthy Caucasian premenopausal women and 3–5 years postmenopausal women who were nonobese, nonsmoking and not using estrogen were compared in a well-controlled cross-sectional design. Fasting serum ferritin and plasma total homocysteine (tHcy) were evaluated concomitantly to classical serum lipid(lipoprotein) risk factors. Relationships between risk factors and the influence of other contributing variables such as diet and body weight were also examined. Results: Serum total cholesterol (p < 0.01), low-density lipoproteins (LDL; p < 0.05) and triglycerides (p < 0.05) of postmenopausal women were greater than that of their menstruating counterparts, even though they ate a CVD-preventive diet, had similar body weight and body fat distribution. Their serum ferritin was almost 3-fold greater (p < 0.0001) but was still within normal limits, except for the 38.5% of postmenopausal women who exhibited values above the 80 µg/l limit that has been associated with sharp increases in the rate of heart disease in either gender. Serum ferritin was low in one third of the postmenopausal group (as low as in the premenopausal control group, whose dietary iron intake was slightly below the nutritional recommendation). The mean plasma tHcy of the postmenopausal group was almost twice as elevated (p < 0.0001). Both ferritin and tHcy were found to be linked to serum cholesterol. The correlation between tHcy and triglycerides was also significant. Conclusion: Early menopause is not associated with blood iron overload and CVD risk factor in an important proportion of women.
Interactions between Nitric Oxide and Arachidonic Acid in Lung Epithelial Cells: Possible Roles for Peroxynitrite and Superoxide
Authors: Offer Sarit , Eliraz Abraham , Fink Gershon , Stark Aliza H. , Madar Zecharia
Published: December 2004

This study investigated interactions between nitric oxide synthesis and phospholipase A2 (PLA2) activation in lung epithelial cells. Nitrite formation, inducible nitric oxide synthase expression, and [3H]arachidonic acid (AA) release were determined following treatment with: (1) the nitric oxide synthase inhibitors NG-nitro-L-arginine methyl esther (L-NAME) and aminoguanidine; (2) arachidonyl trifluoromethyl ketone (AACOCF3), a specific cytosolic PLA2 inhibitor; (3) S-morpholinosydnonimine (SIN-1), a nitric oxide donor which provokes peroxynitrite formation; (4) trolox, a free radical scavenger, and (5) the AA release agonists calcium ionophore, phorbol 12-myristate 13-acetate, and sodium vanadate. The results demonstrated that (1) L-NAME and aminoguanidine inhibited agonist-induced AA release by 40 and 65%, respectively; (2) AACOCF3 inhibited nitrite formation and inducible nitric oxide synthase expression in a dose-dependent manner; (3) SIN-1, together with AA release agonists, significantly increased the AA output, and (4) trolox counteracted the SIN-1 effects. Our results demonstrate cross talk between nitric oxide synthase and PLA2 pathways, with a possible intermediary role for peroxynitrite and superoxide.
Neurovascular Decompression in Trigeminal Neuralgia: Role of Intraoperative Neurophysiological Monitoring in the Learning Period
Authors: Brock Stefano , Scaioli Vidmer , Ferroli Paolo , Broggi Giovanni
Published: December 2004

This paper deals with the first 45 consecutive patients undergoing microvascular decompression (MVD) surgery for trigeminal neuralgia, studied with perioperative brainstem auditory evoked potentials (BAEPs) and electromyography (EMG). We observed a good correlation between the intraoperative BAEP modifications and postoperative hearing function. BAEP monitoring was useful in identifying the manoeuvres that may compromise cochlear nerve function. This improved the surgical technique in the subsequent cases and reduced the incidence of iatrogenic hearing deficits after the learning period. There were no correlations between the entity of the intraoperative EMG discharges and the postoperative facial and trigeminal function. Intraoperative EMG monitoring can be useful during the period of learning as a means of identifying the different nerves in the cisternal tract.
Electrocardiographic Abnormalities as Predictors for Over-Range Lithium Levels
Authors: Hsu Chih-Hsin , Liu Ping-Yen , Chen Jyh-Hong , Yeh Tzung-Lieh , Tsai Hsiang-Yi , Lin Li-Jen
Published: December 2004

Background: Lithium compounds have been widely used in the treatment of manic-depressive illness. Several electrocardiogram (ECG) abnormalities, including ventricular arrhythmias, atrioventricular conduction abnormalities, T wave changes and QT interval prolongation, have been reported to be associated with lithium. However, the correlation between serum lithium levels and ECG changes has never been characterized in a systematic way. Methods: This retrospective study included 76 patients undergoing lithium treatment with available records of lithium levels. Eleven patients (4 men) had serum lithium levels >1.2 mEq/l and were diagnosed as lithium over range. Clinical characteristics and various ECG changes were analyzed in patients with and without lithium over range. Results: Patients with lithium over range had a slower heart rate and longer PR, QT and corrected QT (QTc) intervals. QTc interval >440 ms was more commonly found in patients with lithium over range (55 vs. 8%, p < 0.001). Similarly, diffuse T wave inversion was more commonly associated with lithium over range (73 vs. 17%, p < 0.001). The daily dosage of lithium was similar between patients with and without over-range lithium levels. When these two ECG changes were combined, the sensitivity and specificity in predicting lithium over range were 64 and 97%, respectively. These findings were independent of the concomitant use of β-blockers. Conclusions: QTc interval >440 ms and diffuse T wave inversion were significantly more common in patients with lithium over range, and were good predictors of lithium over range. More liberal checkup of the ECG in patients undergoing lithium treatment may be of help in the early detection of lithium over range.
Effects of HMG-CoA Reductase Inhibition on Hepatic Expression of Key Cholesterol-Regulatory Enzymes and Receptors in Nephrotic Syndrome
Authors: Vaziri Nosratola D. , Liang Kaihui
Published: December 2004

Background: Hypercholesterolemia is one of the major manifestations of nephrotic syndrome. We have previously shown that nephrotic hypercholesterolemia is associated with and, in part, due to dysregulation of hepatic HMG-CoA reductase, acyl-CoA:cholesterol acyltransferase (ACAT) and cholesterol 7α-hydroxylase, as well as lecithin:cholesterol acyltransferase (LCAT), low-density lipoprotein (LDL) receptor and high-density lipoprotein (HDL) receptor deficiencies. This study was carried out to discern the effect of inhibition of HMG-CoA reductase on expression of the key enzymes and receptors involved in cholesterol metabolism in the liver. Methods: Rats with puromycin-induced nephrotic syndrome were treated with either a statin (rosuvastatin 20 mg/kg/day) or placebo for 2 weeks. Placebo-treated normal rats served as controls. Gene expression, protein abundance and/or activities of relevant receptors and enzymes were quantified. Results: The untreated nephrotic rats showed heavy proteinuria, hypoalbuminemia, hypercholesterolemia, elevated total cholesterol:HDL cholesterol ratio and normal creatinine clearance. This was associated with severe reductions in hepatic LDL receptor, hepatic HDL receptor and plasma LCAT concentration, marked upregulation of hepatic ACAT, and unchanged cholesterol 7α-hydroxylase (rate-limiting step in cholesterol catabolism). Statin administration for 2 weeks ameliorated hepatic LDL receptor and HDL receptor deficiencies and significantly lowered plasma cholesterol, LDL cholesterol, total cholesterol:HDL cholesterol ratio and proteinuria. Conclusions: HMG-CoA reductase inhibition improved hepatic LDL and HDL receptor deficiencies, and ameliorated the associated hyperlipidemia in the nephrotic rats.
Clinicopathological Features Influencing Pelvic Lymph Node Metastasis and Vaginal and Parametrial Involvement in Patients with Carcinoma of the Cervix
Authors: Silva-Filho Agnaldo L. , Reis Fernando M. , Traiman Paulo , Pedrosa Moises S. , Miranda Dairton , Triginelli Sérgio A.
Published: December 2004

Purpose: This study was undertaken to evaluate clinical and pathologic findings that predicted pelvic lymph node metastasis and parametrial and vaginal involvement in patients with stage IB carcinoma of the cervix. Methods: 71 patients with diagnosis of stage IB (FIGO) cervical cancer were prospectively studied from December 1997 to August 2002. The patient’s age, clinical stage (IB1 or IB2), histological classification, grade of differentiation, tumor volume, and lymphatic vascular space invasion (LVSI) were evaluated. Statistical methods included χ2 test and Fisher’s exact test to evaluate significant differences between the groups. The level of significance was set at p < 0.05. Results: The clinical stage was IB1 in 51 patients (71.8%) and IB2 in 20 patients (28.2%). The histological classification identified squamous cell carcinoma in 60 patients (84.5%) and adenocarcinoma in 11 patients (15.5%). The average tumoral volume was 22.8 ± 24.3 cm3 (0.3–140.0 cm3). The tumor was well differentiated (G1) in 8 (11.3%), moderately differentiated (G2) in 40 (56.3%) and poorly differentiated in 23 (32.4%) of the cases. The presence of LVSI was detected in 14 patients (19.7%) and was associated with pelvic lymph node metastasis and vaginal and parametrial involvement (p = 0.002, p = 0.001 and p < 0.001; respectively). The average number of positive pelvic lymph nodes was significantly higher in the patients with LVSI compared with patients without LVSI (2.47 ± 2.8 vs. 0.33 ± 0.74; p = 0.001). There was no association of age, clinical stage, histological classification, grade of differentiation or tumor volume with pelvic lymph node metastasis and vaginal and parametrial involvement. Conclusion: The presence of LVSI is significantly associated with pelvic lymph node metastasis and vaginal and parametrial involvement in patients with stage IB cervical carcinoma.
Prostaglandin E Synthases in Zebrafish
Authors: Pini Barbara , Grosser Tilo , Lawson John A. , Price Tom S. , Pack Michael A. , FitzGerald Garret A.
Published: December 2004

Objective—

Prostaglandin E synthases (PGESs) are being explored as antiinflammtory drug targets as alternatives to cyclooxygenase (COX)-2. Located downstream of the cyclooxygenases, PGESs catalyze PGE
2
formation, and deletion of microsomal (m)-PGES-1 abrogates inflammation. We sought to characterize the developmental expression of COX and PGES in zebrafish.

Methods and Results—

We cloned zebrafish cytosolic (c) and m-PGES orthologs and mapped them to syntenic regions of chromosomes 23 and 5. cPGES was widely expressed during development and was coordinately regulated with zCOX-1 in the inner ear, the pronephros, and intestine. COX-2 and mPGES-1 exhibited restricted expression, dominantly in the vasculature of the aortic arch. However, the enzymes were anatomically segregated within the vessel wall. Experiments with antisense morpholinos and with nonsteroidal antiinflammatory drugs suggest that these genes may not be critical for development.

Conclusions—

mPGES-1 is developmentally coregulated with COX-2 in vasculature. Given the high fecundidity and translucency of the zebrafish, this model may afford a high throughput system for characterization of novel PGES inhibitors.
Targeting to C-Terminal Myosin Heavy Chain May Explain Mechanotransduction Involving Focal Adhesion Kinase in Cardiac Myocytes
Authors: Fonseca Priscila M. , Inoue Rosana Y. , Kobarg Claudia B. , Crosara-Alberto Daniella P. , Kobarg Jörg , Franchini Kleber G.
Published: December 2004

Focal adhesion kinase (Fak) has been implicated as a signaling molecule involved in the early response of cardiac myocytes to mechanical stress. The mechanism of Fak activation by mechanical stimuli is not clear. In this study, we report the load-induced Fak activation and its association with myosin heavy chain in cardiac myocytes. Pressure overload lasting from 3 to 60 minutes was shown to induce Fak phosphorylation at Tyr-397, -576/7, -861, and -925 as detected by phosphospecific antibodies. This was paralleled by increases of Fak/Src association and Src activity (Tyr-418 phosphorylation). Yeast two-hybrid screening of an adult rat cDNA library revealed an interaction between Fak and C-terminal coiled-coil region of α-myosin heavy chain. This was confirmed by pulldown assay with GST-C-terminal myosin fragment and native Fak from rat left ventricle. Such interaction was confirmed by coimmunoprecipitation assay with anti-Fak and anti-heavy chain cardiac myosin antibodies, confocal microscopy of double-labeled isolated cardiac myocytes and immunoelectron microscopy with anti-Fak antibody. Fak activation by mechanical stress was accompanied by a reduction of Fak/myosin heavy chain association and its relocation at subcellular sites such as costameres, Z-discs, and nuclei. Thus, our present data identify Fak interaction with C-terminal region of myosin heavy chain adding comprehensive data on Fak activation by mechanical stress and mechanotransduction in cardiac myocytes.
Postcarotid Endarterectomy Hyperperfusion or Reperfusion Syndrome
Authors: Karapanayiotides Theodoros , Meuli Reto , Devuyst Gerald , Piechowski-Jozwiak Bartlomiej , Dewarrat Annelise , Ruchat Patrick , Von Segesser Ludwig , Bogousslavsky Julien
Published: December 2004

Background and Purpose—

Hyperperfusion syndrome (HS) after carotid endarterectomy (CEA) has been related to impaired cerebrovascular autoregulation in a chronically hypoperfused hemisphere. Our aim was to provide new insight into the pathophysiology of the HS using magnetic resonance imaging (MRI) studies with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (PWI).

Methods—

Five out of 388 consecutive patients presented 2 to 7 days after CEA, partial seizures (n=5), focal deficits (n=5), and intracerebral hemorrhage (n=3). In 4 patients, using sequential examinations, we identified vasogenic or cytotoxic edema by DWI; we assessed relative interhemispheric difference (RID) of cerebral blood flow (CBF) by PWI; and we measured middle cerebral artery mean flow velocities (MCA Vm) by transcranial Doppler (TCD).

Results—

None of the patients presented pathological DWI hyperintensities, consistent with the absence of acute ischemia or cytotoxic edema. In 2 patients, we found an MRI pattern of reversible vasogenic edema similar to that observed in the posterior leukoencephalopathy syndrome. Middle cerebral artery (MCA) mean flow velocities (Vm) were not abnormally increased at any time. PWI documented a 20% to 44% RID of CBF in favor of the ipsilateral to CEA hemisphere.

Conclusions—

HS can occur in the presence of moderate relative hyperperfusion of the ipsilateral hemisphere. MCA Vm values may not accurately reflect RID of CBF over the cortical convexity. We suggest that the hemodynamic pathogenetic mechanisms of the HS are more complicated than hitherto believed and that they may be more accurately described by the term “reperfusion syndrome.”
Toll-like Receptor 4
Asp299Gly
Gene Polymorphism and Risk of Atherothrombosis
Authors: Zee Robert Y.L. , Hegener Hillary H. , Gould Jessica , Ridker Paul M.
Published: December 2004

Background and Purpose—

Recent findings of an association between a functional toll-like receptor 4 (
TLR4
) D299G gene variant and reduced risk of atherothrombotic disorders have generated great interest.

Methods—

We evaluated the TLR4 D299G polymorphism among 695 individuals with incident myocardial infarction (MI) or stroke and among 695 age- and smoking-matched individuals who remained free of reported cardiovascular disease during follow-up within the Physicians’ Health Study.

Results—

Overall, we observed little evidence of association between the D299G polymorphism and risk of any atherothrombotic event (
P
=0.25), incident MI (
P
=0.89), or stroke (
P
=0.09), assuming an additive model. Adjusting for traditional cardiovascular risk factors or assuming a dominant model yielded similar null findings. Whereas the observed carrier frequency of the D299G polymorphism in our data (13.0%) is consistent with those observed in most other studies, it was higher than the 6.8% carrier frequency observed in the initial study that suggested a protective effect for this gene variant. Thus, this former association may have been caused, in part, by an underestimation of the control frequency.

Conclusion—

In contrast to previous data, the D299G TLR4 polymorphism was not associated with risk of incident MI or stroke in this large prospective study of US men.
Low-Latitude Freshwater Influence on Centennial Variability of the Atlantic Thermohaline Circulation
Authors: Vellinga Michael , Wu Peili
Published: December 2004

Variability of the thermohaline circulation (THC) has been analyzed in a long control simulation by the Met Office's Third Hadley Centre Coupled Ocean–Atmosphere General Circulation Model (HadCM3). It is shown that internal THC variability in the coupled climate system is concentrated at interannual and centennial time scales, with the centennial mode being dominant. Centennial oscillations of the THC can impact surface climate via an interhemispheric SST contrast of 0.1°C in the Tropics and more than 0.5°C in mid- and high latitudes. A mechanism is proposed based on detailed process analysis involving large-scale air–sea interaction on multidecadal time scales. Anomalous northward ocean heat transport associated with a strong phase of the Atlantic THC generates a cross-equatorial SST gradient. This causes the ITCZ to move to a more northerly position with increased strength. The extra rainfall resulting from the anomalous ITCZ imposes a freshwater flux and produces a salinity anomaly in the tropical North Atlantic. Such sustained salinity anomalies slowly propagate toward the subpolar North Atlantic at a lag of 5–6 decades. The accumulated low-salinity water lowers upper-ocean density, which causes the THC to slow down. The oscillation then enters the opposite phase.
Characterizing Tropical Cirrus Life Cycle, Evolution, and Interaction with Upper-Tropospheric Water Vapor Using Lagrangian Trajectory Analysis of Satellite Observations
Authors: Luo Zhengzhao , Rossow William B.
Published: December 2004

Tropical cirrus evolution and its relation to upper-tropospheric water vapor (UTWV) are examined in the paper by analyzing satellite-derived cloud data, UTWV data from infrared and microwave measurements, and the NCEP–NCAR reanalysis wind field. Building upon the existing International Satellite Cloud Climatology Project (ISCCP) data and the Television and Infrared Observation Satellite (TIROS) Operational Vertical Sounder (TOVS) product, a global (except polar region), 6-hourly cirrus dataset is developed from two infrared radiance measurements at 11 and 12 μm. The UTWV is obtained in both clear and cloudy locations by developing a combined satellite infrared and microwave-based retrieval. The analysis in this study is conducted in a Lagrangian framework. The Lagrangian trajectory analysis shows that the decay of deep convection is immediately followed by the growth of cirrostratus and cirrus, and then the decay of cirrostratus is followed by the continued growth of cirrus. Cirrus properties continuously evolve along the trajectories as they gradually thin out and move to the lower levels. Typical tropical cirrus systems last for 19–30 ± 16 h. This is much longer than cirrus particle lifetimes, suggesting that other processes (e.g., large-scale lifting) replenish the particles to maintain tropical cirrus. Consequently, tropical cirrus can advect over large distances, about 600–1000 km, during their lifetimes. For almost all current GCMs, this distance spans more than one grid box, requiring that the water vapor and cloud water budgets include an advection term. Based on their relationship to convective systems, detrainment cirrus are distinguished from in situ cirrus. It is found that more than half of the tropical cirrus are formed in situ well away from convection. The interaction between cirrus and UTWV is explored by comparing the evolution of the UTWV along composite clear trajectories and trajectories with cirrus. Cirrus are found to be associated with a moister upper troposphere and a slower rate of decrease of UTWV. Moreover, the elevated UTWV has a longer duration than cirrus. The amount of water in cirrus is too small for evaporation of cirrus ice particles to moisten the upper troposphere significantly (but cirrus may be an important water vapor sink). Rather, it is likely that the same transient motions that produce the cirrus also transport water vapor upward to maintain a larger UTWV.
Global Occurrences of Extreme Precipitation and the Madden–Julian Oscillation: Observations and Predictability
Authors: Jones Charles , Waliser Duane E. , Lau K. M. , Stern W.
Published: December 2004

This study investigates 1) the eastward propagation of the Madden–Julian oscillation (MJO) and global occurrences of extreme precipitation, 2) the degree to which a general circulation model with a relatively realistic representation of the MJO simulates its influence on extremes, and 3) a possible modulation of the MJO on potential predictability of extreme precipitation events. The observational analysis shows increased frequency of extremes during active MJO phases in many locations. On a global scale, extreme events during active MJO periods are about 40% higher than in quiescent phases of the oscillation in locations of statistically significant signals.

A 10-yr National Aeronautics and Space Administration (NASA) Goddard Laboratory for the Atmospheres (GLA) GCM simulation with fixed climatological SSTs is used to generate a control run and predictability experiments. Overall, the GLA model has a realistic representation of extremes in tropical convective regions associated with the MJO, although some shortcomings also seem to be present. The GLA model shows a robust signal in the frequency of extremes in the North Pacific and on the west coast of North America, which somewhat agrees with observational studies. The analysis of predictability experiments indicates higher success in the prediction of extremes during an active MJO than in quiescent situations. Overall, the predictability experiments indicate the mean number of correct forecasts of extremes during active MJO periods to be nearly twice the correct number of extremes during quiescent phases of the oscillation in locations of statistically significant signals.
Global Warming and Western North Pacific Typhoon Activity from an Observational Perspective
Authors: Chan Johnny C. L. , Liu Kin Sik
Published: December 2004

Based on results from climate model simulations, many researchers have suggested that because of global warming, the sea surface temperature (SST) will likely increase, which will then lead to an increase in the intensity of tropical cyclones (TCs). This paper reports results of a study of the relationship between SST and observed typhoon activity (which is used as a proxy for the intensity of TCs averaged over a season) over the western North Pacific (WNP) for the past 40 yr. The average typhoon activity over a season is found to have no significant relationship with SST in the WNP but increases when the SST over the equatorial eastern Pacific Ocean is above normal. The mean annual typhoon activity is generally higher (lower) during an El Niño (La Niña) year. Such interannual variations of typhoon activity appear to be largely constrained by the large-scale atmospheric factors that are closely related to the El Niño–Southern Oscillation (ENSO) phenomenon. These large-scale dynamic and thermodynamic factors include low-level relative vorticity, vertical wind shear, and moist static energy. Such results are shown to be physically consistent with one another and with those from previous studies on the interannual variations of TC activity. The results emphasize the danger of drawing conclusions about future TC intensity based on current climate model simulations that are not designed to make such predictions.
Strong Trends in the Skill of the ERA-40 and NCEP–NCAR Reanalyses in the High and Midlatitudes of the Southern Hemisphere, 1958–2001*
Authors: Bromwich David H. , Fogt Ryan L.
Published: December 2004

The European Centre for Medium-Range Weather Forecasts (ECMWF) Re-Analysis (ERA-40) and the National Centers for Environmental Prediction–National Center for Atmospheric Research (NCEP–NCAR) reanalysis (NCEP1) data are compared with Antarctic and other mid- to high-latitude station observations for the complete years of overlap, 1958–2001. Overall, it appears that ERA-40 more closely follows the observations; however, a more detailed look at the presatellite era reveals many shortcomings in ERA-40, particularly in the austral winter.

By calculating statistics in 5-yr moving windows for June–July–August (JJA), it is shown that ERA-40 correlations with observed MSLP and surface (2 m) temperatures are low and even negative during the mid-1960s. A significant trend in skill in ERA-40 is observed in conjunction with the assimilation of satellite data during winter, eventually reaching a high level of skill after 1978 that is superior to NCEP1. NCEP1 shows consistency in its correlation with observations throughout time in this season; however, the biases in the NCEP1 MSLP fields decrease significantly with time. Similar problems are also found in the 500-hPa geopotential height fields above the direct influences of the mountainous topography. The height differences between ERA-40 and NCEP1 over the South Pacific are substantial before the modern satellite era throughout the depth of the troposphere. The ability for ERA-40 to be more strongly constrained by the satellite data compared to NCEP1, which is largely constrained by the station observational network, suggests that the differing assimilation schemes between ERA-40 and NCEP1 lead to the large discrepancies seen here. Thus, both reanalyses must be used with caution over high southern latitudes during the nonsummer months prior to the assimilation of satellite sounding data.
Violent Adolescence: State Development and the Propensity for Militarized Interstate Conflict
Authors: Boehmer Charles R. , Sobek David
Published: December 2004

This article examines how economic development influences interstate conflict. Rather than theorizing a linear relationship between economic development and state behavior in militarized conflicts, this article hypothesizes a non-linear relationship where both extreme poverty and prosperity reduce this risk. This occurs because states at an intermediate level of development have both the opportunity and willingness to pursue territorial claims, which makes them most prone to militarized interstate conflicts. The changing orientation of economies from agricultural and extractive activities eventually to service-based economies alters the cost–benefit calculations concerning territorial acquisition. Developed states, more reliant on services for their economic growth, are less likely to push territorial claims, decreasing their involvement in interstate conflict. Meanwhile, the poorest states, although they have more to gain through territorial expansion, have a decreased ability to pursue their objectives through military force. The authors examine all states between 1870 and 1992 at the monadic level of analysis. In general, the statistical analysis confirms the hypotheses. States at an intermediate level of development are most prone to initiate and participate in militarized conflicts, including those over the issue of territory and those that result in battlefield deaths. High levels of economic development mitigate the effects of military power and population growth that increase the risk of interstate violence. This project helps explain why past studies have linked development to both war and peace, as well as suggesting possible flashpoints in the future. Finally, the results also suggest that other models in the literature theorizing linear functions for economic development and conflict are misspecified.
Putting the Numbers to Work: Implications for Violence Prevention
Authors: DeRouen Karl R. , Goldfinch Shaun
Published: December 2004

By analysing international crisis behaviour from 1918 to 1994, this study seeks a better understanding of the factors that make interstate and intrastate crises endure and escalate into violence. Observations are crisis actors drawn from the International Crisis Behavior (ICB) dataset. The analysis indicates that an actor is more likely to use violence in a crisis if there is social unrest in that country; if it is contiguous to its main adversary in the crisis; if there is a violent trigger to the crisis; if there is an ethnic dimension to the crisis; and if the crisis is a long one. If the principal adversaries in a dyad are democratic or the actor is democratic, the likelihood of the use of violence is significantly reduced. Crises tend to be longer when there is an ethnic component and if there is violence. Taken together, the two analyses link crisis duration and outbreak of violence. Ethnicity and unrest have both direct and indirect effects on violence. The findings have implications for conflict prevention in two ways. If the factors found to be predictors of an escalation to violence are present during a crisis, then this provides an important early warning for agencies that the outbreak of violence is likely. In particular, early and decisive intervention, assuming it is successful, may be an effective method of preventing escalation to violence. Even in the absence of a crisis, the existence of such factors can be addressed through structural prevention, particularly through the development of democratic and other institutions.
War and Economic Performance
Authors: Koubi Vally
Published: December 2004

This article studies the consequences of inter-and intrastate wars for economic growth in a large cross-section of countries during the period 1960–89. It establishes that cross-country differences in economic growth are systematically related to the severity and duration of war. The combined prewar, contemporaneous, and postwar association between growth and war is negative; that is, economic performance has been lower in countries that fought a severe and/or prolonged war. However, the causal effect of war on postwar economic performance is positive. In particular, the longer or more severe the war, the higher the subsequent long-term rate of economic growth. A possible interpretation of these findings is that war is more likely to occur in poorly performing countries and/or to have a negative direct – contemporaneous – effect on growth. But in the longer term, war creates growth-enhancing possibilities. Interestingly, these effects arise mostly from civil wars and are quantitatively quite substantial. For instance, an increase in war duration by 10% leads to an increase of 2.1% in the average growth rate. The findings of this article are thus consistent with the predictions of the theories of both Organski & Kugler and Olson.