bluuebunny/crossref_metadata_2025_split huggingface dataset:
The extracellular regulated kinases (ERK) 1/2 mediate cannabinoid‐induced inhibition of gap junctional communication in endothelial cells
Authors: Brandes R P , Popp R , Ott G , Bredenkötter D , Wallner C , Busse R , Fleming I 
Published: January 2005

Cannabinoids are potent inhibitors of endothelium‐derived hyperpolarizing factor (EDHF)‐mediated relaxations. We set out to study the mechanism underlying this effect and the possible role of cannabinoid‐induced changes in intercellular gap junction communication.
In cultured endothelial cells, Δ9‐tetrahydrocannabinol (Δ9‐THC) and the cannabinoid receptor agonist HU210, increased the phosphorylation of extracellular regulated kinases 1/2 (ERK1/2) and inhibited gap junctional communication, as determined by Lucifer Yellow dye transfer and electrical capacity measurements.
Δ9‐THC elicited a pronounced increase in the phosphorylation of connexin 43, which was sensitive to PD98059 and U0126, two inhibitors of ERK1/2 activation. Inhibition of ERK1/2 also prevented the Δ9‐THC‐induced inhibition of gap junctional communication.
Δ9‐THC prevented both the bradykinin‐induced hyperpolarization and the nitric oxide and prostacyclin‐independent relaxation of pre‐contracted rings of porcine coronary artery. These effects were prevented by PD98059 as well as U0126.
In the absence of Δ9‐THC, neither PD98059 nor U0126 affected the NO‐mediated relaxation of coronary artery rings but both substances induced a leftward shift in the concentration – relaxation curve to bradykinin when diclofenac and Nωnitro‐L‐arginine were present. Moreover, PD98059 and U0126 prolonged the bradykinin‐induced hyperpolarization of porcine coronary arteries, without affecting the magnitude of the response.
These results indicate that the cannabinoid‐induced activation of ERK1/2, which leads to the phosphorylation of connexin 43 and inhibition of gap junctional communication, may partially account for the Δ9‐THC‐induced inhibition of EDHF‐mediated relaxation. Moreover, the activation of ERK1/2 by endothelial cell agonists such as bradykinin, appears to exert a negative feedback inhibition on EDHF‐mediated responses.

British Journal of Pharmacology (2002) 136, 709–716; doi:10.1038/sj.bjp.0704776
YC‐1 increases cyclo‐oxygenase‐2 expression through protein kinase G‐ and p44/42 mitogen‐activated protein kinase‐dependent pathways in A549 cells
Authors: Chang Ming‐Shyan , Lee Wen‐Sen , Teng Che‐Ming , Lee Horng‐Mo , Sheu Joen‐Rong , Hsiao George , Lin Chien‐Huang 
Published: January 2005

YC‐1, an activator of soluble guanylate cyclase (sGC), has been shown to increase the intracellular cGMP concentration. This study was designed to investigate the signaling pathway involved in the YC‐1‐induced COX‐2 expression in A549 cells.
YC‐1 caused a concentration‐ and time‐dependent increase in COX activity and COX‐2 expression in A549 cells. Pretreatment of the cells with the sGC inhibitor (ODQ), the protein kinase G (PKG) inhibitor (KT‐5823), and the PKC inhibitors (Go 6976 and GF10923X), attenuated the YC‐1‐induced increase in COX activity and COX‐2 expression.
Exposure of A549 cells to YC‐1 caused an increase in PKC activity; this effect was inhibited by ODQ, KT‐5823 or Go 6976. Western blot analyses showed that PKC‐α, ‐ι, ‐λ, ‐ζ and ‐μ isoforms were detected in A549 cells. Treatment of A549 cells with YC‐1 or PMA caused a translocation of PKC‐α, but not other isoforms, from the cytosol to the membrane fraction. Long‐term (24 h) treatment of A549 cells with PMA down‐regulated the PKC‐α.
The MEK inhibitor, PD 98059 (10–50 μM), concentration‐dependently attenuated the YC‐1‐induced increases in COX activity and COX‐2 expression. Treatment of A549 cells with YC‐1 caused an activation of p44/42 MAPK; this effect was inhibited by KT‐5823, Go 6976, long‐term (24 h) PMA treatment or PD98059, but not the p38 MAPK inhibitor, SB 203580.
These results indicate that in human pulmonary epithelial cells, YC‐1 might activate PKG through an upstream sGC/cGMP pathway to elicit PKC‐α activation, which in turn, initiates p44/42 MAPK activation, and finally induces COX‐2 expression.

British Journal of Pharmacology (2002) 136, 558–567; doi:10.1038/sj.bjp.0704777
NO‐ and haem‐independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle
Authors: Stasch Johannes‐Peter , Schmidt Peter , Alonso‐Alija Cristina , Apeler Heiner , Dembowsky Klaus , Haerter Michael , Heil Markus , Minuth Torsten , Perzborn Elisabeth , Pleiss Ulrich , Schramm Matthias , Schroeder Werner , Schröder Henning , Stahl Elke , Steinke Wolfram , Wunder Frank 
Published: January 2005

Soluble guanylyl cyclase (sGC) is the only proven receptor for the ubiquitous biological messenger nitric oxide (NO) and is intimately involved in many signal transduction pathways, most notably in regulating vascular tone and platelet function. sGC is a heterodimeric (α/ß) protein that converts GTP to cyclic GMP; NO binds to its prosthetic haem group. Here, we report the discovery of a novel sGC activating compound, its interaction with a previously unrecognized regulatory site and its therapeutic implications.
Through a high‐throughput screen we identified BAY 58‐2667, an amino dicarboxylic acid which potently activates sGC in an NO‐independent manner. In contrast to NO, YC‐1 and BAY 41‐2272, the sGC stimulators described recently, BAY 58‐2667 activates the enzyme even after it has been oxidized by the sGC inhibitor ODQ or rendered haem deficient.
Binding studies with radiolabelled BAY 58‐2667 show a high affinity site on the enzyme.
Using photoaffinity labelling studies we identified the amino acids 371 (α‐subunit) and 231 – 310 (ß‐subunit) as target regions for BAY 58‐2667.
sGC activation by BAY 58‐2667 results in an antiplatelet activity both in vitro and in vivo and a potent vasorelaxation which is not influenced by nitrate tolerance.
BAY 58‐2667 shows a potent antihypertensive effect in conscious spontaneously hypertensive rats. In anaesthetized dogs the hemodynamic effects of BAY 58‐2667 and GTN are very similar on the arterial and venous system.
This novel type of sGC activator is a valuable research tool and may offer a new approach for treating cardiovascular diseases.

British Journal of Pharmacology (2002) 136, 773–783; doi:10.1038/sj.bjp.0704778
Ultrastructure of spermiogenesis and the spermatozoon in Castrada cristatispina Papi, 1951 (Platyhelminthes, Rhabdocoela, Typhloplanida)
Authors: Culioli Julia‐Laurence , Foata Joséphine , Mori Christophe , Orsini Antoine , Marchand Bernard 
Published: January 2005

AbstractSpermiogenesis in Castrada cristatispina begins with the formation of a zone of differentiation containing two centrioles with associated striated rootlets and an intercentriolar body between them. The centrioles give rise to two parallel, free flagella of the Trepaxonemata 9 + ‘1’ pattern, growing out in opposite directions. Spermatids undergo a latero‐ventral rotation of the flagella and a subsequent disto‐proximal rotation of centrioles, and a distal cytoplasmic projection appears. The former rotation involves the compression of a row of microtubules and allows the recognition of a ventral side and a dorsal side. At the end of the differentiation, the centrioles and cortical microtubules lie parallel to the sperm axis. The modifications of the intercentriolar body and the migration of the nucleus and the centrioles toward the distal projection are described. The mature spermatozoon of C. cristatispina is filiform, tapered at both ends and shares several features with the other Rhabdocoela gametes. Nevertheless, the posterior extremity is capped by an electron‐dense material. A gradient between mitochondria and dense bodies exists along the sperm axis. This study has enable us a phylogenetic approach of the Rhabdocoela through a comparison of the ultrastructural features of C. cristatispina with the other Rhabdocoela taxa. We propose the disto‐proximal rotation of centrioles as a synapomorphy of the Rhabdocoela.
Comparative analysis of the sperm ultrastructure of three species of Phyllomedusa (Anura, Hylidae)
Authors: Costa G. C. , Garda A. A. , Teixeira R. D. , Colli G. R. , Báo S. N. 
Published: January 2005

AbstractWe describe the sperm ultrastructure of three species of frogs in the genus Phyllomedusa. According to micrographs, total size of the spermatozoon of Phyllomedusa hypochondrialis is significantly smaller than those of Phyllomedusa bicolor and Phyllomedusa tarsius. The acrosome complex consists of two conical structures covering the nucleus, the acrosome vesicle and the subacrosomal cone. The subacrosomal cone of P. bicolor and P. tarsius is less electron‐dense and appears more granular in transverse section than in P. hypochondrialis. In P. bicolor and P. tarsius, the nuclear space is reduced and the subacrosomal cone fills most of the space between the acrosome vesicle and nucleus. The anterior region of the nucleus in the spermatozoa of P. bicolor and P. tarsius ends abruptly, while in P. hypochondrialis it is sharp‐ended. In P. bicolor and P. tarsius, the axial fibre is much larger than in P. hypochondrialis. The sperm ultrastructure of Phyllomedusa appears conservative at the intrageneric level. Future studies on the sperm ultrastructure of hylids can provide new insights on the systematics of the group and a larger database for a cladistic analysis.
2. Freud's ‘id’ and Jung's ‘self’ as aids in self‐analysis
Authors: Plaut Alfred B. J. 
Published: January 2005

Abstract:  The id and the self are described as constructs of our unconscious which can be deployed in describing the analytic process. They can be used like the x in mathematics or the joker in a pack of cards as fitting in almost anywhere. But we can call on them as important aids to concentration, when additional room is made for meditating on the past which then comes to life again. They are useful for analysing ourselves and others. In this way the id as well as the self become aide‐mémoires. The analysis of the repressed by means of the transference is not the only road to hitherto unconscious memories.This kind of meditation has helped me despite all reservations to undertake self‐analysis and to write an autobiography. I maintain that one can have a transference to oneself. It is, of course, narcissistic. But then, no one can write an autobiography without a healthy dose of narcissism.
Development of the pelvis and posterior part of the vertebral column in the Anura
Authors: Ročková Hana , Roček Zbyněk 
Published: January 2005

AbstractThe anuran pelvic girdle is unique among all amphibians in that its acetabular portion is located far posterior to the sacrum, lateral to the postsacral (= caudal) vertebral column, which is reduced to a single rod‐like element called the urostyle. This situation in the adult is strikingly different not only from that in ancestral temnospondyls but also in other modern amphibians. Because there is no fossil that would document this evolutionary anatomical modification except for Triadobatrachus, the only data may be inferred from development in modern anurans. We chose seven anuran species (belonging to the genera Discoglossus, Bombina, Pelobates, Bufo, Rana and Xenopus), representing the principal locomotory types (saltation, swimming, crawling and burrowing). Development of the pelvic girdle was studied on cleared and stained whole mounts and partly on serial histological sections. The basic developmental pattern was similar in all species: the pelvis on both sides develops from two centres (puboischiadic and iliac, respectively). The ilium then extends vertically towards the sacral vertebra and later rotates posteriorly so that ultimately the acetabulum is lateral to the tail (= urostyle). Only minor deviations from this pattern were found, mainly associated with differences in water and terrestrial dwelling.
Traversing the intact/fibrillated joint surface: a biomechanical interpretation
Authors: Broom Neil D. , Ngo Thuy , Tham Evelyn 
Published: January 2005

AbstractCartilage taken from the osteoarthritic bovine patellae was used to investigate the progression of change in the collagenous architecture associated with the development of fibrillated lesions. Differential interference contrast optical microscopy using fully hydrated radial sections revealed a continuity in the alteration of the fibrillar architecture in the general matrix consistent with the progressive destructuring of a native radial arrangement of fibrils repeatedly interconnected in the transverse direction via a non‐entwinement‐based linking mechanism. This destructuring is shown to occur in the still intact regions adjacent to the disrupted lesion thus rendering them more vulnerable to radial rupture. Two contrasting modes of surface rupture were observed and these are explained in terms of the absence or presence of a skewed structural weakening of the intermediate zone. A mechanism of surface rupture initiation based on simple bi‐layer theory is proposed to account for the intensification of surface ruptures observed in the intact regions on advancing towards the fibrillation front. Focusing specifically on the primary collagen architecture in the cartilage matrix, this study proposes a pathway of change from intact to overt disruption within a unified structural framework.
Mosquito transmission modulates the immune response in mice infected with the L3 of Brugia pahangi
Authors: Gillan Victoria , Devaney Eileen 
Published: January 2005

SUMMARY Mice infected by syringe inoculation with the L3 of the filarial nematode Brugia pahangi generate a strong Th2 response. In this study we compared immune responses in mice infected via syringe with those infected by mosquito transmission of L3. Levels of antigen‐specific IL‐4, IL‐5 and IL‐10 were significantly reduced in mice infected via mosquito. A possible explanation of these results was that mice infected via mosquito received fewer L3 than those infected via syringe. To investigate this possibility, mice were infected with different numbers of L3 (50, 25 or 10). Howere there was no difference in responses in these animals, suggesting that the reduced immune reactivity in mice infected by mosquito cannot be solely ascribed to exposure to lower numbers of parasites. These results also demonstrate that the L3 is an extremely potent stimulus for Th2 differentiation, with 10 L3 sufficient to drive a strong Th2 response. The differences in immune reactivity between syringe and mosquito infected mice may relate to the presence of immuno‐suppressive factors in mosquito saliva inoculated at the time of transmission or may reflect the interaction of L3 with different populations of antigen presenting cells in the two groups of mice. Further studies will be required to differentiate between these possibilities.
Schistosomiasis co‐infection in humans influences inflammatory markers in uncomplicated Plasmodium falciparum malaria
Authors: Diallo T. O. , Remoue F. , Schacht A. M. , Charrier N. , Dompnier J.‐P. , Pillet S. , Garraud O. , N'Diaye A. A. , Capron A. , Capron M. , Riveau G. 
Published: January 2005

SUMMARY Malaria and schistosomiasis are the two major parasite diseases present in developing countries. The epidemiological co‐infection with schistosomiasis could influence the development of the physiological reaction associated with Plasmodium falciparum infection in human. Most studies have demonstrated the association of circulating levels of interferon‐γ (IFN‐γ), tumour necrosis factor‐a (TNF‐α), interleukin‐10 (IL‐10), transforming growth factor (TGF‐β) and soluble Tumour Necrosis Factor Receptors (sTNF‐RI and sTNF‐RII) with the morbidity of malaria. In the present study, we showed that Schistosoma haematobium co‐infection influences, in an age‐dependent manner, the unbalance between pro‐ and anti‐inflammatory circulating cytokines that play a key role during malaria infection. Indeed, children co‐infected by S. haematobium have higher levels of IFN‐γ and sTNF‐RII than children infected only by P. falciparum. In contrast, co‐infected adults presented a significant increase of IFN‐γ, IL‐10, TGF‐β, sTNF‐RI and sTNF‐RII rates and IL‐10/TNF‐α ratio. Taken together, this study indicates that schistosomiasis co‐infection can unbalance the regulation of inflammatory factors in uncomplicated P. falciparum malaria. The possible consequences of the schistosomiasis co‐infection for age‐dependent malaria morbidity are discussed.
Gene cloning, expression and vaccine testing of Schistosoma japonicum SjFABP
Authors: Liu J. M. , Cai X. Z. , Lin J. J. , Fu Z. Q. , Yang G. Z. , Shi F. H. , Cai Y. M. , Shen W. , Taylor M. G. , Wu X. F. 
Published: January 2005

SUMMARY A 600 bp DNA fragment was amplified by PCR from an adult Schistosoma japonicum cDNA library. Sequence analysis confirmed that this fragment contained an S. japonicum Chinese mainland strain fatty acid binding protein (Sj14FABP) gene. This gene was subsequently expressed in Escherichia coli (E. coli) and in Baculovirus/silkworm systems. The recombinant protein from E. coli was a 41 kDa GST fusion protein (rSj14/GST), which could be purified by glutathione agarose affinity chromatography, with a yield of 25 mg/L E. coli culture. The recombinant protein from the Baculovirus/silkworm system was an 18 kDa fusion protein (rSj14/His), which could be purified by Ni‐NTA resin chromatography column with a yield of 3·5 mg per silkworm larva. Both rSj14/GST and rSj14/His could be recognized by S. japonicum‐infected mouse sera and anti‐rSj14/GST mouse sera in Western blotting. The purified recombinant protein was immunogenic in mice, rats and sheep, and 34·3%, 31·9% and 59·2% worm reductions, respectively, were obtained in vaccinated Kunming mice, Wistar rats and sheep vaccinated with Sj14/GST, compared to non‐vaccinated control groups. Worm reductions of 48·8% and 49·0% were recorded in Balb/c mice immunized with Sj14/His, compared to non‐vaccinated and BCG‐vaccinated groups, respectively. These results indicate that rSj14FABP is a promising candidate vaccine for schistosomiasis japonica, particularly as in the rat and sheep vaccination experiments, no adjuvant was used.
Unintentional methadone‐related overdose death in New Mexico (USA) and implications for surveillance, 1998–2002
Authors: Shah Nina , Lathrop Sarah L. , Landen Michael G. 
Published: January 2005

ABSTRACTAims  To determine death rates from methadone over time, to characterize methadone‐related death and to discuss public health surveillance of methadone‐related death.Design  We analyzed medical examiner data for all unintentional drug overdose deaths in New Mexico, USA, between 1998 and 2002.Measurements  Age‐adjusted death rates for methadone‐related death, logistic regression models for likelihood of methadone‐related death among all unintentional drug overdose deaths and bivariate comparisons within methadone‐related death.Findings  Of 1120 drug overdose deaths during this period, there were 143 (12.8%) methadone‐related deaths; the death rate decreased over the time period, averaging 1.6 per 100 000. Of 143 methadone‐related deaths, 22.4% were due to methadone alone, 23.8% were due to methadone/prescription drugs (no illicit drugs), 50.3% were due to methadone/illicit drugs and 3.5% were due to methadone/alcohol. These groups were significantly different in demographics, health history and circumstances of death. Of 79 decedents (55.2%) with a known source of methadone, 68 obtained methadone through a physician prescription (31 for methadone maintenance treatment (MMT), 27 for managing pain and 10 had unknown reason for prescription).Conclusions  Methadone‐related death rates and the proportion of methadone‐related death among all drug overdose deaths decreased in New Mexico from 1998 to 2002. It is important for surveillance of methadone‐related death to assess multiple drug causes, not just underlying cause. Also, methadone for pain management must be examined alongside MMT and when possible, methadone co‐intoxication should be described in the context of other drugs causing death.
Cut‐off levels for breath carbon monoxide as a marker for cigarette smoking
Authors: Javors Martin A. , Hatch John P. , Lamb Richard J. 
Published: January 2005

ABSTRACTAims  Current clinical studies often use a breath carbon monoxide (BCO) cut‐off level of 8 parts per million (p.p.m.) or higher to identify smoking. In this study, the cut‐off level of BCO as an indicator of smoking over the past 24 hours was re‐examined.Design  BCO and self‐reported smoking were obtained each weekday for up to 14 weeks in 213 subjects paid to deliver reduced BCO values. Analysis of 12 386 paired values for reported smoking and BCO were analyzed.Findings  The 25% quartile, median and 75% quartile values for BCO were 1, 1 and 2 p.p.m. on non‐smoking days and 2, 5 and 12 p.p.m. on smoking days, respectively. Receiver‐operating characteristic (ROC) analysis indicated that BCO provided high diagnostic accuracy to distinguish between smoking and non‐smoking days [area under the curve (AUC) = 0.853, P < 0.0001]. The highest combined sensitivity and specificity was observed at a BCO cut‐off level of 3 p.p.m. (sensitivity = 71.5%; specificity = 84.8%). At a BCO cut‐off of 8 p.p.m. sensitivity and specificity were 40.6% and 98.2%, respectively, indicating that many smokers would be falsely classified as abstinent. Finally, the percentage of true tests (positive and negative) was highest at a BCO cut‐off of 2 p.p.m. (80.2%).Conclusions  BCO cut‐off levels well below 8 p.p.m and as low as 2–3 p.p.m. may be more useful when it is important to maximize identification of smoking abstinence with a high degree of certainty.
The assessment of craving: psychometric properties, factor structure and a revised version of the Alcohol Craving Questionnaire (ACQ)
Authors: Raabe Almut , Grüsser Sabine M. , Wessa Michèle , Podschus Jan , Flor Herta 
Published: January 2005

ABSTRACTAims  The goal of the present study was to examine the psychometric properties and factor structure of the Alcohol Craving Questionnaire (ACQ).Design and participants  The German version of the ACQ was administered to a sample of 243 alcohol‐dependent or alcohol‐abusing subjects. A subgroup of the sample (n = 46) completed the German translation of the Obsessive Compulsive Drinking Scale (OCDS) and the ACQ a second time.Measurements  To validate the factor models, confirmatory factor analyses (CFA) were carried out. Examination of the psychometric properties of the ACQ included the analysis of the item characteristics to exclude non‐sensitive items, an exploratory factor analysis of the remaining items and calculation of internal consistency, test–retest reliability and convergent validity.Findings  Neither of the two models showed a satisfactory correspondence. An exploratory factor analysis of a revised version of the ACQ (ACQ‐R), based on the psychometric properties of the items, revealed two stable factors (‘urge and intention to drink alcohol’ and ‘reinforcement’) with high internal consistency, test–retest reliability and convergent validity. The model fit was also excellent in the CFA.Conclusions  The ACQ‐R is a reliable and valid instrument to assess alcohol craving. However, the ACQ‐R lacks items related to loss of control. Therefore a multi‐dimensional assessment, e.g. the combination of the ACQ‐R and the OCDS, is recommended.