bluuebunny/crossref_metadata_2025 huggingface dataset:
Science and Community Psychology: Social Norms for Pluralistic Inquiry
Authors: Kelly James G.
Published: June 2003

The concept of “science” linked to the concept of “community psychology” requires adaptation. In the case of community psychology, science is public to citizens as well as to the scientist. The community psychologist, as scientist, works from the expectation that choices of topics, methods, and interpretation of findings are done in concert with representatives of the community. The following remarks offer 7 ways to keep vital the research of the community psychologist while contributing to robust and useful knowledge.
Musikalische und mimische Emotionserkennung: Eine Pilotstudie mit psychiatrischen Patienten
Authors: Busch Veronika , Nickel Anne Kathrin , Hillecke Thomas K. , Gross Tanjef , Meißner Nicole , Bolay Hans Volker
Published: June 2003

Zusammenfassung. Dargestellt wird eine kontrollierte explorative Pilotstudie mit acht Patienten einer psychiatrischen Tagesklinik zur Erkennung von grundlegenden Gefühlsqualitäten (u.a. Freude, Trauer, Ärger) in Mimik und Musik 1 Wir danken dem Psychiatrischen Zentrum Nordbaden (PZN) für die Unterstützung bei der Durchführung dieser Pilotstudie. . Die Studie untersucht, ob sich Unterschiede in der Erkennungsleistung zwischen mimisch und musikalisch dargestellten Emotionen ergeben und ob die Emotionserkennung zwischen psychiatrischen Patienten und gesunden Probanden differiert. Die Messung der mimischen Emotionserkennung wurde mit dem computer-gestützten FEEL-Test 2 Wir danken Professor Dr. H. C. Traue für die freundliche Genehmigung zur Verwendung des FEEL-Tests. erhoben, während für die musikalische Erkennung von Gefühlsqualitäten in Anlehnung an den FEEL-Test ein neuer Test entwickelt wurde. Beide Testinstrumente werden vorgestellt sowie erste Ergebnisse diskutiert.
Musik- und Tanztherapie in der ambulanten Rehabilitation Drogenabhängiger
Authors: Arnold Oliver
Published: June 2003

Zusammenfassung. Musik- und Tanztherapie sind in der ambulanten Rehabilitation Drogenabhängiger hierzulande kaum bekannte Therapieformen. Es wird daher ein Konzept dazu vorgestellt, das auf breiter Erfahrung in einer ambulanten Suchtberatungsstelle in Baden-Württemberg beruht.
Die phänomenologische Bilderfassung: Ein kunsttherapeutisches Instrument
Authors: Stuhler-Bauer Angela , Elbing Ulrich
Published: June 2003

Zusammenfassung. Dieser Artikel stellt ein kunsttherapeutisches Instrument zur Bildbeschreibung auf phänomenologischer Basis vor. Das methodische Vorgehen in der Entwicklung und in der Handhabung des Instruments geht vom Begriff des ästhetischen Zustands aus, der in den Rahmen des phänomenologischen Erkenntniszugangs eingebettet wird. Die einzelnen Beschreibungskriterien des Instruments werden aus diesem Hintergrund hergeleitet und begründet. Die Erarbeitung dieses Instruments durch Stuhler-Bauer (2001) ist Bestandteil einer Forschungsstrategie zur Entwicklung valider Instrumente kunsttherapeutischer Bilderfassung, die einleitend kurz vorgestellt wird.
Analogie als Kernkonzept der Musiktherapie
Authors: Smeijsters Henk
Published: June 2003

Zusammenfassung. Der Artikel unterscheidet zwischen metaphorisch und psychologisch fundierter Analogie in der Musiktherapie. Bei einer metaphorischen Analogie werden Phänomene miteinander verglichen, die ihrem Wesen nach verschieden sind. Bei einer psychologischen Analogie geht es um die Gleichheit psychischer und musikalischer Prozesse. Die psychologische Analogie wird an Hand der Gleichheit der grundlegenden Parameter der psychischen und musikalischen Muster, wie sie Daniel Stern ausgearbeitet hat, begründet. Quantitative und qualitative Forschungen zeigen, dass Analogie sowohl die Grundlage in der Arbeit von Musiktherapeuten verschiedener Schulen und verschiedener Arbeitsfelder als auch in der Erfahrung von Klienten während der Musiktherapie formt. Das Analogiekonzept wird einem Vergleich mit anderen Konzepten wie Homologie, Isomorphie, und dynamic form unterzogen. Eine ausführliche abschließende Definition gibt eine detallierte psychologische Erklärung der Wirkung der Musiktherapie durch Analogie.
A Model-Based Approach to the Quantitative Analysis of Eyeblink EMG Response Components
Authors: Blumenthal Terry D. , Melkonian Dmitriy
Published: June 2003

Abstract A recently developed method of fragmentary decomposition (FD) of nonstationary physiological signals was extended to eyeblink EMG measurement to quantify all significant stimulus-induced components and identify their parameters. FD provides a representation of single-trial eyeblink EMG as a nonstationary signal with the generic mass potential (GMP) being the universal functional element. The current study uses this model-based signal-processing methodology to identify distinct stimulus-induced components of eyeblink EMG and to extract additional psychophysiological information from the eyeblink signal. Analysis of the single-trial eyeblink EMG records from 10 normal subjects showed that GMP is an adequate functional element of which an eyeblink EMG response is composed. In particular, both spontaneous and stimulus-induced single components of eyeblink EMG are produced by functionally similar mechanisms. However, we found that about 54% of GMPs are combined into complex patterns that respond differently to various experimental conditions. To typify characteristic patterns of eyeblink EMG component composition, we defined two fundamental categories of components: Complex components (CC), comprised of multiple subcomponents (GMPs), versus monolithic components (MC), involving a single GMP. Given the nonstationary character of eyeblink EMG, the stimulus-related appearance of some specific component patterns, such as MCs and CCs, is in essence a probabilistic problem. To characterize the probabilistic structure of eyeblink EMG, we introduce the stimulus dependent probability diagram (SDPD), which shows the probability of appearance of defined component patterns of EMG activity at different times after the stimulus presentation. SDPD analysis shows that the stimulus elicits strong though short-term (phasic) effects on monolithic components and moderate but long-lasting (tonic) effects on complex components.
Scaled P300 Scalp Distribution Correlates of Verbal Deception in an Autobiographical Oddball Paradigm: Control for Task Demand
Authors: Rosenfeld J. Peter , Rao Archana , Soskins Matthew , Miller Antoinette Reinhart
Published: June 2003

Abstract Subjects participated in two trial blocks of an autobiographical oddball paradigm. In the first block, 14% of the stimuli were the subject's phone number, 86% were other, meaningless numbers. Subjects responded yes or no, verbally and truthfully. In the second block, stimuli were dates, and the oddball was the subject's birthdate. Subjects again responded verbally, but dishonestly on about 50% of the trials and truthfully on the other 50%. Reaction times differed between the first and the second blocks, but not between the honest and dishonest trials of the second block. P300 amplitude was reduced in dishonest trials of the second block. Honest trials of both blocks had similar P300 amplitudes. Scaled scalp distributions were the same for honest trials of both blocks, but differed between honest and dishonest trials of the second block. There were no latency effects. The results are discussed from the viewpoint that task demand effects do not mediate the P300 differences between honest and dishonest responses.
P50 Gating is Not Affected by Selective Attention
Authors: Kho Kuan H. , Verkes Robbert J. , Eling Paul , Zwarts Machiel J. , Ellenbroek Bart , van Luijtelaar Gilles
Published: June 2003

Abstract The influence of selective attention on P50 gating - the decline of the amplitude of the P50 component of the auditory evoked potential (AEP) to the second of a pair of clicks - was examined. Three conditions were presented in counterbalanced order to 29 healthy volunteers: a baseline condition, in which the double click was presented and no specific task was required, an attention condition in which attention to the clicks was required, and a distraction condition in which paired clicks were presented during rehearsal time of a reversed digit span task. P50 gating, as measured with ratio and difference scores, did not differ across the three conditions. However, the amplitude of the N100 showed an increase in the attention condition compared to the two nonattention conditions, supporting the validity of our task manipulations. The data on P50 demonstrate that P50 gating is not affected by attentional manipulations.
Protein kinase C‐α attenuates cholinergically stimulated gastric acid secretion of rabbit parietal cells
Authors: Fährmann Michael , Kaufhold Marc , Pfeiffer Andreas F , Seidler Ursula
Published: June 2003

The phorbolester 12‐O‐tetradecanoyl phorbol‐13‐acetate (TPA), an activator of protein kinase C (PKC), inhibits cholinergic stimulation of gastric acid secretion. We observed that this effect strongly correlated with the inhibition of Ca2+/calmodulin‐dependent protein kinase II (CaMKII) activity in rabbit parietal cells.

The aim of this study was to specify the function of PKC‐α in cholinergically stimulated H+ secretion. PKC‐α represents the only calcium‐dependent PKC isoenzyme that has been detected in rabbit parietal cells.

Gö 6976, an inhibitor of calcium‐dependent PKC, concentration‐dependently antagonized the inhibitory effect of TPA, and, therefore, revealed the action of PKC‐α on carbachol‐induced acid secretion in rabbit parietal cells.

TPA exerted no additive inhibition of carbachol‐stimulated acid secretion if acid secretion was partially inhibited by the potent CaMKII inhibitor 1‐[N,O‐bis(5‐isoquinolinsulfonyl)‐N‐methyl‐L‐tyrosyl]‐4‐phenyl‐piperazine (KN‐62).

Since both kinase modulators, TPA and KN‐62, affected no divergent signal transduction pathways in the parietal cell, an in vitro model has been used to study if PKC directly targets CaMKII. CaMKII purified from parietal cell‐containing gastric mucosa of pig, was transphosphorylated by purified cPKC containing PKC‐α up to 1.8 mol Pi per mol CaMKII in vitro. The autonomy site of CaMKII was not transphosphorylated by PKC.

The phosphotransferase activity of the purified CaMKII was in vitro inhibited after transphosphorylation by PKC if calmodulin was absent during transphosphorylation. Attenuation of CaMKII activity by PKC showed strong similarity to the downregulation of CaMKII by basal autophosphorylation.

Our results suggest that PKC‐α and CaMKII are closely functionally linked in a cholinergically induced signalling pathway in rabbit parietal cells. We assume that in cholinergically stimulated parietal cells PKC‐α transinhibits CaMKII activity, resulting in an attenuation of acid secretion.

British Journal of Pharmacology (2003) 139, 545–554. doi:10.1038/sj.bjp.0705211
Development of agonists of endothelin‐1 exhibiting selectivity towards ETA receptors
Authors: Langlois Chantal , Létourneau Myriam , Lampron Philipe , St‐Hilaire Véronique , Fournier Alain
Published: June 2003

Endothelin‐1 (ET‐1) is a bicyclic 21‐amino‐acid peptide causing a potent and sustained vasoconstriction, mainly through the ETA receptor subtype. So far, no selective ETA agonists are described in the literature.

A series of truncated and chemically modified ET‐1 analogues were obtained through solid‐phase peptide synthesis and their biological activity was assessed on rat thoracic aorta rings (ETA receptors) and guinea‐pig lung parenchyma strips (ETB receptors).

Structure–activity studies led to the identification of ET‐1 fragments exhibiting an ETA selective agonistic activity.

In particular, [D‐Lys9]cyclo11–15 ET‐1(9–21) was the most potent peptide. It appeared as a full agonist of ETA receptors, being under two orders of magnitude less potent than ET‐1 (EC50: 2.3 × 10−7 vs 6.8 × 10−9 M). Interestingly, even a linear formylated analogue, [Ala11,15, Trp(For)21]ET‐1(9–21), showed a selective ETA activity (EC50: 3.0 × 10−6 M). None of the numerous analogues of the series exhibited substantial effects in the guinea‐pig lung parenchyma bioassay.

Thus, this study describes the first compounds showing a significant bioactivity in an ETA pharmacological preparation while being inactive in an ETB paradigm. They show that the ET‐1 pharmacophores, responsible for the ETA‐mediated actions, are located within the 9–21 segment of the molecule. Moreover, the bicyclic structure of ET‐1 does not appear as essential for the ETA‐related vasoconstriction. Results also suggest that the positive charge of the Lys9 side chain participates in an intramolecular ionic bond with the carboxylate function of Asp18.

British Journal of Pharmacology (2003) 139, 616–622. doi:10.1038/sj.bjp.0705252
Functional involvement of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP‐sensitive K+ channels
Authors: Yunoki Takakazu , Teramoto Noriyoshi , Ito Yushi
Published: June 2003

We have investigated the possible roles of sulphonylurea receptor (SUR) type 1 and 2B in the activity of pig urethral ATP‐sensitive K+ channels (KATP channels) by use of patch‐clamp and reverse transcriptase–polymerase chain reaction (RT–PCR) techniques.

In voltage‐clamp experiments, not only diazoxide, a SUR1 and weak SUR2B activator, but also pinacidil, a selective SUR2 activator, caused an inward current at a holding potential of −50 mV in symmetrical 140 mM K+ conditions.

Gliclazide (1 μM), a selective SUR1 blocker, inhibited the 10 μM pinacidil‐induced currents (Ki=177 μM) and the 500 μM diazoxide‐induced currents (high‐affinity site, Ki1=5 nM; low‐affinity site, Ki2=108 μM) at −50 mV.

Application of tolbutamide (100 μM) reversibly caused an inhibition of the 500 μM diazoxide‐induced current at –50 mV.

MCC‐134, a SUR type‐specific KATP channel regulator (1–100 μM), produced a concentration‐dependent inward K+ current, which was suppressed by the application of glibenclamide at −50 mV. The amplitude of the MCC‐134 (100 μM)‐induced current was approximately 50% of that of the 100 μM pinacidil‐induced currents.

Using cell‐attached configuration, MCC‐134 activated a glibenclamide‐sensitive KATP channel which was also activated by pinacidil.

RT–PCR analysis demonstrated the presence of SUR1 and SUR2B transcripts in pig urethra.

These results indicate that both SUR1 and SUR2B subunits play a functional role in regulating the activity of pig urethral KATP channels and that SUR1 contributes less than 25% to total KATP currents.

British Journal of Pharmacology (2003) 139, 652–660. doi:10.1038/sj.bjp.0705268
Chronic cardiotoxicity of anticancer anthracyclines in the rat: role of secondary metabolites and reduced toxicity by a novel anthracycline with impaired metabolite formation and reactivity
Authors: Sacco Giuseppe , Giampietro Rossella , Salvatorelli Emanuela , Menna Pierantonio , Bertani Nicoletta , Graiani Gallia , Animati Fabio , Goso Cristina , Maggi Carlo A , Manzini Stefano , Minotti Giorgio
Published: June 2003

The anticancer anthracycline doxorubicin (DOX) causes cardiomyopathy upon chronic administration. There is controversy about whether DOX acts directly or after conversion to its secondary alcohol metabolite DOXol. Here, the role of secondary alcohol metabolites was evaluated by treating rats with cumulative doses of DOX or analogues – like epirubicin (EPI) and the novel disaccharide anthracycline MEN 10755 – which were previously shown to form less alcohol metabolites than DOX when assessed in vitro.

DOX induced electrocardiographic and haemodynamic alterations, like elongation of QαT or SαT intervals and suppression of isoprenaline‐induced dP/dt increases, which developed in a time‐dependent manner and were accompanied by cardiomegaly, histologic lesions and mortality. EPI caused less progressive or severe effects, whereas MEN 10755 caused essentially no effect.

DOX and EPI exhibited comparable levels of cardiac uptake, but EPI formed ∼60% lower amounts of its alcohol metabolite EPIol at 4 and 13 weeks after treatment suspension (P<0.001 vs DOX). MEN 10755 exhibited the lowest levels of cardiac uptake; hence, it converted to its alcohol metabolite MEN 10755ol ∼40% less efficiently than did EPI to EPIol at either 4 or 13 weeks. Cardiotoxicity did not correlate with myocardial levels of DOX or EPI or MEN 10755, but correlated with those of DOXol or EPIol or MEN 10755ol (P=0.008, 0.029 and 0.017, respectively).

DOX and EPI inactivated cytoplasmic aconitase, an enzyme containing an Fe–S cluster liable to disassembly induced by anthracycline secondary alcohol metabolites. DOX caused greater inactivation of aconitase than EPI, a finding consistent with the higher formation of DOXol vs EPIol. MEN 10755 did not inactivate aconitase, which was because of both reduced formation and impaired reactivity of MEN 10755ol toward the Fe–S cluster. Aconitase inactivation correlated (P<0.01) with the different levels of cardiotoxicity induced by DOX or EPI or MEN 10755.

These results show that (i) secondary alcohol metabolites are important determinants of anthracycline‐induced cardiotoxicity, and (ii) MEN 10755 is less cardiotoxic than DOX or EPI, a behaviour attributable to impaired formation and reactivity of its alcohol metabolite.

British Journal of Pharmacology (2003) 139, 641–651. doi:10.1038/sj.bjp.0705270
Endothelium‐dependent relaxation and endothelial hyperpolarization by P2Y receptor agonists in rat‐isolated mesenteric artery
Authors: Mistry Hammit , Gitlin Jonathan M , Mitchell Jane A , Hiley C Robin
Published: June 2003

Vasorelaxation and hyperpolarization of endothelial cells by adenosine 5′‐[β‐thio]diphosphate (ADPβS) and adenosine 5′‐[γ‐thio]triphosphate (ATPγS) were studied in rat‐isolated mesenteric artery. Effects from stimulation of P2X receptors were avoided by desensitization with α,β‐methylene adenosine triphosphate.

ADPβS caused concentration‐ and endothelium‐dependent relaxations of methoxamine‐precontracted small (third generation) and main mesenteric artery. These were inhibited by Nω‐nitro‐L‐arginine methyl ester (L‐NAME) or a combination of apamin plus charybdotoxin (inhibitors of Ca2+‐activated K+ channels); L‐NAME, apamin and charybdotoxin applied together abolished the response.

ATPγS induced limited relaxation (35% of methoxamine‐induced tone at 10 μM) of small mesenteric artery, which was sensitive to L‐NAME or endothelium denudation. However, it almost completely relaxed the main mesenteric artery over an extended concentration range (>6 orders of magnitude) in an endothelium‐dependent manner. This relaxation was inhibited by either L‐NAME or a combination of apamin with charybdotoxin, and abolished by a combination of all the three inhibitors.

The P2Y1 receptor antagonist MRS 2179 (2′‐deoxy‐N6‐methyladenosine 3′,5′‐bisphosphate; 0.3–3 μM) caused parallel rightward shifts of the concentration/relaxation curve to ADPβS (pA2=7.1). However, MRS 2179 did not inhibit, but potentiated, relaxant responses to ATPγS. MRS 2179 did not affect the contractile responses ATPγS in small mesenteric artery; ATPγS did not contract the main mesenteric artery.

ADPβS hyperpolarized the endothelium of the main mesenteric artery in a concentration‐dependent manner. This was unaffected by L‐NAME but antagonized by MRS 2179. ATPγS also hyperpolarized the mesenteric artery endothelium in a concentration‐dependent manner but, when ATPγS was applied at 10 μM, its effect was potentiated by MRS 2179 (3 μM).

It is concluded that both relaxation and hyperpolarization to ADPβS are mediated by P2Y1 receptors and that the endothelial hyperpolarization is related to the L‐NAME‐resistant relaxation. Relaxation to the P2Y2 agonist ATPγS shows regional variation along the mesenteric vasculature. The mechanisms for potentiation of relaxation and hyperpolarization by ATPγS are unknown, but may indicate interactions between P2Y receptor subtypes.

British Journal of Pharmacology (2003) 139, 661–671. doi:10.1038/sj.bjp.0705271
Involvement of nitric oxide and tachykinins in the effects induced by protease‐activated receptors in rat colon longitudinal muscle
Authors: Mulè Flavia , Baffi Maria Carmela , Capparelli Anna , Pizzuti Roberta
Published: June 2003

The aim of the present study was to verify a possible involvement of nitric oxide (NO) and of tachykinins in the contractile and relaxant effects caused by the activation of protease‐activated receptor (PAR)‐1 and PAR‐2 in the longitudinal muscle of rat colon.

Mechanical responses to the PAR‐1 activating peptides, SFLLRN‐NH2 (10 nM–10 μM) and TFLLR‐NH2 (10 nM–10 μM), and to the PAR‐2‐activating peptide, SLIGRL‐NH2 (10 nM–10 μM), were examined in vitro in the absence and in the presence of different antagonists.

The relaxation induced by SFLLRN‐NH2, TFLLR‐NH2 and SLIGRL‐NH2 was antagonised by the inhibitor of NO synthase L‐Nω‐nitroarginine methyl ester (300 μM), or by the inhibitor of the guanylyl cyclase, 1‐H‐oxodiazol‐[1,2,4]‐[4,3‐a]quinoxaline‐1‐one (10 μM).

The contractile responses to PAR‐1 and PAR‐2 activation were concentration‐dependently attenuated by SR140333 (0.1–1 μM), NK1 receptor antagonist, or by SR48968 (0.1–1 μM), NK2 receptor antagonist. The combined pretreatment with SR140333 (1 μM) and SR48968 (1 μM) produced additive suppressive effects on the contractile responses to PAR activation. Pretreatment of the preparation with capsaicin (10 μM) markedly reduced the contractions evoked by SFLLRN‐NH2, TFLLR‐NH2 and SLIGRL‐NH2, while ω‐conotoxin GVIA (0.2 μM) had no effect.

The present results suggest that in rat colonic longitudinal muscle, PAR‐1 and PAR‐2 activation can evoke (i) relaxation through the production of NO or (ii) contraction through the release of tachykinins, likely, from sensory nerves. These actions may contribute to motility disturbances during intestinal trauma and inflammation.

British Journal of Pharmacology (2003) 139, 598–604. doi:10.1038/sj.bjp.0705273
Bisphenol A diglycidyl ether‐induced apoptosis involves Bax/Bid‐dependent mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and Smac/DIABLO
Authors: Fehlberg Sebastian , Gregel Cornelia M , Göke Alexandra , Göke Rüdiger
Published: June 2003

Bisphenol A diglycidyl ether (BADGE) is a peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) antagonist, which is able to induce apoptosis in tumor cells independently of PPAR‐γ in caspase‐dependent and ‐independent manners. Additionally, BADGE promotes TRAIL‐induced apoptosis.

We report that BADGE activates via Bax and caspases‐2 and ‐8 both the intrinsic and extrinsic apoptotic pathways using Bid as a shunt.

BADGE stimulates the mitochondrial release of apoptosis‐inducing factor (AIF), cytochrome c and second mitochondria‐derived activator of caspase/direct IAP‐binding protein with low pl (Smac/DIABLO). The release of cytochrome c could not be blocked by inhibitors of caspases‐3, ‐8 and ‐9 indicating that BADGE acts upstream of caspases‐3 and ‐9 and does not involve caspase‐8 to release cytochrome c.

While the caspase‐independent apoptotic effect might be mediated by AIF, the sensitizing effect of BADGE against other apoptotic substances is most likely mediated by the X‐linked inhibitor of apoptosis inhibitor Smac/DIABLO.

Our data suggest that BADGE or BADGE derivatives could represent promising substances for the treatment of neoplasms improving the antitumoral activity of TRAIL.

British Journal of Pharmacology (2003) 139, 495–500. doi:10.1038/sj.bjp.0705275
Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: a novel role of prostaglandins
Authors: von Banchet Gisela Segond , Scholze Anita , Schaible Hans‐Georg
Published: June 2003

Peripheral inflammation causes an increase in the proportion of primary afferent neurones that express neurokinin1 (NK1) receptors for substance P (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory pain. The aim of this study was to identify endogenous mediators that stimulate upregulation of NK1 receptors in dorsal root ganglion (DRG) neurones. Cultured DRG neurones from the adult normal rat were exposed for 2 days to media that contained specific mediators, namely potassium in high concentration, prostaglandin E2 (PGE2), somatostatin (SRIF), and compounds influencing second messenger cascades. After fixation neurones were labelled with an NK1 receptor antibody.

Repetitive addition of the inflammatory mediator PGE2 or dibutyryl‐cyclic adenosine 3′,5′ monophophate (db‐cAMP) to the culture medium enhanced the proportion of neurones with NK1 receptor‐like immunoreactivity from about 12% up to 40%. PGE2‐induced upregulation was prevented by coadministration of PGE2 and a protein kinase A inhibitor or SRIF to the medium. High potassium concentration, protein kinase C inhibitors and omission of nerve growth factor from the medium had no effect.

In calcium‐imaging experiments, bath application of SP evoked increases of the intracellular calcium concentration in about 20% of the neurones. This proportion increased to about 40% after PGE2‐pretreatment, but the increase was prevented when PGE2 and SRIF were coadministered to the medium.

These data show that the expression of NK1 receptor‐like immunoreactivity in DRG neurones is regulated by the inflammatory mediator PGE2. This upregulation depends on the intracellular adenylyl cyclase–protein kinase A pathway.

British Journal of Pharmacology (2003) 139, 672–680. doi:10.1038/sj.bjp.0705278
Endothelium‐independent relaxation to cannabinoids in rat‐isolated mesenteric artery and role of Ca2+ influx
Authors: Vanessa Ho W ‐S , Robin Hiley C
Published: June 2003

Three cannabinoid receptor agonists, anandamide (CB1 receptor‐selective) and the aminoalkyl‐indoles, JWH 015(2‐methyl‐1‐propyl‐1H‐indol‐3‐yl)‐1‐napthalenylmethanone; (CB2 receptor‐selective), R‐(+)‐WIN 55,212‐2 (R‐(+)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolol[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐napthalenylmethanone; slightly CB2 receptor‐selective), as well as the enantiomer S‐(−)‐WIN 55,212‐3(S‐(−)‐[2,3‐dihydro‐5‐methyl‐3‐(4‐morpholinylmethyl)pyrrolol[1,2,3‐de]‐1,4‐benzoxazin‐6‐yl]‐1‐napthalenylmethanone; inactive at cannabinoid receptors), induced endothelium‐independent relaxation of methoxamine‐precontracted isolated small mesenteric artery of rat. KCL (60 mM) precontraction did not affect relaxation to the aminoalkylindoles, but reduced that to anandamide.

SR14176A (N‐(piperidin‐1‐yl)‐5‐(4‐chlorophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide; 3 μM; CB1 receptor antagonist) inhibited relaxation only to JWH 015 and anandamide. Neither AM 251 (N‐(piperidin‐1‐yl)‐5‐(4‐iodophenyl)‐1‐(2,4‐dichlorophenyl)‐4‐methyl‐1H‐pyrazole‐3‐carboxamide; CB1 antagonist) nor SR 144528 (N‐[(1S)‐endo‐1,3,3‐trimethyl bicyclo[2.2.1] heptan‐2‐yl]‐5‐(4‐chloro‐3‐methylphenyl)‐1‐(4‐methylbenzyl)‐pyrazole‐3‐carboxamide; CB2 antagonist; both at 3 μM) affected any of the relaxations.

Vanilloid receptor desensitisation with capsaicin reduced anandamide relaxation; addition of SR 141716A (3 μM) then caused further inhibition. SR 141716A did not affect capsaicin‐induced relaxation.

The aminoalkylindoles inhibited CaCl2‐induced contractions in methoxamine‐stimulated vessels previously depleted of intracellular Ca2+. These inhibitory effects were greatly reduced or abolished in ionomycin‐(a calcium ionophore) contracted vessels. Anandamide also caused vanilloid receptor‐independent, SR 141716A‐ (3 μM) insensitive, inhibition of CaCl2 contractions.

In conclusion, the aminoalkylindoles JWH 015, R‐(+)‐WIN 55,212‐2 and S‐(−)‐WIN 55,212‐3 relax rat small mesenteric artery mainly by inhibiting Ca2+ influx into vascular smooth muscle. Anandamide causes vasorelaxation by activating vanilloid receptors, but may also inhibit Ca2+ entry. Relaxation to JWH 015 and anandamide was sensitive to SR 141716A, but there is no other evidence for the involvement of CB1 or CB2 receptors in responses to these compounds.

British Journal of Pharmacology (2003) 139, 585–597. doi:10.1038/sj.bjp.0705280
Growth hormone secretagogues modulate the electrical and contractile properties of rat skeletal muscle through a ghrelin‐specific receptor
Authors: Pierno Sabata , Luca Annamaria De , Desaphy Jean‐François , Fraysse Bodvael , Liantonio Antonella , Didonna Maria Paola , Lograno Marcello , Cocchi Daniela , Smith Roy G , Camerino Diana Conte
Published: June 2003

Growth hormone secretagogues (GHS) exhibit potent growth hormone (GH)‐releasing activity through the activation of a pituitary receptor. Here, we consider the possibility that GHS can target a specific receptor in rat skeletal muscle and have a role in the control of muscle function.

By means of the intracellular microelectrode technique, we found that in vitro application of hexarelin and L‐163,255 dose dependently reduced resting chloride (gCl) and potassium (gK) conductances in rat skeletal muscle. These effects were prevented by the GHS‐receptor antagonist [D‐Lys‐3]‐GHRP‐6, and by either phospholipase C or protein kinase C (PKC) inhibitors. Ghrelin, a natural ligand of GHS receptors, also induced a reduction of muscle gCl and gK, which was antagonised by [D‐Lys‐3]‐GHRP‐6.

Both GHS shifted the mechanical threshold for the contraction of muscle fibres towards more negative voltages. Accordingly, by means of FURA‐2 fluorescent measurements, we demonstrated that L‐163,255 induced a resting [Ca2+]i increase, which was reversible and not blocked by nifedipine or removal of external Ca2+.

Ageing is a condition characterised by a deficit of GH secretion, which in turn modifies the electrical and contractile properties of skeletal muscle. In contrast to GH, chronic treatment of aged rats with hexarelin or L‐163,255 failed to restore the electrical and contractile muscle properties. Moreover, the two GHS applied in vitro were able to antagonise the beneficial effect on gCl and gK obtained through chronic treatment of aged animals with GH.

Thus, skeletal muscle expresses a specific GHS receptor able to decrease gCl and gK through a PKC‐mediated intracellular pathway. This peripheral action may account for the lack of restoration of skeletal muscle function in long‐term GHS‐treated aged animals.

British Journal of Pharmacology (2003) 139, 575–584. doi:10.1038/sj.bjp.0705284
Heteroexchange of purines in the hippocampus: mixing‐up or messing‐up ATP and adenosine
Authors: Cunha Rodrigo A
Published: June 2003

British Journal of Pharmacology (2003) 139, 473–474. doi:10.1038/sj.bjp.0705286
Effects of G‐protein‐specific antibodies and Gβγ subunits on the muscarinic receptor‐operated cation current in guinea‐pig ileal smooth muscle cells
Authors: Yan H ‐D , Okamoto H , Unno T , Tsytsyura Ya D , Prestwich S A , Komori S , Zholos A V , Bolton T B
Published: June 2003

The effects on the whole‐cell carbachol‐induced muscarinic cationic current (mIcat) of antibodies against the α‐subunits of various G proteins, as well as the effect of a Gβγ subunit, were studied in single guinea‐pig ileal smooth muscle cells voltage‐clamped at −50 mV. Ionized intracellular calcium concentration, [Ca2+]i, was clamped at 100 nM using a 1,2‐bis(2‐aminophenoxyl‐ethane‐N,N,N′,N′‐tetraacetic acid)/Ca2+ mixture.

Application of ascending concentrations of carbachol (1–300 μM) activated mIcat (mean amplitude 0.83 nA at 300 μM carbachol; EC50 8 μM; Hill slope 1.0). A 20 min or longer intracellular application via the pipette solution of Gi3/Go or Go antibodies resulted in about a 70% depression of the maximum response without change in the EC50 value. In contrast, antibodies against α‐subunits of Gi1, Gi1/Gi2, Gi3, Gq/G11 or Gs protein over a similar or longer period did not significantly reduce mIcat. Antibodies to common Gβ or infusion of the Gβγ subunit itself had no effect on mIcat.

If cells were exposed briefly to carbachol (50 or 100 μM) at early times (<3 min) after infusion of antibodies to Gαi3/Gαo or to Gαo had begun, carbachol responses remained unchanged even after 20–60 min; that is, the depression of mIcat by these antibodies was prevented.

These data show that Gαo protein couples the muscarinic receptor to the cationic channel in guinea‐pig ileal longitudinal smooth muscle and that Gβγ is not involved. They also show that prior activation of the muscarinic receptor presumably causes a long‐lasting postactivation change of the G protein, which is not reflected in mIcat, but acts to hinder antibody binding.

British Journal of Pharmacology (2003) 139, 605–615. doi:10.1038/sj.bjp.0705289
Thermotoga neapolitana adenylate kinase is highly active at 30 degreesC
Authors: VIEILLE Claire , KRISHNAMURTHY Harini , HYUN Hyung-Hwan , SAVCHENKO Alexei , YAN Honggao , ZEIKUS J. Gregory
Published: June 2003

The adenylate kinase (AK) gene from Thermotoga neapolitana, a hyperthermophilic bacterium, was cloned and overexpressed in Escherichia coli, and the recombinant enzyme was biochemically characterized. The T. neapolitana AK (TNAK) sequence indicates that this enzyme belongs to the long bacterial AKs. TNAK contains the four cysteine residues that bind Zn2+ in all Gram-positive AKs and in a few other Zn2+-containing bacterial AKs. Atomic emission spectroscopy and titration data indicate a content of 1 mol of Zn2+/mol of recombinant TNAK. The EDTA-treated enzyme has a melting temperature (Tm=93.5 °C) 6.2 °C below that of the holoenzyme (99.7 °C), identifying Zn2+ as a stabilizing feature in TNAK. TNAK is a monomeric enzyme with a molecular mass of approx. 25 kDa. TNAK displays Vmax and Km values at 30 °C identical with those of the E. coli AK at 30 °C, and displays very high activity at 80 °C, with a specific activity above 8000 units/mg. The unusually high activity of TNAK at 30 °C makes it an interesting model to test the role of enzyme flexibility in activity.
Cloning and expression of biologically active Plantago lanceolata pollen allergen Pla l 1 in the yeast Pichia pastoris
Authors: CALABOZO Belén , DÍAZ-PERALES Araceli , SALCEDO Gabriel , BARBER Domingo , POLO Florentino
Published: June 2003

The glycoprotein Pla l 1 is the major allergen from English plantain (Plantago lanceolata) pollen, which is a common cause of pollinosis in temperate areas. Three complete cDNAs for Pla l 1 isoforms were isolated by PCR using specific 3′ and 5′ primers. All three Pla l 1 cDNAs code for a 25-residue leader peptide and a 131-residue mature protein that contains two polymorphic positions, an N-glycosylation site at position 107 and six cysteine residues involved in three disulphide bridges. The allergen variant Pla l 1.0101 was produced in Pichia pastoris at a yield of 20 mg per litre of culture as a mixture of non-glycosylated (17 kDa), glycosylated (23 kDa) and dimeric (32–39 kDa) forms. Recombinant Pla l 1 (rPla l 1) was purified by affinity chromatography with an anti-natural Pla l 1 (anti-nPla l 1) monoclonal antibody, and its molecular and immunological properties were compared with the natural allergen by CD spectroscopic analysis, enzymic deglycosylation, lectin-binding assay, immunodetection and ELISA-inhibition assays using sera from plantain-allergic patients. The recombinant allergen is properly folded, as deduced from CD spectra, and the immunodominant allergenic epitopes of the natural allergen are preserved in rPla l 1. These results allow us to conclude that P. pastoris is a convenient system for the efficient production of biologically active rPla l 1, which could have a potential use for clinical purposes. Furthermore, a sequence similarity of Pla l 1 to the major allergen from the olive tree pollen, Ole e 1, is revealed in this work, and the allergenic cross-reactivity between both allergens has been studied.
c-Myc potentiates the mitochondrial pathway of apoptosis by acting upstream of apoptosis signal-regulating kinase 1 (Ask1) in the p38 signalling cascade
Authors: DESBIENS Katia M. , DESCHESNES Réna G. , LABRIE Mireille M. , DESFOSSÉS Yan , LAMBERT Herman , LANDRY Jacques , BELLMANN Kerstin
Published: June 2003

Cell transformation by growth-promoting oncoproteins renders cells extremely sensitive to apoptosis through an unknown mechanism affecting the mitochondrial pathway of apoptosis. We have shown previously that sensitization to apoptosis also correlated with the activation of the stress-activated protein kinase p38. In the present study, we investigated the role of p38 in c-Myc-dependent apoptosis induced by the anticancer agent cisplatin. Cisplatin treatment of Rat1 cells with deregulated expression of c-Myc resulted in nuclear fragmentation that was accompanied in all cells by the activation of Bax and the translocation of cytochrome c from the mitochondria to the cytoplasm. None of these features of apoptosis was induced in control Rat-1 cells. p38 was also activated by cisplatin only in cells with deregulated expression of c-Myc, but, in contrast with all features of apoptosis, this activation was not affected by Bcl-2. Remarkably, overexpression of an interfering mutant of the p38α isoform, but not p38β, blocked cisplatin-induced Bax activation or cytochrome c release and nuclear fragmentation. Analysis of the kinase cascade upstream of p38 revealed a c-Myc-dependent activation by cisplatin of mitogen-activated protein kinase kinase (MKK) 3/6 and apoptosis signal-regulating kinase 1 (Ask1). Inhibition of Ask1 blocked p38 activation by cisplatin and all features of apoptosis. Several of these data were confirmed using other DNA-damaging agents. The findings indicated that c-Myc potentiation of the mitochondrial pathway of apoptosis results, at least in part, from a sensitization of Ask1 activation, allowing DNA-damaging agents to induce in cascade Ask1, p38α and Bax.
Hormonal regulation of the human sterol 27-hydroxylase gene CYP27A1
Authors: ARAYA Zufan , TANG Wanjin , WIKVALL Kjell
Published: June 2003

The mitochondrial sterol 27-hydroxylase (CYP27A1) is a multifunctional cytochrome P450 enzyme that catalyses important hydroxylations in the biosynthesis of bile acids and bioactivation of vitamin D3. Previous results [Babiker, Andersson, Lund, Xiu, Deeb, Reshef, Leitersdorf, Diczfalusy and Björkhem (1997) J. Biol. Chem. 272, 26253–26261] suggest that CYP27A1 plays an important role in cholesterol homoeostasis and affects atherogenesis. In the present study, the regulation of the human CYP27A1 gene by growth hormone (GH), insulin-like growth factor-1 (IGF-1), dexamethasone, thyroid hormones and PMA was studied. HepG2 cells were transfected transiently with luciferase reporter gene constructs containing DNA fragments flanking the 5′-region of the human CYP27A1 gene. GH, IGF-1 and dexamethasone increased the promoter activity by 2–3-fold, whereas thyroxine (T4) and PMA repressed the activity significantly when measured with luciferase activity expressed in the cells. The endogenous CYP27A1 enzyme activity in the cells was stimulated by GH, IGF-1 and dexamethasone, whereas T4 and PMA inhibited the activity. Experiments with progressive deletion/luciferase reporter gene constructs indicated that the response elements for GH may be localized in a region upstream to position −1094 bp. The putative response elements for dexamethasone were mapped to positions between −792 and −1095 bp. The −451 bp fragment of the human CYP27A1 gene was found to confer the activation by IGF-1, and the inhibition by T4 and PMA. Results of the present study suggest that CYP27A1 is regulated in human cells by hormones and signal-transduction pathways.
Identification of S1 proteins B2, C1 and D1 as AUF1 isoforms and their major role as heterogeneous nuclear ribonucleoprotein proteins
Authors: INOUE Akira , ARAO Yukitomo , OMORI Akira , ICHINOSE Sachiyo , NISHIO Koji , YAMAMOTO Naoki , KINOSHITA Yosihiro , MITA Shiro
Published: June 2003

AUF1 (A+U-rich RNA binding factor) participates in the rapid decay of mRNAs in the cytoplasm. It is sometimes called heterogeneous nuclear ribonucleoprotein (hnRNP) D0; however, evidence for its characterization as an hnRNP protein has been scarce. S1 proteins A–D are those selectively extracted at pH 4.9 from isolated nuclei pretreated with either RNase A or DNase I. In the present study we identified S1 (‘first supernatant’) proteins B2, C1 and D1 with p45, p40 and p37 AUF1s respectively, by microsequencing and product analysis of transfected cDNAs. We found, further, that more than 96% of the S1 proteins occurred in the nucleus, and localized largely in RNase-sensitive structures. B2 was confined in the nucleus and C1 directly bound to heterogeneous nuclear RNAs (hnRNAs). These B2 and C1 proteins formed hnRNP structures responsible for the 33 S, and, to lesser extent, the 40 S particles, which were liberated upon mild nucleolytic cleavage. On the other hand, D1 and the remainder of C1 were associated with nuclease-hypersensitive sites of hnRNAs, and comprised the major cytoplasmic AUF1s that may be involved in mRNA decay. Two-dimensional immunoblotting resolved each S1 isoform into up to six spots or more, and suggested that the previous uncertain relationship of hnRNP D0 and hnRNP D is resolved in terms of charge differences and differential splicing arising from one gene. The present results thus indicate that S1 proteins B2, C1 and D1 are identical with AUF1 proteins, but largely occur as hnRNP proteins in the nucleus. That hnRNP D0 is indeed an hnRNP protein was verified.
N-Acetylglutamate and its changing role through evolution
Authors: CALDOVIC Ljubica , TUCHMAN Mendel
Published: June 2003

N-Acetylglutamate (NAG) fulfils distinct biological roles in lower and higher organisms. In prokaryotes, lower eukaryotes and plants it is the first intermediate in the biosynthesis of arginine, whereas in ureotelic (excreting nitrogen mostly in the form of urea) vertebrates, it is an essential allosteric cofactor for carbamyl phosphate synthetase I (CPSI), the first enzyme of the urea cycle. The pathway that leads from glutamate to arginine in lower organisms employs eight steps, starting with the acetylation of glutamate to form NAG. In these species, NAG can be produced by two enzymic reactions: one catalysed by NAG synthase (NAGS) and the other by ornithine acetyltransferase (OAT). In ureotelic species, NAG is produced exclusively by NAGS. In lower organisms, NAGS is feedback-inhibited by l-arginine, whereas mammalian NAGS activity is significantly enhanced by this amino acid. The NAGS genes of bacteria, fungi and mammals are more diverse than other arginine-biosynthesis and urea-cycle genes. The evolutionary relationship between the distinctly different roles of NAG and its metabolism in lower and higher organisms remains to be determined. In humans, inherited NAGS deficiency is an autosomal recessive disorder causing hyperammonaemia and a phenotype similar to CPSI deficiency. Several mutations have been recently identified in the NAGS genes of families affected with this disorder.
Topology of the Erwinia chrysanthemi oligogalacturonate porin KdgM
Authors: PELLINEN Teijo , AHLFORS Helena , BLOT Nicolas , CONDEMINE Guy
Published: June 2003

The Erwinia chrysanthemi oligogalacturonate-specific monomeric porin, KdgM, does not present homology with any porins of known structure. A model of this protein, based on sequence similarity and the amphipathy profile, was constructed. The model depicts a β-barrel composed of 14 antiparallel β-strands. The accuracy of this model was tested by the chemical labelling of cysteine residues introduced by site-directed mutagenesis. The protein has seven surface-exposed loops. They are rather small with the exception of one, loop L6. Deletion of this loop allowed the entry of maltopentaose into the bacteria, a molecule too large to enter through the wild-type KdgM. Loop L6 could fold back into the lumen of the pore and play the role of the constriction loop L3 of general porins. With 14 transmembrane segments, the KdgM porin family could represent the smallest porin characterized to date.
Variation in the pH-dependent pre-steady-state and steady-state kinetic characteristics of cysteine-proteinase mechanism: evidence for electrostatic modulation of catalytic-site function by the neighbouring carboxylate anion
Authors: HUSSAIN Syeed , PINITGLANG Surapong , BAILEY Tamara S. F. , REID James D. , NOBLE Michael A. , RESMINI Marina , THOMAS Emrys W. , GREAVES Richard B. , VERMA Chandra S. , BROCKLEHURST Keith
Published: June 2003

The acylation and deacylation stages of the hydrolysis of N-acetyl-Phe-Gly methyl thionoester catalysed by papain and actinidin were investigated by stopped-flow spectral analysis. Differences in the forms of pH-dependence of the steady-state and pre-steady-state kinetic parameters support the hypothesis that, whereas for papain, in accord with the traditional view, the rate-determining step is the base-catalysed reaction of the acyl-enzyme intermediate with water, for actinidin it is a post-acylation conformational change required to permit release of the alcohol product and its replacement in the catalytic site by the key water molecule. Possible assignments of the kinetically influential pKa values, guided by the results of modelling, including electrostatic-potential calculations, and of the mechanistic roles of the ionizing groups, are discussed. It is concluded that Asp161 is the source of a key electrostatic modulator (pKa 5.0±0.1) in actinidin, analogous to Asp158 in papain, whose influence is not detected kinetically; it is always in the ‘on’ state because of its low pKa value (2.8±0.06).
Post-synaptic density-95 promotes calcium/calmodulin-dependent protein kinase II-mediated Ser847 phosphorylation of neuronal nitric oxide synthase
Authors: WATANABE Yasuo , SONG Tao , SUGIMOTO Katsuyoshi , HORII Mariko , ARAKI Nobukazu , TOKUMITSU Hiroshi , TEZUKA Tohru , YAMAMOTO Tadashi , TOKUDA Masaaki
Published: June 2003

Post-synaptic density-95 (PSD-95) is a neuronal scaffolding protein that associates with N-methyl-d-aspartate (NMDA) receptors and links them to intracellular signalling molecules. In neurons, neuronal nitric oxide synthase (nNOS) binds selectively to the second PDZ domain (PDZ2) of PSD-95, thereby exhibiting physiological activation triggered via NMDA receptors. We have demonstrated previously that Ca2+/calmodulin-dependent protein kinase IIα (CaM-K IIα) directly phosphorylates nNOS at residue Ser847, and can attenuate the catalytic activity of the enzyme in neuronal cells [Komeima, Hayashi, Naito and Watanabe (2000) J. Biol. Chem. 275, 28139–28143]. In the present study, we examined how CaM-K II participates in the phosphorylation by analysing the functional interaction between nNOS and PSD-95 in cells. The results showed that PSD-95 directly promotes the nNOS phosphorylation at Ser847 induced by endogenous CaM-K II. In transfected cells, this effect of PSD-95 required its dual palmitoylation and the PDZ2 domain, but did not rely on its guanylate kinase domain. CaM-K Iα and CaM-K IV failed to phosphorylate nNOS at Ser847 in transfected cells. Thus PSD-95 mediates cellular trafficking of nNOS, and may be required for the efficient phosphorylation of nNOS at Ser847 by CaM-K II in neuronal cells.
Foetal cystic abdominal masses
Authors: McEwing Rachael , Hayward Christina , Furness Margaret
Published: June 2003

Foetal abdominal cysts are frequently found on routine antenatal ultrasound. Various sonographic features might help in their differential diagnosis. However, a definitive diagnosis is often not made until postnatal life, and detection of an intra‐abdominal cyst antenatally rarely alters obstetric management. A review of possible causes of a foetal abdominal cyst is presented.
Radiological manifestations of malignant pleural mesothelioma
Authors: Au Virginia WK , Thomas Meredith
Published: June 2003

Malignant pleural mesothelioma has had a rising incidence in Australia over the past 40 years. This pictorial essay gives a brief account of the condition, summarizes the various radiological manifestations and aims at increasing the awareness of a disease that is expected to reach its peak incidence in the early decades of the twenty‐first century.