bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antioxidants prevent UV‐induced apoptosis by inhibiting mitochondrial cytochrome c release and caspase activation in Spodoptera frugiperda (Sf9) cells
Authors: Mohan Manjari , Taneja Tarvinder K. , Sahdev Sudhir , Mohareer Krishnaveni , Begum Rasheedunnisa , Athar Mohammad , Sah Nand K. , Hasnain Seyed E. 
Published: June 2003

AbstractOxidative stress has been shown to be associated with apoptosis (programmed cell death) in a number of cell systems. We earlier reported in vitro cultured Spodoptera frugiperda (Sf9) cells as a model system to study oxidative stress induced apoptosis (J Biosciences 24 (1999) 13) and the inhibition of UV‐induced apoptosis by the baculovirus antiapoptotic p35 protein that acts as a sink to sequester reactive oxygen species (Proc Natl Acad Sci USA 96 (1999) 4838). We now show that UV‐induced apoptosis in Sf9 cells, is preceded by the release of mitochondrial cytochrome c into the cytosol and consequent activation of Sf‐caspase‐1. The inhibitory effect of different antioxidants including scavengers of oxygen radicals such as butylated hydroxyanisole (BHA), alpha tocopherol acetate, benzoate and reduced‐glutathione (GSH) on ultra violet B (UVB)‐induced apoptosis in cultured Sf9 cells was assessed. Both, cytochrome c release as well as Sf‐caspase‐1 activation was inhibited by pre‐treatment with antioxidants such as BHA and alpha tocopherol acetate, suggesting that these antioxidants inhibit apoptosis by acting quite upstream in the apoptosis cascade at the mitochondrial level, as well as downstream at the caspase level.
Dynamic changes in connexin expression correlate with key events in the wound healing process
Authors: Coutinho Petula , Qiu Cindy , Frank Stefanie , Tamber Kamaldeep , Becker David 
Published: June 2003

AbstractWound healing is a complex process requiring communication for the precise co‐ordination of different cell types. The role of extracellular communication through growth factors in the wound healing process has been extensively documented, but the role of direct intercellular communication via gap junctions has scarcely been investigated. We have examined the dynamics of gap junction protein (Connexins 26, 30, 31.1 and 43) expression in the murine epidermis and dermis during wound healing, and we show that connexin expression is extremely plastic between 6 hours and 12 days post‐wounding. The immediate response (6 h) to wounding is to downregulate all connexins in the epidermis, but thereafter the expression profile of each connexin changes dramatically. Here, we correlate the changing patterns of connexin expression with key events in the wound healing process.
Exportin 1‐independent nuclear export of GAPDH
Authors: Schmitz Hans‐Dirk , Dutiné Christine , Bereiter‐Hahn Jürgen 
Published: June 2003

AbstractGlyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) is a key enzyme of the glycolytic pathway. Recent studies have demonstrated an additional role in apoptosis: GAPDH is targeted to the nucleus during apoptotic signalling. This nuclear transport has also been observed in serum‐depleted cells, but it is reversible in fibroblasts, in contrast to apoptotic‐induced transport (Eur J Cell Biol 80 (2001) 419). Here, we analyse the serum depletion‐induced transport processes of GAPDH in NIH 3T3 cells. Prolonged serum depletion did not cause cell death, nuclear fragmentation (hoechst staining) or a significant increase in DNA strand‐breaks (comet assay). Using cells expressing green fluorescent protein (GFP)‐tagged GAPDH allowed us to monitor its intracellular localisation by confocal laser scanning microscopy (CLSM). Treatment of cells with the exportin1 inhibitor leptomycin B (LMB) did not influence cytoplasmic localisation of GFP—GAPDH, indicating that nuclear targeting of GAPDH is not constitutive and may be altered via a serum‐dependent regulatory export process. Suprisingly, the export of nuclear GFP—GAPDH after re‐addition of serum to starved cells was not prevented by LMB. Thus, nuclear export of GAPDH upon serum depletion is not mediated by exportin1.
Prognostic value of 6‐minute walk corridor test in patients with mild to moderate heart failure: comparison with other methods of functional evaluation
Authors: Rostagno Carlo , Olivo Giuseppe , Comeglio Marco , Boddi Vieri , Banchelli Michela , Galanti Giorgio , Gensini Gian Franco 
Published: June 2003

AbstractAim:The study was designed to evaluate the prognostic value of the 6‐min walk test (6MWT) in patients with mild to moderate congestive heart failure (CHF).Methods and results:Two hundred and fourteen patients (119 men and 95 women, mean age 64 years) were followed for a mean period of 34 months to assess event‐free survival (death, heart transplantation). Sixty‐six patients (34%) died (63 cardiovascular causes, 2 cancer and 1 stroke) and five patients underwent heart transplantation. For patients who walked <300 m during the 6MWT, survival was 62% compared with 82% in patients who walked 300–450 m or>450 m. With univariate analysis, NYHA class was the strongest predictor of death. LVEF (P<0.0001), aetiology of heart failure (P<0.001), LV filling pattern (P=0.002) and 6MWT distance (P<0.01) were all significantly related to survival. No significant relationship was found between survival, peak oxygen consumption or anaerobic threshold. Multivariate analysis using the Cox‐stepwise regression model showed that LV fractional shortening (P<0.009) and 6MWT distance (P<0.0005) were the strongest prognostic markers.Conclusion:A 6MWT distance of <300 m is a simple and useful prognostic marker of subsequent cardiac death in unselected patients with mild to moderate CHF.
Nondirectiveness and Its Lay Interpretations: The Effect of Counseling Style, Ethnicity and Culture on Attitudes Towards Genetic Counseling Among Jewish and Bedouin Respondents in Israel
Authors: Raz Aviad E. , Atar Marcela 
Published: June 2003

AbstractTo evaluate the effects of ethnicity, culture, and counseling style on the interpretation of nondirectiveness in genetic counseling, a questionnaire containing premarital and prenatal case vignettes in two versions (pessimistic/optimistic) was administered to 281 Jewish and 133 Bedouin respondents. The first study population was comprised of Jewish students enrolled in a university and a community college in the Negev (southern part of Israel). The second study population was comprised of Muslim‐Bedouin college students from the same area. The majority of Jewish respondents interpreted the nondirective message as intended by counselors, while the majority of Bedouin respondents did not. Counseling style was found to have a statistically significant effect on the interpretation of the general role of counseling. Gender and susceptibility were not found to have a significant effect on interpretation. Group differences are analyzed through a cultural lens in which different interpretive norms can generate expectations for either nondirectiveness or directiveness.
Subjective and Objective Risks of Carrying a BRCA1/2 Mutation in Individuals of Ashkenazi Jewish Descent
Authors: Kelly Kimberly , Leventhal Howard , Toppmeyer Deborah , Much Judy , Dermody James , Marvin Monica , Baran Jill , Schwalb Marvin 
Published: June 2003

AbstractThis repeated measures study examines (1) the change in subjective risk of mutations pre‐ to postcounseling, (2) the accuracy of BRCAPRO estimates of mutations, and (3) the discrepancy between subjective risk and BRCAPRO estimates of mutations before and after genetic counseling. Ninety‐nine Ashkenazi Jewish individuals pursued testing for BRCA1/2 mutations. Most had a personal cancer history (N = 51; family only: N = 48); and received uninformative negative results (N = 66; positives: N = 23; informative negative: N = 10). The coping strategy of defensive pessimism predicts that individuals will believe the worst case scenario to better cope with a potential negative outcome. Consistent with this, most felt they would have a mutation, if not mutations in both genes. The BRCAPRO model appeared to overestimate risk of having a mutation in this sample (p < .001). BRCAPRO overestimates notwithstanding, genetic counseling increased accuracy of subjective risk (p < .01). Individuals with a family‐only cancer history had the least accurate estimates of risk (p < .05) and may need further intervention to either manage anxiety or improve knowledge.
Oppression and Discrimination among Lesbian, Gay, Bisexual, and Transgendered People and Communities: A Challenge for Community Psychology
Authors: Harper Gary W. , Schneider Margaret 
Published: June 2003

AbstractLesbian, gay, bisexual, and transgendered (LGBT) people continue to experience various forms of oppression and discrimination in North America and throughout the world, despite the social, legal, and political advances that have been launched in an attempt to grant LGBT people basic human rights. Even though LGBT people and communities have been actively engaged in community organizing and social action efforts since the early twentieth century, research on LGBT issues has been, for the most part, conspicuously absent within the very field of psychology that is explicitly focused on community research and action–Community Psychology. The psychological and social impact of oppression, rejection, discrimination, harassment, and violence on LGBT people is reviewed, and recent advances in the areas of LGBT health, public policy, and research are detailed. Recent advances within the field of Community Psychology with regard to LGBT research and action are highlighted, and a call to action is offered to integrate the knowledge and skills within LGBT communities with Community Psychology's models of intervention, prevention, and social change in order to build better theory and intervention for LGBT people and communities.
Review Article: Chiari Type I Malformation with or Without Syringomyelia: Prevalence and Genetics
Authors: Speer Marcy C. , Enterline David S. , Mehltretter Lorraine , Hammock Preston , Joseph Judith , Dickerson Margaret , Ellenbogen Richard G. , Milhorat Thomas H. , Hauser Michael A. , George Timothy M. 
Published: June 2003

AbstractChiari type I malformation has traditionally been defined as a downward herniation of the cerebellar tonsils of ≥5 mm through the foramen magnum and it is likely associated with a volumetrically reduced posterior fossa. Syringomyelia is commonly associated with Chiari type I malformation. We estimate the prevalence of these two conditions and determine that they are more common than previously expected. We identify the genetic syndromes associated with some cases of Chiari type I malformation, and we provide evidence in favor of a genetic hypothesis for at least a subset of the nonsyndromic cases.
The Mpowerment Project: Community‐Building with Young Gay and Bisexual Men to Prevent HIV
Authors: Hays Robert B. , Rebchook Gregory M. , Kegeles Susan M. 
Published: June 2003

AbstractThe Mpowerment Project is a community‐level HIV prevention intervention for young gay and bisexual men ages 18–27. The program seeks to build a strong, supportive young gay and bisexual men's community where young gay and bisexual men nurture and protect each other, particularly with regard to HIV prevention. The program's theoretical framework draws from the areas of diffusion of innovations, community organizing, peer influence, and personal empowerment. The Mpowerment Project promotes a norm for safer sex through a variety of social, outreach and small group activities. The project is run by a “Core Group” of 12–15 young gay and bisexual men who, with volunteers, design and carry out all project activities. Implemented in 4 communities (Eugene, OR; Santa Barbara, CA; Albuquerque, NM; Austin, TX), the Mpowerment Project has proven to be effective in reducing high risk sex. This paper discusses the development and implementation of the program and various challenges encountered.
Science and Community Psychology: Social Norms for Pluralistic Inquiry
Authors: Kelly James G. 
Published: June 2003

AbstractThe 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.
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