bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers to Sun Safety in a Canadian Outpatient Population
Authors: Boggild Andrea K. , From Lynn 
Published: January 2004

Background: It has long been recognized that compliance with recommended sun safety practices is suboptimal, yet few investigations have explored the barriers that people face in practicing good sun safety. In this context, barriers can exist at the following three levels: Knowledge of sun safety, acquisition of sun safety information, and implementation of specific sun protective measures. Objective: The investigation reported herein sought to elucidate barriers to sun safety that individuals face. Ultimately, this study aimed to qualify the possible barriers that lead to a misalignment of current recommendations and sun safety practices. Methods: The study design was observational, and the instrument used for data collection was a self-administered questionnaire. Thirty-four outpatients of the RK Schachter Dermatology Centre of Sunnybrook and Women's College Health Sciences Centre (SWCHSC), Toronto, Ontario, as well as 27 outpatients of the Sport Care facility of SWCHSC were enrolled in the study. They represent the target population of those who are at greater risk of developing sun-related skin lesions. Data were analyzed using standard parametric and nonparametric techniques. Comparisons were made between the two outpatient groups and between other groups within the sample. Results: In general, level of sun safety knowledge was fairly high, though compliance to sun safety measures was suboptimal in both populations. There were no significant differences regarding level of knowledge between the 2 outpatient groups. Deficiencies in knowledge centered around risk factors for skin cancer. Frequently cited barriers to sun safety include inconvenience (34% of respondents), forgetting to use sun safety measures (49%), a desire to be tanned (33%), and protective clothing being too hot to wear (56%). High compliers were notable for their great likelihood of being counseled by a physician about sun safety ( P < 0.025) and their slightly higher mean knowledge scores. Conclusions: These data support that knowledge alone does not predict compliance and that sun awareness campaigns should be evaluated based on their ability to affect behavior.
‘Over to you’: Can Europe restrain Microsoft's threat to freedom of musical expression in computer-mediated communication?
Authors: WOLFE ARNOLD S. 
Published: January 2004

The United States Supreme Court characterised the trend toward the convergence of the communication, music and computer worlds as ‘a promising new medium that could empower citizens and promote democracy in the next millennium’. Yet inquiry into United States vs Microsoft, the case that may determine whether ‘the free and open nature of … computer-assisted communication’ will remain ‘free and open’ has been lacking. This study focuses on the antitrust and First Amendment implications of Microsoft's disputed strategy of marrying its Web browser to its operating system (OS) software.The study argues that rulings on the legality of this strategy have
ramifications for Microsoft's subsequent move to suture its streaming audio and video software to its OS product. Implications of this case – and the European Commission's similar inquiry into such suturing – for popular music as an industry, as an industrialised technology, and as a form of communication are discussed. Scholars, practitioners, and fans must be ever mindful that when one firm dominates a human enterprise as central to contemporary life as personal computing, the opportunity for abuse exists.
Patterns of changes in temperament and character inventory scales in subjects with obsessive–compulsive disorder following a 4‐month treatment
Authors: Lyoo I. K. , Yoon T. , Kang D. H. , Kwon J. S. 
Published: January 2004

Objective:  The purpose of this study was to assess changes in the temperament and character patterns in subjects with obsessive–compulsive disorder (OCD) following the treatment for obsessive/compulsive and accompanying depressive symptoms.Method:  Study subjects were 35 patients who met the DSM‐IV criteria for OCD. All subjects were assessed with the Temperament and Character Inventory (TCI), the Yale‐Brown Obsessive–Compulsive Scale, the Beck Depression Inventory, and the Beck Anxiety Inventory before and after a 4‐month treatment.Results:  Harm Avoidance (HA) scores in OCD subjects before treatment significantly decreased after treatment. However, the Self‐Directedness scores, which were significantly lower than healthy comparison subjects before treatment, did not change. In addition, Reward Dependence scores in OCD subjects, which were not significantly different from healthy comparison subjects before treatment, significantly increased after treatment.Conclusion:  The TCI pattern of untreated OCD subjects (high HA and low Self‐Directedness, relative to healthy comparison subjects) and the decrease of HA scores and no change in Self‐Directedness scores following a successful treatment suggest that temperaments are more amenable to treatment than characters.
Anterior cingulotomy for refractory obsessive–compulsive disorder
Authors: Kim C.‐H. , Chang J. W. , Koo M.‐S. , Kim J. W. , Suh H. S. , Park I. H. , Lee H. S. 
Published: January 2004

Objective: This study was designed to prospectively investigate the efficacy and cognitive adverse effects of stereotactic bilateral anterior cingulotomy as a treatment for refractory obsessive–compulsive (OCD) patients for 12 months.Method: Patients were eligible if they had severe OCD and rigorous treatments had been unsuccessful. Yale‐Brown Obsessive–Compulsive Scale (Y‐BOCS), Clinical Global Impression (CGI) and neuropsychological tests were used to assess the efficacy and cognitive changes of cingulotomy before and 12 months after operation.Results: The mean improvement rate of the Y‐BOCS scores achieved from baseline was 36.0%. Out of 14 patients six met responder criteria; 35% or higher improvement rate on Y‐BOCS and CGI improvement of very much or much better at 12‐month follow‐up. There was no significant cognitive dysfunction after cingulotomy.Conclusion: Anterior cingulotomy shows few cognitive adverse effects, with about half of the OCD patients demonstrating significant symptomatic improvement.
Does prophylaxis‐delay in bipolar disorder influence outcome? Results from a long‐term study of 147 patients
Authors: Baethge C. , Smolka M. N. , Gruschka P. , Berghöfer A. , Schlattmann P. , Bauer M. , Altshuler L. , Grof P. , Müller‐Oerlinghausen B. 
Published: January 2004

Objective: This study investigated the impact of latency (the time between illness onset and initiation of prophylactic treatment) on the outcome of prophylaxis in bipolar disorders.Method: The effect of prophylaxis delay (latency) on the course of illness was assessed in 147 patients. Dependent variables were: reduction of days spent in the hospital (prior to vs. during prophylaxis), time to first recurrence, and Morbidity‐Index during prophylaxis (lithium or carbamazepine). Latency and other independent variables were tested using a multivariate approach.Results: Latency (9.3 years on average) had no significant effect on the subsequent response. Illness severity prior to prophylaxis, however, did predict the relative response. The course of illnessduringtreatment could not be predicted by any one factor.Conclusion: The delay in initiating prophylaxis appears to have no influence on prophylaxis outcome. Instead, those whose illness was more severe were treated earlier and these patients subsequently showed a relatively greater response. If severity is not controlled for as part of the analysis, latency may be mistaken as an important predictor for response.
Children of parents with obsessive‐compulsive disorder – a 2‐year follow‐up study
Authors: Black D. W. , Gaffney G. R. , Schlosser S. , Gabel J. 
Published: January 2004

Objective:  To examine the association between parental obsessive‐compulsive disorder (OCD) and emotional and behavioural disorders in offspring.Method:  Demographic, clinical, and diagnostic data were collected from parents with OCD, control subjects, and their respective offspring. Offspring were reassessed at a 2‐year follow‐up.Results:  Probands with OCD and controls were relatively well matched for age, gender, race, educational rating, and marital status. Offspring of OCD probands were at greater risk than offspring of controls for dimensionally measured anxiety, depression, somatization, and social problems. OCD offspring were significantly more likely than control offspring to have lifetime overanxious disorder, separation anxiety disorder, OCD, or ‘any anxiety disorder’. Female gender in the parent with OCD, evidence of family dysfunction, and high symptom levels in offspring were predictive of broadly defined OCD at follow‐up.Conclusion:  Children having a parent with OCD are more likely than control offspring to have social, emotional, and behavioural disorders.
Affective (depressive) morbidity in puerperal Nigerian women: validation of the Edinburgh postnatal depression scale
Authors: Uwakwe Richard 
Published: January 2004

Objective:  To determine the rate of depression in a group of postpartum Nigerian women and to validate the Edinburgh Postnatal Depression Scale (EPDS) in this group.Method:  Between April and August 2000, all postpartum women who remained in the maternity ward for up to 7 days, and those who attended the postnatal clinics of Nnamdi Azikiwe University Teaching Hospital were recruited. Translated local language versions of the EPDS and the Zung Self‐Rating Depression Scale were used to screen the subjects. A structured interview schedule was adapted from the depression section of the Composite International Diagnostic Interview and affective module of the ICD‐10 Symptom Check List to assess screened subjects.Results:  The total rejection rate was 23%, with 225 women participating in the study. Twenty‐four subjects (10.7%) had depression. At the optimal cut‐off score of 9, the EPDS had a sensitivity of 0.75, and specificity of 0.97.Conclusion:  The EPDS clearly distinguished between depressed and non‐depressed postpartum mothers (t = 7.63, P < 0.001, df = 222). Because of its brevity and acceptability, it is recommended that the EPDS be used in routine postnatal screening.
Protein kinase C modulation of the regulation of sarcoplasmic reticular function by protein kinase A‐mediated phospholamban phosphorylation in diabetic rats
Authors: Watanuki Satoko , Matsuda Naoyuki , Sakuraya Fumika , Jesmin Subrina , Hattori Yuichi 
Published: January 2004

The goal of this study was to elucidate the possible mechanisms by which protein kinase A (PKA)‐mediated regulation of the sarcoplasmic reticulum (SR) via phospholambin protein phosphorylation is functionally impaired in streptozotocin‐induced diabetic rats.
Phospholamban (PLB) protein and mRNA levels were 1.3‐fold higher in diabetic than in control hearts, while protein expression of cardiac SR Ca2+‐ATPase (SERCA2a) was unchanged.
Basal and isoprenaline‐stimulated phosphorylation of PLB at Ser16 or Thr17 was unchanged in diabetic hearts. However, stronger immunoreactivity was observed at the basal level in diabetic hearts when antiphosphoserine antibody was used.
Basal 32P incorporation into PLB was significantly higher in diabetic than in control SR vesicles, but the extent of the PKA‐mediated increase in PLB phosphorylation was the same in the two groups of vesicles.
Stimulation of Ca2+ uptake by PKA‐catalyzed PLB phosphorylation was weaker in diabetic than in control SR vesicles. The PKA‐induced increase in Ca2+ uptake was attenuated when control SR vesicles were preincubated with protein kinase C (PKC).
PKC activities were increased by more than two‐fold in the membranous fractions from diabetic hearts in comparison with control values, regardless of whether Ca2+ was present. This was associated with increases in the protein content of PKCδ, PKCη, PKCι, and PKCλ in diabetic membranous fractions.
The changes observed in diabetic rats were reversed by insulin therapy.
These results suggest that PKA‐dependent phosphorylation may incompletely counteract the function of PLB as an inhibitor of SERCA2a activity in diabetes in which PKC expression and activity are enhanced.

British Journal of Pharmacology (2004) 141, 347–359. doi:10.1038/sj.bjp.0705455
Endosome sorting of β2‐adrenoceptors is GRK5 independent
Authors: Millman Ellen E , Rosenfeld Jennifer L , Vaughan David J , Nguyen Jacqueline , Dai WenPing , Alpizar‐Foster Estrella , Clark Richard B , Knoll Brian J , Moore Robert H 
Published: January 2004

We have investigated the role of G protein‐coupled receptor kinase 5 (GRK5) in the regulation of endosome sorting of human β2‐adrenoceptors.
Expressing GRK5 at a high level significantly increased the extent of internalization of wild‐type β2‐adrenoceptors and of an internalization‐defective mutant receptor, and increased receptor phosphorylation at serines 355 and 356 in the cytoplasmic tail.
Overexpressing GRK5 did not alter β2‐adrenoceptor recycling as assessed by immunofluorescence microscopy and radioligand binding assays nor was there any change in receptor downregulation.
These data indicate that GRK5 does not regulate the sorting of β2‐adrenoceptors in the endocytic pathway.

British Journal of Pharmacology (2004) 141, 277–284. doi:10.1038/sj.bjp.0705504
A1 and A2A adenosine receptor modulation of α1‐adrenoceptor‐mediated contractility in human cultured prostatic stromal cells
Authors: Preston A , Frydenberg M , Haynes J M 
Published: January 2004

This study investigated the possibility that adenosine receptors modulate the α1‐adrenoceptor‐mediated contractility of human cultured prostatic stromal cells (HCPSC).
The nonselective adenosine receptor agonist, 5′‐N‐ethylcarboxamido‐adenosine (NECA; 10 nM–10 μM), and the A1 adenosine receptor selective agonist, cyclopentyladenosine (CPA; 10 nM–10 μM), elicited significant contractions in HCPSC, with maximum contractile responses of 18±3% and 17±2% reduction in initial cell length, respectively.
In the presence of a threshold concentration of phenylephrine (PE) (100 nM), CPA (1 nM–10 μM) caused contractions, with an EC50 of 124±12 nM and maximum contractile response of 37±4%. The A1 adenosine receptor‐selective antagonist 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX 100 nM) blocked this effect. In the presence of DPCPX (100 nM), NECA (1 nM–10 μM) inhibited contractions elicited by a submaximal concentration of PE (10 μM), with an IC50 of 48±2 nM. The A2A adenosine receptor‐selective antagonist 4‐(2‐[7‐amino‐2‐{furyl}{1,2,4}triazolo{2,3‐α}{1,3,5,}triazin‐5‐yl amino]ethyl)phenol (Zm241385 100 nM) blocked this effect.
In BCECF‐AM (10 μM)‐loaded cells, both CPA (100 pM–1 μM) and NECA (100 pM–10 μM) elicited concentration‐dependent decreases in intracellular pH (pHi), with EC50 values of 3.1±0.3 and 6.0±0.3 nM, respectively. The response to NECA was blocked by Zm241385 (100 nM; apparent pKB of 9.4±0.4), but not by DPCPX (100 nM). The maximum response to CPA was blocked by DPCPX (100 nM), and unaffected by Zm241385 (100 nM).
NECA (10 nM–10 μM) alone did not increase [3H]‐cAMP in HCPSC. In the presence of DPCPX (100 nM), NECA (10 nM–10 μM) caused a concentration dependent increase in [3H]‐cAMP, with an EC50 of 1.2±0.1 μM. This response was inhibited by Zm241385 (100 nM). CPA (10 nM–10 μM) had no effect on cAMP, in the presence or absence of forskolin (1 μM).
These findings are consistent with a role for adenosine receptors in the modulation of adrenoceptor‐mediated contractility in human prostate‐derived cells.

British Journal of Pharmacology (2004) 141, 302–310. doi:10.1038/sj.bjp.0705535
Coupling of boswellic acid‐induced Ca2+ mobilisation and MAPK activation to lipid metabolism and peroxide formation in human leucocytes
Authors: Altmann Anja , Poeckel Daniel , Fischer Lutz , Schubert‐Zsilavecz Manfred , Steinhilber Dieter , Werz Oliver 
Published: January 2004

We have previously shown that 11‐keto boswellic acids (11‐keto‐BAs), the active principles of Boswellia serrata gum resins, activate p38 MAPK and p42/44MAPK and stimulate Ca2+ mobilisation in human polymorphonuclear leucocytes (PMNL).
In this study, we attempted to connect the activation of MAPK and mobilisation of Ca2+ to functional responses of PMNL, including the formation of reactive oxygen species (ROS), release of arachidonic acid (AA), and leukotriene (LT) biosynthesis.
We found that, in PMNL, 11‐keto‐BAs stimulate the formation of ROS and cause release of AA as well as its transformation to LTs via 5‐lipoxygenase.
Based on inhibitor studies, 11‐keto‐BA‐induced ROS formation is Ca2+‐dependent and is mediated by NADPH oxidase involving PI 3‐K and p42/44MAPK signalling pathways. Also, the release of AA depends on Ca2+ and p42/44MAPK, whereas the pathways stimulating 5‐LO are not readily apparent.
Pertussis toxin, which inactivates Gi/0 protein subunits, prevents MAPK activation and Ca2+ mobilisation induced by 11‐keto‐BAs, implying the involvement of a Gi/0 protein in BA signalling.
Expanding studies on differentiated haematopoietic cell lines (HL60, Mono Mac 6, BL41‐E‐95‐A) demonstrate that the ability of BAs to activate MAPK and to mobilise Ca2+ may depend on the cell type or the differentiation status.
In summary, we conclude that BAs act via Gi/0 protein(s) stimulating signalling pathways that control functional leucocyte responses, in a similar way as chemoattractants, that is, N‐formyl‐methionyl‐leucyl‐phenylalanine or platelet‐activating factor.

British Journal of Pharmacology (2004) 141, 223–232. doi:10.1038/sj.bjp.0705604
Antitussive activity of sigma‐1 receptor agonists in the guinea‐pig
Authors: Brown Claire , Fezoui Malika , Selig William M , Schwartz Carl E , Ellis James L 
Published: January 2004

Current antitussive medications have limited efficacy and often contain the opiate‐like agent dextromethorphan (DEX). The mechanism whereby DEX inhibits cough is ill defined. DEX displays affinity at both NMDA and sigma receptors, suggesting that the antitussive activity may involve central or peripheral activity at either of these receptors. This study examined and compared the antitussive activity of DEX and various putative sigma receptor agonists in the guinea‐pig citric‐acid cough model.
Intraperitoneal (i.p.) administration of DEX (30 mg kg−1) and the sigma‐1 agonists SKF‐10,047 (1–5 mg kg−1), Pre‐084 (5 mg kg−1), and carbetapentane (1–5 mg kg−1) inhibited citric‐acid‐induced cough in guinea‐pigs. Intraperitoneal administration of a sigma‐1 antagonist, BD 1047 (1–5 mg kg−1), reversed the inhibition of cough elicited by SKF‐10,047. In addition, two structurally dissimilar sigma agonists SKF‐10,047 (1 mg ml−1) and Pre‐084 (1 mg ml−1) inhibited cough when administered by aerosol.
Aerosolized BD 1047 (1 mg ml−1, 30 min) prevented the antitussive action of SKF‐10,047 (5 mg kg−1) or DEX (30 mg kg−1) given by i.p. administration and, likewise, i.p. administration of BD 1047 (5 mg kg−1) prevented the antitussive action of SKF‐10,047 given by aerosol (1 mg ml−1).
These results therefore support the argument that antitussive effects of DEX may be mediated via sigma receptors, since both systemic and aerosol administration of sigma‐1 receptor agonists inhibit citric‐acid‐induced cough in guinea‐pigs. While significant systemic exposure is possible with aerosol administration, the very low doses administered (estimated <0.3 mg kg−1) suggest that there may be a peripheral component to the antitussive effect.

British Journal of Pharmacology (2004) 141, 233–240. doi:10.1038/sj.bjp.0705605
Membrane type‐1 matrix metalloproteinase stimulates tumour cell‐induced platelet aggregation: role of receptor glycoproteins
Authors: Alonso‐Escolano David , Strongin Alex Y , Chung Ada W , Deryugina Elena I , Radomski Marek W 
Published: January 2004

Matrix metalloproteinase‐2 (MMP‐2) plays a role in agonist‐ and tumour cell‐induced platelet aggregation (TCIPA).
MMP‐2 is synthesized as a proenzyme and is activated at the cell surface by membrane type‐1 matrix metalloproteinase (MT1‐MMP, MMP‐14).
The significance of tumour cell‐associated MT1‐MMP for TCIPA was investigated using human breast carcinoma MCF7 cells stably coexpressing the integrin αvβ3 with MT1‐MMP, cells expressing αvβ3 alone and mock‐transfected cells.
Western blot and zymography confirmed that αvβ3/MT1‐MMP cells expressed MT1‐MMP and efficiently processed proMMP‐2 to MMP‐2.
Aggregometry, phase‐contrast and transmission electron microscopy and flow cytometry were used to characterize TCIPA induced by MCF7 cell lines.
The aggregating potency of cells was: αvβ3/MT1‐MMP >αvβ3=mock cells, as shown by aggregometry and phase‐contrast microscopy.
Electron microscopy revealed close, membrane–membrane interactions between activated platelets and αvβ3/MT1‐MMP cells during TCIPA.
Inhibition of MMP‐2 with the neutralizing anti‐MMP‐2 antibody (5 μg ml−1) and o‐phenanthroline (100 μM) reduced aggregation induced by αvβ3/MT1‐MMP cells.
TCIPA induced by αvβ3/MT1‐MMP cells was also reduced by inhibiting the generation and actions of ADP with apyrase (250 μg ml−1) and 2‐methylthio‐AMP (2‐MeSAMP) (30 μM), but not N6‐methyl‐2′‐deoxyadenosine‐3′,5′‐bisphosphate (MRS2179) (30 μM).
Flow cytometry demonstrated that TCIPA enhanced expression of glycoprotein (GP) Ib and IIb/IIIa receptors not only on platelets but also on breast cancer cells.
Thus, (a) human breast carcinoma cell surface‐associated MT1‐MMP, via activating proMMP‐2, stimulates TCIPA; (b) ADP amplifies the effects of MMPs via stimulation of P2Y12 receptors and (c) both tumour‐ and platelet‐derived GPIb and GPIIb/IIIa are involved in the aggregatory effects of MT1‐MMP.

British Journal of Pharmacology (2004) 141, 241–252. doi:10.1038/sj.bjp.0705606
Calcineurin‐independent inhibition of mitochondrial Ca2+ uptake by cyclosporin A
Authors: Montero M , Lobatón C D , Gutierrez‐Fernández S , Moreno A , Alvarez J 
Published: January 2004

Cyclosporin A (CsA) is a widely used compound because of its potent immunosupressive properties, derived mainly from the inhibition of calcineurin, and also because of its ability to block the mitochondrial permeability transition pore (PTP). This second effect has been involved in the protection against apoptosis mediated by release of mitochondrial factors. We show here that CsA (1–10μM) has an additional effect on Ca2+ homeostasis in mitochondria that cannot be attributed to inhibition of PTP.
By measuring specifically mitochondrial [Ca2+] with targeted aequorin, we show that CsA inhibited Ca2+ entry into mitochondria both in intact and in permeabilized cells, and this effect was stronger when Ca2+ entry was triggered by low cytosolic [Ca2+], below 5 μM.
Inhibition of mitochondrial Ca2+ uptake required micromolar concentrations of CsA and was not mimicked by other inhibitors of calcineurin such as FK‐506 or cypermethrin, nor by a different inhibitor of the PTP, bongkrekic acid.
CsA blocked the increase in mitochondrial Ca2+ uptake rate induced by the mitochondrial Ca2+ uniporter activator SB202190.
Our results suggest that CsA inhibits Ca2+ entry through the Ca2+ uniporter by a mechanism independent of the inhibition of PTP or calcineurin. This effect may contribute to reduce depolarization and Ca2+ overloading in mitochondria after cell stimulation, and thus cooperate with the direct inhibition of PTP to prevent apoptosis.

British Journal of Pharmacology (2004) 141, 263–268. doi:10.1038/sj.bjp.0705609