bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alkylation of prohibitin by cyclohexylphenyl‐chloroethyl urea on an aspartyl residue is associated with cell cycle G1 arrest in B16 cells
Authors: Bouchon B , Papon J , Communal Y , Madelmont J‐C , Degoul F 
Published: August 2007

Background and purpose:Phenyl‐chloroethyl ureas (CEUs) are a class of anticancer drugs that mainly react with proteins. Two molecules of this family, cyclohexylphenyl‐chloroethyl urea (CCEU) and iodophenyl‐chloroethyl urea (ICEU) induced G1/S and G2/M cell cycle blocks, respectively. We hypothesised that these observations were linked to a differential protein alkylation pattern.Experimental approach:Proteins from B16 cells incubated with [14C‐urea]‐CCEU and [125I]‐ICEU were compared by 2D‐analyses followed by MALDI‐TOF identification of modified proteins and characterisation of the CCEU binding. Protein expression was investigated by Western blot analyses and cell cycle data were obtained by flow cytometry.Key results:Several proteins (PDIA1, PDIA3, PDIA6, TRX, VDAC2) were alkylated by both ICEU and CCEU but β‐tubulin and prohibitin (PHB) were specifically alkylated by either ICEU or CCEU respectively. Specific alkylation of these two proteins might explain the observed difference in B16 cell cycle arrest in G2 and G1 phases respectively. Mass spectrometry studies on the alkylated prohibitin localised the modified peptide and identified Asp‐40 as the target for CCEU. This alkylation induced an increased cellular content of PHB that should contribute to the accumulation of cells in G1 phase.Conclusions and implications:This study reinforces our findings that CEUs alkylate proteins through an ester linkage with an acidic amino acid and shows that PHB alkylation contributes to G1/S arrest in CCEU treated B16 cells. Modification of PHB status and/or activity is an open route for new cancer therapeutics.British Journal of Pharmacology (2007) 152, 449–455; doi:10.1038/sj.bjp.0707415; published online 20 August 2007
The molecular mechanism of the inhibition by licofelone of the biosynthesis of 5‐lipoxygenase products
Authors: Fischer L , Hornig M , Pergola C , Meindl N , Franke L , Tanrikulu Y , Dodt G , Schneider G , Steinhilber D , Werz O 
Published: August 2007

Background and purpose:Licofelone is a dual inhibitor of the cyclooxygenase and 5‐lipoxygenase (5‐LO) pathway, and has been developed for the treatment of inflammatory diseases. Here, we investigated the molecular mechanisms underlying the inhibition by licofelone of the formation of 5‐LO products.Experimental approach:The efficacy of licofelone to inhibit the formation of 5‐LO products was analysed in human isolated polymorphonuclear leukocytes (PMNL) or transfected HeLa cells, as well as in cell‐free assays using respective cell homogenates or purified recombinant 5‐LO. Moreover, the effects of licofelone on the subcellular redistribution of 5‐LO were studied.Key results:Licofelone potently blocked synthesis of 5‐LO products in Ca2+‐ionophore‐activated PMNL (IC50=1.7 μM) but was a weak inhibitor of 5‐LO activity in cell‐free assays (IC50≫10 μ
M). The structures of licofelone and MK‐886, an inhibitor of the 5‐LO‐activating protein (FLAP), were superimposable. The potencies of both licofelone and MK‐886 in ionophore‐activated PMNL were impaired upon increasing the concentration of arachidonic acid, or under conditions where 5‐LO product formation was evoked by genotoxic, oxidative or hyperosmotic stress. Furthermore, licofelone prevented nuclear redistribution of 5‐LO in ionophore‐activated PMNL, as had been observed for FLAP inhibitors. Finally, licofelone as well as MK‐886 caused only moderate inhibition of the synthesis of 5‐LO products in HeLa cells, unless FLAP was co‐transfected.Conclusions and implications:Our data suggest that the potent inhibition of the biosynthesis of 5‐LO products by licofelone requires an intact cellular environment and appears to be due to interference with FLAP.British Journal of Pharmacology (2007) 152, 471–480; doi:10.1038/sj.bjp.0707416; published online 20 August 2007
Endocannabinoids and the haematological system
Authors: Randall M D 
Published: August 2007

Endocannabinoids are blood borne and may also be secreted by the endothelium. Accordingly, there has been interest in the interactions between (endo)cannabinoids and blood cells. There is certainly evidence that (endo)cannabinoids may promote platelet activation, indicating that they may be thrombogenic. Platelets are involved both in the metabolism and release of endocannabinoids, and so it is possible that their circulating levels may be regulated by platelets. This process is altered in disease states such that platelet‐derived endocannabinoids contribute towards hypotension in cardiovascular shock. Not only may endocannabinoids regulate platelet function and possibly lead to thrombogenesis, but they may also influence haematopoiesis. Given these emerging roles, the aim of this review is to examine the interactions between cannabinoids and blood.British Journal of Pharmacology (2007) 152, 671–675; doi:10.1038/sj.bjp.0707420; published online 20 August 2007
Role and regulation of acylethanolamides in energy balance: focus on adipocytes and β‐cells
Authors: Matias I , Gonthier M‐P , Petrosino S , Docimo L , Capasso R , Hoareau L , Monteleone P , Roche R , Izzo A A , Di Marzo V 
Published: August 2007

The endocannabinoid, arachidonoylethanolamide (AEA), and the peroxisome proliferator‐activated receptor (PPAR)‐α ligand, oleylethanolamide (OEA) produce opposite effects on lipogenesis. The regulation of OEA and its anti‐inflammatory congener, palmitoylethanolamide (PEA), in adipocytes and pancreatic β‐cells has not been investigated. We report here the results of studies on acylethanolamide regulation in these cells during obesity and hyperglycaemia, and provide an overview of acylethanolamide role in metabolic control. We analysed by liquid chromatography‐mass spectrometry OEA and PEA levels in: 1) mouse 3T3F442A adipocytes during insulin‐induced differentiation, 2) rat insulinoma RIN m5F β‐cells kept in ‘low’ or ‘high’ glucose, 3) adipose tissue and pancreas of mice with high fat diet‐induced obesity (DIO), and 4) in visceral fat or blood of obese or type 2 diabetes (T2D) patients. In adipocytes, OEA levels remain unchanged during differentiation, whereas those of PEA decrease significantly, and are under the negative control of both leptin and PPAR‐γ. PEA is significantly downregulated in subcutaneous adipose tissue of DIO mice. In RIN m5F insulinoma β‐cells, OEA and PEA levels are inhibited by ‘very high’ glucose, this effect being enhanced by insulin, whereas in cells kept for 24 h in ‘high’ glucose, they are stimulated by both glucose and insulin. Elevated OEA and PEA levels are found in the blood of T2D patients. Reduced PEA levels in hypertrophic adipocytes might play a role in obesity‐related pro‐inflammatory states. In β‐cells and human blood, OEA and PEA are down‐ or up‐regulated under conditions of transient or chronic hyperglycaemia, respectively.British Journal of Pharmacology (2007) 152, 676–690; doi:10.1038/sj.bjp.0707424; published online 20 August 2007
Roflumilast inhibits leukocyte‐endothelial cell interactions, expression of adhesion molecules and microvascular permeability
Authors: Sanz M‐J , Cortijo J , Taha M A , Cerdá‐Nicolás M , Schatton E , Burgbacher B , Klar J , Tenor H , Schudt C , Issekutz A C , Hatzelmann A , Morcillo E J 
Published: August 2007

Background and purpose:The present study addressed the effects of the investigational PDE4 inhibitor roflumilast on leukocyte‐endothelial cell interactions and endothelial permeabilityin vivoandin vitro.Experimental approach:In vivo, intravital video‐microscopy was used to determine effects of roflumilast p.o. on leukocyte‐endothelial cell interactions and microvascular permeability in rat mesenteric venules.In vitro, the effects of roflumilast N‐oxide, the active metabolite of roflumilast in humans, and other PDE4 inhibitors on neutrophil adhesion to tumour necrosis factorα(TNFα)‐activated human umbilical vein endothelial cells (HUVEC), E‐selectin expression and thrombin‐induced endothelial permeability was evaluated. Flow cytometry was used to determine the effect of roflumilast onN‐formyl‐methionyl‐leucyl‐phenylalanine (fMLP)‐induced CD11b upregulation on human neutrophils.Key results:In vivo, roflumilast, given 1 h before lipopolysaccharide (LPS), dose‐dependently reduced leukocyte‐endothelial cell interactions in rat mesenteric postcapillary venules. It also diminished histamine‐induced microvascular permeability. Immunohistochemical analyses revealed that roflumilast prevented LPS‐induced endothelial P‐ and E‐selectin expression.In vitro, roflumilast N‐oxide concentration‐dependently suppressed neutrophil adhesion to TNFα‐activated HUVEC and CD11b expression on fMLP‐stimulated neutrophils. It also reduced TNFα‐induced E‐selectin expression on HUVEC, when PDE3 activity was blocked. HUVEC permeability elicited by thrombin was concentration‐dependently suppressed by roflumilast N‐oxide. While roflumilast N‐oxide was as potent as roflumilast at inhibiting stimulated endothelial cell and neutrophil functions, both compounds were significantly more potent than the structurally unrelated PDE4 inhibitors, rolipram or cilomilast.Conclusions and implications:These findings further support earlier observations on the inhibition of inflammatory cell influx and protein extravasation by roflumilastin vivo.British Journal of Pharmacology(2007)152, 481–492; doi:10.1038/sj.bjp.0707428; published online 20 August 2007
Characterization of 4‐(2‐hydroxyphenyl)‐1‐[2′‐[N‐(2″‐pyridinyl)‐p‐fluorobenzamido]ethyl]piperazine (p‐DMPPF) as a new potent 5‐HT1Aantagonist
Authors: Defraiteur C , Plenevaux A , Scuvée‐Moreau J , Rouchet N , Goblet D , Luxen A , Seutin V 
Published: August 2007

Background and purpose:The identification of potent and selective radioligands for the mapping of 5‐HT receptors is interesting both for clinical and experimental research. The aim of this study was to compare the potency of a new putative 5‐HT1Areceptor antagonist,p‐DMPPF, (4‐(2‐hydroxyphenyl)‐1‐[2′‐[N‐(2′′‐pyridinyl)‐p‐fluorobenzamido]ethyl]piperazine) with that of the well‐known 5‐HT1Aantagonists, WAY‐100635 (N‐[2‐[4‐(2‐methoxyphenyl)‐1‐piperazinyl]‐ethyl]‐N‐(2‐pyridinyl) cyclohexanecarboxamide) and its fluorobenzoyl analogue,p‐MPPF (4‐(2‐methoxyphenyl)‐1‐[2′‐[N‐(2″‐pyridinyl)‐p‐fluorobenzamido]ethyl]piperazine).Experimental approach:Single cell extracellular recordings of dorsal raphe (DR) neurones were performed in rat brain slices. The potency of each compound at antagonizing the effect of the 5‐HT1Aagonist, 8‐OH‐DPAT [8‐hydroxy‐2‐(di‐n‐propylamino)‐tetraline], was quantified using the Schild equation. The pharmacological profile ofp‐DMPPF was defined using competition binding assays.Key results:Consistently with a 5‐HT1Areceptor antagonist profile, incubation of slices with an equimolar (10 nM) concentration of each compound markedly reduced the inhibitory effect of 8‐OH‐DPAT on the firing rate of DR neurones, causing a significant rightward shift in its concentration‐response curve. The rank order of potency of the antagonists was WAY‐100635>p‐DMPPFp‐MPPF. The sensitivity of DR neurones to the inhibitory effect of 8‐OH‐DPAT was found to be heterogeneous. The binding experiments demonstrated thatp‐DMPPF is highly selective for 5‐HT1Areceptors, with aKivalue of 7 nM on these receptors.Conclusions and implications:The potency of the new compound,p‐DMPPF, as a 5‐HT1Aantagonist is similar to that ofp‐MPPF in our electrophysiological assay. Its selectivity towards 5‐HT1Areceptors makes it a good candidate for clinical development.British Journal of Pharmacology(2007)152, 952–958; doi:10.1038/sj.bjp.0707431; published online 20 August 2007
Novel approaches to developing new antibiotics for bacterial infections
Authors: Coates A R M , Hu Y 
Published: August 2007

Antibiotics are an essential part of modern medicine. The emergence of antibiotic‐resistant mutants among bacteria is seemingly inevitable, and results, within a few decades, in decreased efficacy and withdrawal of the antibiotic from widespread usage. The traditional answer to this problem has been to introduce new antibiotics that kill the resistant mutants. Unfortunately, after more than 50 years of success, the pharmaceutical industry is now producing too few antibiotics, particularly against Gram‐negative organisms, to replace antibiotics that are no longer effective for many types of infection. This paper reviews possible new ways to discover novel antibiotics. The genomics route has proven to be target rich, but has not led to the introduction of a marketed antibiotic as yet. Non‐culturable bacteria may be an alternative source of new antibiotics. Bacteriophages have been shown to be antibacterial in animals, and may find use in specific infectious diseases. Developing new antibiotics that target non‐multiplying bacteria is another approach that may lead to drugs that reduce the emergence of antibiotic resistance and increase patient compliance by shortening the duration of antibiotic therapy. These new discovery routes have given rise to compounds that are in preclinical development, but, with one exception, have not yet entered clinical trials. For the time being, the majority of new antibiotics that reach the marketplace are likely to be structural analogues of existing families of antibiotics or new compounds, both natural and non‐natural which are screened in a conventional way against live multiplying bacteria.British Journal of Pharmacology(2007)152, 1147–1154; doi:10.1038/sj.bjp.0707432; published online 20 August 2007
Isolation and assessment of phytate‐hydrolysing bacteria from the DelMarVa Peninsula
Authors: Hill Jane E. , Kysela David , Elimelech Menachem 
Published: August 2007

SummaryThe Delaware–Maryland–Virginia (DelMarVa) Peninsula, flanking one side of the Chesapeake Bay, is home to a substantial broiler chicken industry. As such, it produces a significant amount of manure that is typically composted and spread onto local croplands as a fertilizer. Phytate (myo inositol hexakisphosphate), the major form of organic phosphorus in the manure, can be hydrolysed by microorganisms to produce orthophosphate. Orthophosphate is a eutrophication agent which can lead to algal blooms, hypoxia and fish kills in the Chesapeake Bay and its tributaries. This transect study reveals a subpopulation of heterotrophic, thiosulfate‐utilizing bacteria that can degrade phytate within the watershed as well as its receiving water sediment. Aerobic isolates were typical soil bacteria, e.g. Pseudomonad, Bacillus and Arthrobacter species, as well as a less common Staphylococcus inhabitant. Bacillus pumilus, Staphyloccocus equorum, Arthrobacter bergei and Pseudomonas marginalis strains have not been previously described as phytate‐degrading. Each site along the transect – from manure pile to receiving sediment – was host to a population of bacteria that can degrade phytate and hence, each is a possible non‐point source of orthophosphate pollution. Each new isolate could provide an enzyme additive for monogastric feed, thus reducing the impact of excessive phytate load on the environment.
Dementia Poststroke
Authors: Pohjasvaara Tarja , Vataja Risto , Leppävuori Antero , Erkinjuntti Timo 
Published: August 2007

Abstract: The frequency of dementia poststroke is high, and stroke considerably increases the risk of dementia. The risk factors for dementia related to stroke are still incompletely understood. In addition to age and low level of education, different combinations of vascular risk factors and stroke features have been associated with poststroke dementia. A single explanation for poststroke dementia is not adequate; rather, multiple factors including stroke features (dysphasia, major dominant stroke syndrome), infarct features (type, side, site, number, and volume), extent and type of white matter lesions (WMLs), degree and site of atrophy, host characteristics (e.g. age, educational level), and risk factors for stroke (e.g. prior cerebrovascular disease, diabetes) each contribute to the risk of dementia poststroke.Dementia after first ever clinical stroke is also frequent. Cognitive decline is present prior to stroke in up to one‐third of patients developing post‐stroke dementia. Medial temporal lobe atrophy, a marker of an increased risk of Alzheimer's disease (AD), is more frequent in stroke patients who have preexisting dementia or cognitive decline, as well as poststroke dementia. This may be explained by co‐existing AD and cerebrovascular disease (CVD). The magnitude of this mixed dementia (AD with CVD/Vascular Dementia (VaD)) group has been previously underestimated, and it is a diagnostic challenge in the older population.Dementia due to CVD is a rather advanced stage of is chemic brain changes, and outcome of treatment and prevention may be limited. Accordingly, the focus should be placed on the entire spectrum of cognitive impairment related to CVD, focusing especially the early cognitive changes.
No Association between Presenilin 1 Intron Gene or Butyrylcholinesterase K Variant and Alzheimer's Disease in Japanese Populations
Authors: Yamamoto Yasuji , Sengo Masahito , Yasuda Minoru , Maeda Kiyoshi 
Published: August 2007

Background: One of the purposes of this study was to examine whethe apolipoprotein E (ApoE) ɛ4 allele as a risk factor for Alzheimer's disease (AD) may be associated with the higher prevalence of AD in women compared with men. Recently, the polymorphic K variant of the butyrylcholinest erase (BChE‐K) gene and presenilin 1 (PS1) intronic polymorphism have been reported to be associated with AD respectively. Thus we have reexamined the frequency of BChE‐K, PS1 intronic polymorphism, and the ApoE ɛ4 allele in a large series of Japanese AD patients and controls. Methods: We have genotyped a large series of Japanese AD and age‐and sex‐matched controls by the method of polymerase chain reaction and restriction fragment length polymorphism for ApoE, BChE‐K, and PS1 intronic polymorphism. Results: The frequency of ApoE ɛ4 allele was significantly higher in AD patients than in controls, confirming the previous reports. In comparison between men and women, the number of individuals carrying one ɛ4 allele was much greater in women with AD than in men with this illness. Kaplan‐Meier analyses, plotting the ɛ4 gene doses against age of onset for men and women, revealed significant differences in age‐of‐onset curves between men and women.
Dementia in Parkinson's Disease: Its Incidence and a Possible Relationship with Dopa‐refractory Symptoms
Authors: Takeda Atsushi , Fujihara Kanae , Kikuchi Akio , Kimpara Teiko , Itoyama Yasuto 
Published: August 2007

Background: The diagnostic criteria for dementia in idiopathic Parkinson's disease (PD) remain controversial. In PD, general intelligence is relatively spared, although executive function is commonly impaired. Methods: Following the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM‐IV), in this study we defined dementia in PD as a combined impairment of memory and executive function, and evaluated its incidence and its relationship with other clinical features. Results: The prevalence of dementia among patients with PD was estimated to be 20–30% in an outpatient clinic and was found to be associated with the severity of motor impairments, especially Dopa‐refractory symptoms. On the other hand, no relationships were observed between the prevalence of dementia and patient age or age of onset. Conclusion: These data suggest that cognitive deficits, comprising dementia syndrome in PD, are mainly due to common neurodegenerative processes of non‐dopaminergic systems, but not to other concomitant diseases, such as Alzheimer's disease.
Effect of Presenilin 1 Missense Mutation and Aluminum on Early Neuronal Development of the Mouse Brain
Authors: Fukusho Eriko , Nakamura Yu , Kashiwagi Yujiro , Kudo Takashi , Tanaka Toshihisa , Matsumoto Naohiko , Kida Tomoyuki , Nakano Yuka , Shinosaki Kazuhiro , Takeda Masatoshi 
Published: August 2007

Background: The pathology of Alzheimer's disease (AD) has not been fully elucidated. Presenilin 1 (PS1) mutation is one of the major genetic factors of AD, while aluminum is a candidate for the environmental risk factor. Methods: First, we investigated the influence of PS1 mutation on the neuronal development in ‘knock‐in’ mice of PS1 1213T mutation. Next, the effect of prenatal exposure to aluminum on the neuronal development of the knock‐in mice was examined. Results: In the newborns with the mutated PS1 allele, a tendency of delayed neurological development was seen and an abnormal distribution of neurofilaments was found, implying that the PS1 mutation might alter early neuronal development. Intraperitoneal administration of aluminum‐maltol resulted in the increase of aluminum in brain tissues of newborns, and in abnormal distribution of neurofilaments. Furthermore, the PS1 mutation promoted a change in neurofilament distribution induced by exposure to aluminum. Conclusion: Thus, PS1 mutation and aluminum are suggested to affect early neuronal development, as reflected in some aspects of the pathology of AD.
Interrater Reliability of the Todai‐shiki Observational Rating Scale (TORS) for Group Psychotherapy of Elderly Patients with Dementia
Authors: Matsuda Osamu , Kurokawa Yukiko , Saito Masahiko , Maruyama Kaori , Miyamoto Noriko 
Published: August 2007

Background: Various types of psychosocial approaches have been developed in the field of dementia patient care. One of these approaches, reminiscence groups, is often applied in the care setting. We developed the Todai‐shiki Observational Rating Scale (TORS) to assess the effectiveness of reminiscence groups, and we examined its interrater reliability in this preliminary study. Methods: The subjects of the study were nine elderly patients with mild to moderate dementia. The TORS consists of 20 items covering four aspects of the patients' clinical picture: verbal communication, nonverbal communication, attention and interest, and emotion. The intraclass correlation coefficient (ICC) for each item was calculated. The mean ICCs for each item over five sessions were used as a reliable index. Results: The mean ICCs ranged from 0.53 to 1.00, and averaged 0.83. Conclusion: This preliminary study suggested that the TORS might be a useful tool to evaluate the effects of group psychotherapy for patients with dementia.
Pathology in Senile Patients with Abnormal Body Sensation
Authors: Takahashi Tohru , Tamaru Tsunemi , Imai Junko , Washizuka Shinsuke , Ozawa Hiroshi , Harada Yuzuru , Morishima Akihito , Amano Naoji 
Published: August 2007

Background: Senile people tend to develop abnormal body sensations such as delusion of parasitosis. To discuss the pathology of senile abnormal body sensation, we studied patients with abnormal body sensation, cenesthopathy, and delusion of parasitosis and investigated their age and gender. Methods: The subjects were a mix of patients reported in Japan and our patients. They were classified into two groups; Group 1 were those with a condition considered to be a somatoform disorder and Group 2 were those with a delusion of parasitosis and chronic tactile hallucinosis. Results: Group 1 consisted of 29 patients aged 46.4±9.6 years; the male:female ratio was 1:4.8. Group 2 consisted of 51 patients aged 65.8±9.4 years; the male:female ratio was 1:1.125. Conclusion: Based on the age tendency characteristics, Group 1 was called the involutional group and Group 2 the senile group. The age and gender distribution in the involutional group (Group 1) may be related mainly to climacteric disorders and suggested some influences of climacteric changes on the appearance of abnormal body sensation. On the other hand, the pathology in the senile group (Group 2) appeared to be associated with senile organic changes in addition to climacteric changes and sensory changes of skin and mucosal area during the involutional period.