bluuebunny/crossref_metadata_2025_split huggingface dataset:
The individual and combined influence of HIV and hepatitis C virus on dyslipidaemia in a high‐risk Hispanic population
Authors: Forrester JE , McGovern BH , Rhee MS , Sterling RK 
Published: June 2009

ObjectivesTo assess the effects of chronic hepatitis C (HCV) and HIV infection on dyslipidaemia in a Hispanic population at high risk of insulin resistance.MethodsWe compared serum lipids and C‐reactive protein (CRP) in 257 Hispanic adults including 47 HIV‐ mono‐infected, 43 HCV‐mono‐infected and 59 HIV/HCV‐co‐infected individuals as well as 108 healthy controls. We also assessed the effect of HCV on lipid alterations associated with antiretroviral therapy (ART), and the impact of HCV and HIV on the associations among insulin resistance, triglycerides and cholesterol.ResultsHCV infection was associated with lower total and low‐density lipoprotein (LDL) cholesterol, but not high‐density lipoprotein (HDL) cholesterol or triglycerides compared with healthy controls. HIV infection was associated with higher triglycerides and lower HDL, but not total or LDL cholesterol. HCV mitigated the elevation of triglycerides associated with ART. In healthy Hispanic adults, insulin resistance was significantly correlated with higher triglycerides, CRP and lower HDL. HIV infection nullified the association of insulin resistance with triglycerides and HDL, and the association of triglycerides with LDL. HCV infection nullified the association of insulin resistance with triglycerides, HDL and CRP.ConclusionsHCV co‐infection alters the profile of HIV‐associated dyslipidaemia. The clinical significance of these findings for cardiovascular complications in HIV merits further study.
Paradoxical effect of ethanol on potassium channel currents and cell survival in cerebellar granule neurons
Authors: Lefebvre Thomas , Gonzalez Bruno J. , Vaudry David , Desrues Laurence , Falluel‐Morel Antony , Aubert Nicolas , Fournier Alain , Tonon Marie‐Christine , Vaudry Hubert , Castel Hélène 
Published: May 2009

AbstractTransient exposure to ethanol (EtOH) results in a massive neurodegeneration in the developing brain leading to behavioral and cognitive deficits observed in fetal alcohol syndrome. There is now compelling evidence that K+channels play an important role in the control of programmed cell death. The aim of the present work was to investigate the involvement of K+channels in the EtOH‐induced cerebellar granule cell death and/or survival. At low and high concentrations, EtOH evoked membrane depolarization and hyperpolarization, respectively. Bath perfusion of EtOH (10 mM) depressed theIA(transient K+current) potassium current whereas EtOH (400 mM) provoked a marked potentiation of the specificIK(delayed rectifier K+current) current. Pipette dialysis with GTPγS or GDPβS did not modify the effects of EtOH (400 mM) on both membrane potential andIKcurrent. In contrast, the reversible depolarization and slowly recovering inhibition ofIAinduced by EtOH (10 mM) became irreversible in the presence of GTPγS. EtOH (400 mM) induced prodeath responses whereas EtOH (10 mM) and K+channel blockers promoted cell survival. Altogether, these results indicate that in cerebellar granule cells, EtOH mediates a dual effect on K+currents partly involved in the control of granule cell death.
Characterization of prion protein‐enriched domains, isolated from rat cerebellar granule cells in culture
Authors: Farina Francesca , Botto Laura , Chinello Clizia , Cunati Diana , Magni Fulvio , Masserini Massimo , Palestini Paola 
Published: May 2009

AbstractThe biological functions of prion protein (PrPC) and its possible interaction with other specific molecular membrane partners remain largely unknown. The aim of this study is to gain information on the molecular environment of PrPC by analyzing the lipid and protein composition of a PrPC‐enriched membrane subfraction, called prion domain, PrD. This domain was obtained by immunoprecipitation of detergent‐resistant microdomains (DRM) of rat cerebellar granule cells under conditions designed to preserve lipid‐mediated membrane organization. The electrophoretic pattern of PrD, after staining with Coomassie blue, showed the enrichment of some protein bands in comparison with DRM. μLiquid cromatography‐electrospray ionization‐mass spectrometry (μLC‐ESI‐MS)/MS analysis showed that Thy‐1 and different types of myosin were strongly enriched in PrD and, in a lesser extent, also OBCAM, LSAMP and tubulin, present altogether in a single band. Experiments using the chemical cross‐linker BS3 suggested the existence of an interaction between PrPC and neural cell adhesion molecule (NCAM). Concerning lipids, the comparison between PrD and DRM showed a similar phospholipid/sphingolipid ratio, a phospholipid/cholesterol ratio doubled, and a strong decrease of plasmenilethanolamine (19.7 ± 3.5% vs. 38.3 ± 1.2%). In conclusion, the peculiar lipid composition and in particular the presence of proteins involved in synaptic plasticity, cell adhesion, cytoskeleton regulation and signalling, suggest an important physiological role in neurons of Prion Domain.
On the mechanism of oleate transport across human brain microvessel endothelial cells
Authors: Mitchell Ryan W. , Edmundson Carmen L. , Miller Donald W. , Hatch Grant M. 
Published: May 2009

AbstractThe blood–brain barrier formed by the brain capillary endothelial cells provides a protective barrier between the systemic blood and the extracellular environment of the CNS. As most fatty acids in the brain enter from the blood, we examined the mechanism of oleate (C18:1) transport across primary human brain microvessel endothelial cells (HBMEC). The permeability of [1‐14C]oleate was determined using confluent cells grown on Transwell® inserts in both the absence or presence of bovine serum albumin in the basolateral media, and following inhibition of various fatty acid transporters. The passage of [1‐14C]oleate across confluent HBMEC monolayers was significantly enhanced when fatty acid free albumin was present in the basolateral media. The presence of the non‐specific fatty acid uptake inhibitor phloretin significantly decreased [1‐14C]oleate uptake by HBMEC and the subsequent release of [1‐14C]oleate into the basolateral medium. Knockdown of fatty acid transport protein‐1 or fatty acid translocase/CD36 significantly decreased [1‐14C]oleate transport across the HBMEC monolayer from either apical as well as basolateral sides. The findings indicate that a fatty acid acceptor is a requirement for oleate transport across HBMEC monolayers. In addition, transport of oleate across HBMEC is, in part, a transcellular process mediated by fatty acid transport proteins.
Varying survival of motoneurons and activation of distinct molecular mechanism in response to altered peripheral myelin protein 22 gene dosage
Authors: Nattkämper Heiner , Halfter Hartmut , Khazaei Mohammad R. , Lohmann Tina , Gess Burkhard , Eisenacher Martin , Willscher Edith , Young Peter 
Published: May 2009

AbstractAlteration in the expression level of peripheral myelin protein 22 (PMP22) is the most frequent cause for demyelinating neuropathies of Charcot‐Marie‐Tooth type. Here, we demonstrate a loss of motoneurons (MNs) in the spinal cords from transgenic mice over‐expressing Pmp22 (Pmp22tg) while mice lacking Pmp22 [Pmp22ko; knockout (ko)] exhibited normal MN numbers at the symptomatic age of 60 days. In order to describe the molecular changes in affected MNs, these cells were isolated from lumbar spinal cords by laser‐capture microdissection. Remarkably, the MNs of the Pmp22ko and Pmp22tg mice showed different expression profiles because of the altered Pmp22 expression. The changes in the expression profile of MNs from Pmp22ko mice resemble those described in MNs from mice after nerve injury and included genes that had been described in neuronal growth and regeneration like Gap43 and Sprr11a. The changes detected in the expression pattern of MNs from Pmp22tg mice exhibited fewer similarities to other expression patterns. The specific expression pattern in the MNs of the Pmp22ko mice might contribute to the better survival of the MNs. Our study also revealed induction of genes like brain‐expressed X‐linked 1 (Bex1) and desmoplakin (Dsp) that had recently been found up‐regulated in MNs of human amyotrophic lateral sclerosis patients.
Brain‐derived neurotrophic factor facilitates maturation of mesenchymal stem cell‐derived dopamine progenitors to functional neurons
Authors: Trzaska Katarzyna A. , King Cecile C. , Li Ke‐Yong , Kuzhikandathil Eldo V. , Nowycky Martha C. , Ye Jiang‐Hong , Rameshwar Pranela 
Published: May 2009

AbstractThe generation of dopamine (DA) neurons from stem cells holds great promise in the treatment of Parkinson’s disease and other neural disease associated with dysfunction of DA neurons. Mesenchymal stem cells (MSCs) derived from the adult bone marrow show plasticity with regards to generating cells of other germ layers. In addition to reduced ethical concerns, MSCs could be transplanted across allogeneic barriers, making them desirable stem cells for clinical applications. We have reported on the generation of DA cells from human MSCs using sonic hedgehog (SHH), fibroblast growth factor 8 and basic fibroblast growth factor. Despite the secretion of DA, the cells did not show evidence of functional neurons, and were therefore designated DA progenitors. Here, we report on the role of brain‐derived neurotrophic factor (BDNF) in the maturation of the MSC‐derived DA progenitors. 9‐day induced MSCs show significant tropomyosin‐receptor‐kinase B expression, which correlate with its ligand, BDNF, being able to induce functional maturation. The latter was based on Ca2+ imaging analyses and electrophysiology. BDNF‐treated cells showed the following: increases in intracellular Ca2+ upon depolarization and after stimulation with the neurotransmitters acetylcholine and GABA and, post‐synaptic currents by electrophysiological analyses. In addition, BDNF induced increased DA release upon depolarization. Taken together, these results demonstrate the crucial role for BDNF in the functional maturation of MSC‐derived DA progenitors.
Sphingosine‐1‐phosphate receptors mediate neuromodulatory functions in the CNS
Authors: Sim‐Selley Laura J. , Goforth Paulette B. , Mba Mba U. , Macdonald Timothy L. , Lynch Kevin R. , Milstien Sheldon , Spiegel Sarah , Satin Leslie S. , Welch Sandra P. , Selley Dana E. 
Published: May 2009

AbstractSphingosine‐1‐phosphate (S1P) is a ubiquitous, lipophilic cellular mediator that acts in part by activation of G‐protein‐coupled receptor. Modulation of S1P signaling is an emerging pharmacotherapeutic target for immunomodulatory drugs. Although multiple S1P receptor types exist in the CNS, little is known about their function. Here, we report that S1P stimulated G‐protein activity in the CNS, and results from [35S]GTPγS autoradiography using the S1P1‐selective agonist SEW2871 and the S1P1/3‐selective antagonist VPC44116 show that in several regions a majority of this activity is mediated by S1P1receptors. S1P receptor activation inhibited glutamatergic neurotransmission as determined by electrophysiological recordings in cortical neuronsin vitro, and this effect was mimicked by SEW2871 and inhibited by VPC44116. Moreover, central administration of S1P producedin vivoeffects resembling the actions of cannabinoids, including thermal antinociception, hypothermia, catalepsy and hypolocomotion, but these actions were independent of CB1receptors. At least one of the central effects of S1P, thermal antinociception, is also at least partly S1P1receptor mediated because it was produced by SEW2871 and attenuated by VPC44116. These results indicate that CNS S1P receptors are part of a physiologically relevant and widespread neuromodulatory system, and that the S1P1receptor contributes to S1P‐mediated antinociception.
A lipohydroxyacid‐containing shampoo improves scalp condition and quality of life in patients with seborrheic dermatitis and light‐to‐moderate scalp psoriasis
Authors: Seité S , Paries J , Reygagne P , Hamidou Z , Jouanique C , Perez‐Pala G , Rougier A 
Published: June 2009

SummaryBackground  Dandruff is a common scalp disorder affecting almost half of the post‐pubertal population of any ethnicity and both genders. It is one of the major reasons for patients to consult a dermatologist and it is the cause of significant psychological and social distress.Aims  The aim of this open study was to evaluate the benefit of a 4‐week treatment with a shampoo containing 0.1% lipohydroxyacid (LHA) and 1.3% salicylic acid on the scalp condition and on the quality of life of 275 volunteers with seborrheic dermatitis (SD) (n = 226) or light‐to‐moderate scalp psoriasis (SP) (n = 49).Methods  The clinical benefit of the treatment was assessed by scoring the following parameters, i.e., severity of the dermatosis, scaling, itching, excoriations, and superficial burning sensation. The impact on the quality of life was assessed using the Scalpdex, a questionnaire specially developed by Chen et al. for patients with scalp dermatitis, which includes 23 questions regarding the symptoms, functioning and emotions affected by scalp dermatosis.Results  The shampoo used in this study was well tolerated. After a 4‐week treatment, dermatologists noticed a significant clinical improvement of all the scalp parameters evaluated (i.e., the composite lesional score was improved in 91% and 77% of the patients with SD or SP respectively). The symptoms, functioning and emotions scores of quality of life were also significantly improved in relation to the improvement of scalp condition.Conclusion  This study not only allowed a better understanding of the SD and SP patient’s profile but also demonstrated that the shampoo evaluated is a convenient, efficient, safe, and well‐tolerated cosmetic treatment of SD and light‐to‐moderate SP improving greatly the quality of life of the treated patients.
Silicone migration and granuloma formation
Authors: Altmeyer Mary D , Anderson Lisa L , Wang Alun R 
Published: June 2009

SummaryThe use of liquid injectable silicone for soft tissue augmentation is a controversial practice within the medical community. Injectable silicone has been illegally obtained, adulterated, and abused by nonmedical practitioners for the last five decades. Injection of silicone can result in catastrophic consequences including death, when grossly abused. Opponents of this practice cite the many serious adverse events that have occurred with its use both legally and illegally. Proponents argue that employment of a stringent regimen of use as well as a highly purified medical grade product allow for a safe utilization of the material. Both sides agree that this practice calls for a high degree of knowledge and technical skill. A continued evaluation of the long‐term safety of this material is necessary before a consensus can be reached.Herein, we report a case of illegal administration of injectable silicone resulting in product migration accompanied by a granulomatous response. Further, the literature that both supports and refutes the practice of silicone injection is reviewed.
The low abundance of clonally expanded mitochondrial DNA point mutations in aged substantia nigra neurons
Authors: Reeve Amy K. , Krishnan Kim J. , Taylor Geoffrey , Elson Joanna L. , Bender Andreas , Taylor Robert W. , Morris Christopher M. , Turnbull Doug M. 
Published: May 2009

SummaryClonally expanded mitochondrial DNA (mtDNA) deletions accumulate with age in human substantia nigra (SN) and high levels cause respiratory chain deficiency. In other human tissues, mtDNA point mutations clonally expand with age. Here, the abundance of mtDNA point mutations within single SN neurons from aged controls was investigated. From 31 single cytochrome c oxidase normal SN neurons, only one clonally expanded mtDNA point mutation was identified, suggesting in these neurons mtDNA point mutations occur rarely, whereas mtDNA deletions are frequently observed. This contrasts observations in mitotic tissues and suggests that different forms of mtDNA maintenance may exist in these two cell types.
Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity
Authors: Pawlikowska Ludmila , Hu Donglei , Huntsman Scott , Sung Andrew , Chu Catherine , Chen Justin , Joyner Alexander H. , Schork Nicholas J. , Hsueh Wen‐Chi , Reiner Alexander P. , Psaty Bruce M. , Atzmon Gil , Barzilai Nir , Cummings Steven R. , Browner Warren S. , Kwok Pui‐Yan , Ziv Elad ,   for the Study of Osteoporotic Fractures
Published: May 2009

SummaryThe insulin/IGF1 signaling pathways affect lifespan in several model organisms, including worms, flies and mice. To investigate whether common genetic variation in this pathway influences lifespan in humans, we genotyped 291 common variants in 30 genes encoding proteins in the insulin/IGF1 signaling pathway in a cohort of elderly Caucasian women selected from the Study of Osteoporotic Fractures (SOF). The cohort included 293 long‐lived cases (lifespan ≥ 92 years (y), mean ± standard deviation (SD) = 95.3 ± 2.2y) and 603 average‐lifespan controls (lifespan ≤ 79y, mean = 75.7 ± 2.6y). Variants were selected for genotyping using a haplotype‐tagging approach. We found a modest excess of variants nominally associated with longevity. Nominally significant variants were then replicated in two additional Caucasian cohorts including both males and females: the Cardiovascular Health Study and Ashkenazi Jewish Centenarians. An intronic single nucleotide polymorphism in AKT1, rs3803304, was significantly associated with lifespan in a meta‐analysis across the three cohorts (OR = 0.78 95%CI = 0.68–0.89, adjusted P = 0.043); two intronic single nucleotide polymorphisms in FOXO3A demonstrated a significant lifespan association among women only (rs1935949, OR = 1.35, 95%CI = 1.15–1.57, adjusted P = 0.0093). These results demonstrate that common variants in several genes in the insulin/IGF1 pathway are associated with human lifespan.
A syngeneic glioma model to assess the impact of neural progenitor target cell age on tumor malignancy
Authors: Mikheev Andrei M. , Stoll Elizabeth A. , Mikheeva Svetlana A. , Maxwell John‐Patrick , Jankowski Pawel P. , Ray Sutapa , Uo Takuma , Morrison Richard S. , Horner Philip J. , Rostomily Robert C. 
Published: May 2009

SummaryHuman glioma incidence, malignancy, and treatment resistance are directly proportional to patient age. Cell intrinsic factors are reported to contribute to human age‐dependent glioma malignancy, but suitable animal models to examine the role of aging are lacking. Here, we developed an orthotopic syngeneic glioma model to test the hypothesis that the age of neural progenitor cells (NPCs), presumed cells of glioma origin, influences glioma malignancy. Gliomas generated from transformed donor 3‐, 12‐, and 18‐month‐old NPCs in same‐aged adult hosts formed highly invasive glial tumors that phenocopied the human disease. Survival analysis indicated increased malignancy of gliomas generated from older 12‐ and 18‐month‐old transformed NPCs compared with their 3‐month counterparts (median survival of 38.5 and 42.5 vs. 77 days, respectively). This study showed for the first time that age of target cells at the time of transformation can affect malignancy and demonstrated the feasibility of a syngeneic model using transformed NPCs for future examination of the relative impacts of age‐related cell intrinsic and cell‐extrinsic factors in glioma malignancy.
Endogenous cGMP regulates adult longevity via the insulin signaling pathway in Caenorhabditis elegans
Authors: Hahm Jeong‐Hoon , Kim Sunhee , Paik Young‐Ki 
Published: May 2009

SummaryG‐proteins, including GPA‐3, play an important role in regulating physiological responses in Caenorhabditis elegans. When confronted with an environmental stimulus such as dauer pheromone, or poor nutrients, C. elegans receives and integrates external signals through its nervous system (i.e. amphid neurons), which interprets and translates them into biological action. Here it is shown that a suppressed neuronal cGMP level caused by GPA‐3 activation leads to a significant increase (47.3%) in the mean lifespan of adult C. elegans through forkhead transcription factor family O (FOXO)‐mediated signal. A reduced neuronal cGMP level was found to be caused by an increased cGMP‐specific phosphodiesterase activity at the transcriptional level. Our results using C. elegans mutants with specific deficits in TGF‐β and FOXO RNAi system suggest a mechanism in that cGMP, TGF‐β, and FOXO signaling interact to differentially produce the insulin‐like molecules, ins‐7 and daf‐28, causing suppression of the insulin/IGF‐1 pathway and promoting lifespan extension. Our findings provide not only a new mechanism of cGMP‐mediated induction of longevity in adult C. elegans but also a possible therapeutic strategy for neuronal disease, which has been likened to brain diabetes.
Documentation of Istanbul Historic Peninsula by Kinematic Terrestrial Laser Scanning
Authors: Kersten Thomas P. , Büyüksalİh Gürcan , Baz İBrahİm , Jacobsen Karsten 
Published: June 2009

AbstractAlthough the Historic Peninsula of old Istanbul was added to the UNESCO World Heritage List in 1985, complete documentation of this important area has not yet been carried out. In 2006 the Istanbul Metropolitan Municipality’s Historical Environment Protection Directorate initiated the “Historic Peninsula Project”, which covers an area of 1500 ha and includes approximately 48 000 buildings in crowded and frequently narrow streets. BİMTAŞ, a company owned by the Municipality, immediately started the documentation of all buildings in the project area using terrestrial laser scanning. This created the challenge of building up an efficient production environment with new high‐end technology to fulfil the requirements of this project in a very short timeframe of 2 years. This paper describes the entire production environment for documentation of all buildings, detailing the frequent adaptations of the process resulting from learning on the job. Although the data acquisition and mapping environment was established in the course of production, it was always essential to optimise the technical solutions in order to meet the requirements for data quality and delivery deadlines. Only 80 ha of the required 1500 ha was completed using static scanning during the first 6 months, thus requiring a change from static to mobile terrestrial laser scanning in order to accelerate the work and to conclude the scanning phase for the remaining major area within 3 months.