bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of the ecto‐ATPase NTPDase2 with glial cells of the peripheral nervous system
Authors: Braun Norbert , Sévigny Jean , Robson Simon C. , Hammer Klaus , Hanani Menachem , Zimmermann Herbert 
Published: January 2004

AbstractCellular signaling via extracellular nucleotides appears to play a major role in the functioning of the peripheral nervous system. Information regarding the functional characterization of nucleotide P2 receptors or their expression pattern has been accumulating rapidly; however, very little is known regarding the distribution of ecto‐nucleotidases in the periphery. The extracellular level of nucleotides is controlled by ecto‐nucleotidases, whereby the three membrane‐bound members of the ecto‐nucleoside triphosphate diphosphohydrolase (E‐NTPDase) family are of special functional importance. Using enzyme histochemistry and immunostaining, we demonstrate that NTPDase2 is associated with nonmyelinating Schwann cells of the rat sciatic nerve, whereas NTPDase1 is restricted to blood vessel walls. NTPDase2 immunoreactivity was detected from embryonic day E18 onward, suggesting that immature Schwann cells express the enzyme. With the onset of myelination, NTPDase2 immunoreactivity remained associated solely with nonmyelinating Schwann cells. NTPDase2 was absent from perisynaptic Schwann cells but was associated with fibroblasts covering the endplate at some distance. In addition, NTPDase2 immunoreactivity was associated with the satellite glial cells in dorsal root ganglia and sympathetic ganglia, and with the enteric glia surrounding the cell bodies of ganglionic neurons of the myenteric and the submucous plexus. In contrast to NTPDase1, NTPDase2 preferentially hydrolyzes nucleoside triphosphates over nucleoside diphosphates and thus can act either in inactivating or in producing P2 receptor ligands. Our results suggest that NTPDase2 plays an important role in the control of nucleotide‐mediated activation of peripheral neurons or glia and in the dialogue between these two cell types. © 2003 Wiley‐Liss, Inc.
Activated glia induce neuron death via MAP kinase signaling pathways involving JNK and p38
Authors: Xie Zhong , Smith Carolyn J. , Van Eldik Linda J. 
Published: January 2004

AbstractChronic glial activation in neurodegenerative diseases contributes to neuronal dysfunction and neuron loss through production of neuroinflammatory molecules. However, the molecular mechanisms, particularly the signal transduction pathways involved in glia‐dependent neuron death, are poorly understood. As a first step to address this question, we used a neuron‐glia co‐culture system that allows diffusion of soluble molecules between glia and neurons to test the potential importance of mitogen‐activated protein kinase (MAPK) signaling pathways in the glia‐induced neuron death. Activation of glia in co‐culture by lipopolysaccharide (LPS) induced apoptotic‐like neuron death. The MAPKs tested (p38, JNK, ERK1/2) were activated in both glia and neurons following LPS treatment, suggesting their involvement in both glial activation and neuronal response to diffusible, glia‐derived neurotoxic molecules. Inhibitors of p38 and JNK partially blocked neuron death in the LPS‐treated co‐culture, whereas an ERK1/2 pathway inhibitor did not protect neurons. These results show that p38 and JNK MAPKs, but not ERK1/2 MAPK, are important signal transduction pathways contributing to glia‐induced neuron death. © 2003 Wiley‐Liss, Inc.
Cloning, transport properties, and differential localization of two splice variants of GLT‐1 in the rat CNS: Implications for CNS glutamate homeostasis
Authors: Sullivan Robert , Rauen Thomas , Fischer Frauke , Wießner Michael , Grewer Christof , Bicho Ana , Pow David V. 
Published: January 2004

AbstractAt least two splice variants of GLT‐1 are expressed by rat brain astrocytes, albeit in different membrane domains. There is at present only limited data available as to the spatial relationship of such variants relative to the location of synapses and their functional properties. We have characterized the transport properties of GLT‐1v in a heterologous expression system and conclude that its transport properties are similar to those of the originally described form of GLT‐1, namely GLT‐1α. We demonstrate that GLT‐1α is localized to glial processes, some of which are interposed between multiple synapse types, including GABAergic synapses, whereas GLT‐1v is expressed by astrocytic processes, at sites not interposed between synapses. Both splice variants can be expressed by a single astrocyte, but such expression is not uniform over the surface of the astrocytes. Neither splice variant of GLT‐1 is evident in brain neurons, but both are abundantly expressed in some retinal neurons. We conclude that GLT‐1v may not be involved in shaping the kinetics of synaptic signaling in the brain, but may be critical in preventing spillover of glutamate between adjacent synapses, thereby regulating intersynaptic glutamatergic and GABAergic transmission. Furthermore, GLT‐1v may be crucial in ensuring that low levels of glutamate are maintained at extrasynaptic locations, especially in pathological conditions such as ischemia, motor neurone disease, and epilepsy. © 2003 Wiley‐Liss, Inc.
Downregulation of steroidogenic acute regulatory protein (StAR) gene expression by cyclic AMP in cultured Schwann cells
Authors: Benmessahel Yasmina , Troadec Jean‐Denis , Cadepond Françoise , Guennoun Rachida , Hales Dale Buchanan , Schumacher Michael , Groyer Ghislaine 
Published: January 2004

AbstractSteroidogenic acute regulatory protein (StAR) plays a key role in the availability of cholesterol to the inner mitochondrial membrane, where the first step of steroidogenesis, its conversion to pregnenolone, takes place. Here, we demonstrate for the first time that the StAR gene is also expressed in the rat sciatic nerve and in cultured Schwann cells. The addition to the culture medium of the cAMP‐elevating agent forskolin or of the cAMP analogue 8Br‐cAMP produced a time‐course extinction of StAR gene expression. An inverse relationship was demonstrated between StAR gene expression and the intracellular cAMP content. Accordingly, pharmacological inhibition of the activities of Schwann cell adenylyl cyclase or of phosphodiesterase IV resulted in modifications of StAR gene expression. Since StAR gene expression is stimulated by cAMP in classical steroidogenic cells, our work is the first demonstration of a negative regulation of StAR gene by cAMP. © 2003 Wiley‐Liss, Inc.
Sulfatide is a negative regulator of oligodendrocyte differentiation: Development in sulfatide‐null mice
Authors: Hirahara Yukie , Bansal Rashmi , Honke Koichi , Ikenaka Kazuhiro , Wada Yoshinao 
Published: January 2004

AbstractGalactosylceramide (GalC) and its sulfated analogue, sulfatide, are major galactosphingolipid components of myelin and oligodendrocyte plasma membranes in the nervous system. We previously hypothesized that these galactolipids play functional roles in the regulation of oligodendrocyte terminal differentiation by acting as sensors/transmitters of environmental information. Evidence strongly supports this idea. First, these molecules are initially expressed on the cell surface at the interface at which oligodendrocyte progenitors first enter terminal differentiation. Second, exposure of oligodendrocyte progenitors to anti‐GalC/‐sulfatide (RmAb) or antisulfatide (O4), but not anti‐GalC (O1), antibodies leads to the reversible arrest of oligodendrocyte lineage progression at this interface. Third, in cerebroside galactosyl transferase‐null mice (Cgt−/−) that are unable to synthesize either GalC or sulfatide, terminal differentiation and morphological maturation of oligodendrocytes are enhanced. In the present study, we examined oligodendrocytes differentiation in cerebroside sulfotransferase‐null mice (Cst−/−) that lack sulfatide but express GalC. We show that cerebroside sulfotransferase mRNA expression begins already in the embryonic spinal cord and progressively increases with age, that the late progenitor marker POA is not synthesized in the absence of this enzyme, and that, most notably, there is a two‐ to threefold enhancement in the number of terminally differentiated oligodendrocytes both in culture and in vivo, similar to that in mice lacking both GalC and sulfatide. We conclude that primarily sulfatide, rather than GalC, is a key molecule for the negative regulation of oligodendrocyte terminal differentiation. © 2003 Wiley‐Liss, Inc.
Glial activation modulates glutamate neurotoxicity in cerebellar granule cell cultures
Authors: Pérez‐Capote Kamil , Serratosa Joan , Solà Carme 
Published: January 2004

AbstractWe studied the influence of glial cells on the neuronal response to glutamate toxicity in cerebellar granule cell cultures. We compared the effect of glutamate on neuronal viability in neuronal vs. neuronal‐glial cultures and determined this effect after pretreating the cultures with the lipopolysaccharide (LPS) of Escherichia coli, agent widely used to induce glial activation. Morphological changes in glial cells and nitric oxide (NO) production were evaluated as indicators of glial activation. We observed that glutamate neurotoxicity in neuronal‐glial cultures was attenuated in a certain range of glutamate concentration when compared to neuronal cultures, but it was enhanced at higher glutamate concentrations. This enhanced neurotoxicity was associated with morphological changes in astrocytes and microglial cells in the absence of NO production. LPS treatment induced morphological changes in glial cells in neuronal‐glial cultures as well as NO production. These effects occurred in the absence of significant neuronal death. However, when LPS‐pretreated cultures were treated with glutamate, the sensitivity of neuronal‐glial cultures to glutamate neurotoxicity was increased. This was accompanied by additional morphological changes in glial cells in the absence of a further increase in NO production. These results suggest that quiescent glial cells protect neuronal cells from glutamate neurotoxicity, but reactive glial cells increase glutamate neurotoxicity. Therefore, glial cells play a key role in the neuronal response to a negative stimulus, suggesting that this response can be modified through an action on glial cells. © 2003 Wiley‐Liss, Inc.
Cost‐effectiveness analysis and health care resource allocation: decision rules under variable returns to scale
Authors: Elbasha Elamin H. , Messonnier Mark L. 
Published: January 2004

AbstractWe argue that health programs are administered in settings that often violate the frequently stated assumption of constant returns to scale in the provision of health services. Three types of returns to scale are identified from the general economic literature: returns to scale with respect to population, effectiveness, and quality. We show that decision rules based on incremental cost‐effectiveness ratios or cost–benefit tests are not optimal if returns to scale are not constant. We derive the optimal decision rules under variable returns to scale using optimization techniques, and employ several examples to illustrate the concepts and methods. Published in 2003 by John Wiley & Sons, Ltd.
The value of risk‐free cigarettes – do smokers underestimate the risk?
Authors: Hammar Henrik , Johansson‐Stenman Olof 
Published: January 2004

AbstractThe health risk of smoking is valued using the contingent valuation method, applied to a Swedish sample of smokers. The respondents were asked to put a value on newly developed cigarettes with no associated health risks. The average additional willingness to pay for the new cigarettes is estimated to be between 10 and 41 SEK per pack, where the variation is due to statistical method, discounting, and whether the open‐ended or closed‐ended question format is used. Using medical data on life shortening effects of smoking, the results indicate rather low values put on a lost life‐year, compared to most existing estimates based on other methods. This may indicate that smokers do underestimate the health risk of smoking. There is also initial optimism‐bias regarding people's own ability to quit smoking at will. However, there are remaining methodological questions and we found little or no sensitivity to scope. Copyright © 2003 John Wiley & Sons, Ltd.
Responses to standard gambles: are preferences ‘well constructed’?
Authors: Baker Rachel , Robinson Angela 
Published: January 2004

AbstractStandard gamble (SG) is commonly used to elicit preferences in order to assess health related quality of life. There has been little qualitative research exploring how respondents answer such questions.An SG study was designed to elicit values for the health states associated with anti‐hypertensive medication, stroke and cardiovascular disease. This paper describes a qualitative study that was carried out alongside the SG exercise in order to document the thought processes respondents bring to bear in formulating their responses. Data were generated using ‘think aloud’ techniques and semi‐structured interviews. Values were generally well‐constructed: responses were thoroughly considered, and respondents made complex trade‐offs and arrived at a point of indifference. However, some respondents incorporated inappropriate information into their choices, redefining the hypothetical ‘Option B’ resulting in problems interpreting the probabilistic information. Consideration of non‐health factors was commonplace, in particular the impact of choices on others. We discuss these findings in terms of the use of qualitative methods in health economics and the wider discourse surrounding the theoretical underpinnings of health state valuation. Copyright © 2003 John Wiley & Sons, Ltd.
Cost‐effectiveness analysis based on the number‐needed‐to‐treat: common sense or non‐sense?
Authors: Sønbø Kristiansen Ivar , Gyrd‐Hansen Dorte 
Published: January 2004

AbstractThis paper explores and critically discusses some of the methodological limitations of using the number‐needed‐to‐treat (NNT) in economic evaluation. We argue that NNT may be a straightforward measure of benefit when the effect of an intervention is immediate, but that serious problems arise when the effect is delay rather than avoidance of an adverse event. In this case, NNT is not a robust or accurate measure of effect, but will vary considerably and inconsistently over time. This weakness will naturally spill over onto any CEA based on NNT. A literature review demonstrated that CEAs based on NNT were all published within the last five years, and that all studies suffered from important limitations. A major weakness of using NNT is the imposed restrictions on the outcome measure, which can only be strictly uni‐dimensional and non‐generic. Using NNT in economic evaluations is obtained at a cost in terms of both methodological shortcomings, and a reduced ability for such evaluations to serve as a useful tool in decision making processes. The use of NNT in economic evaluations might be better avoided.To every complicated question, there is a simple, straightforward, easy – and probably wrong answer (Occam's Sledgehammer). Copyright © 2003 John Wiley & Sons, Ltd.
Insomnia, biological clock, and the bedtime decision: an economic perspective
Authors: Yaniv Gideon 
Published: January 2004

AbstractWhile insomnia can be a symptom of numerous mental and physical illnesses, it is frequently diagnosed as a sleep disorder in its own right, caused mainly by stressful life events or by non‐synchronization of individuals' biological sleep–wake cycle with the one they choose to practice. Because of irregular work schedules, late‐night entertainment, or rapid crossing of several time zones, individuals might retire to bed earlier or later than their biological bedtime, experiencing difficulties in falling asleep. The present paper develops a simple economic model of the bedtime decision, viewing the individual as a rational decision‐maker who determines her insomnia level through consciously weighing the cost and benefit of deviating from her biological bedtime. The model is then used to examine the individual's response to stress, yielding a prediction which is consistent with observed behavior, although not with sleep therapists' recommendations. Finally, the model is applied to the case of transmeridian flights, explaining jet lag as a rational adjustment to a misalignment between the individual's slow‐to‐adapt internal clock and her external environment. Copyright © 2003 John Wiley & Sons, Ltd.
Simulation of a Hirschman–Herfindahl index without complete market share information
Authors: Nauenberg Eric , Alkhamisi Mahdi , Andrijuk Yuri 
Published: January 2004

AbstractThis paper utilizes maximum likelihood methods to simulate a Hirschman–Herfindahl index (HHI) for markets in which complete market share information is unavailable or delayed. Many jurisdictions either may be unable to administratively collect data or experience delays in collection that make data regarding turbulent markets of limited use. With the development of this method, regulatory authorities monitoring health‐care competition or health‐care firms can now use market surveys – in which reliable recall is often limited to the largest three or four firms – to produce an on‐the‐spot measure of market concentration. Copyright © 2003 John Wiley & Sons, Ltd.
Increasing patient choice in primary care: the management of minor ailments
Authors: Bojke Chris , Gravelle Hugh , Hassell Karen , Whittington Zoe 
Published: January 2004

AbstractWe examine the effects of an intervention to provide easier access to pharmacists for patients with minor ailments. The intervention allowed pharmacists to prescribe and dispense medicines currently limited to general practitioners (GPs) without patients losing their right to free prescriptions. We show that the total number of GP consultations was unaffected by the intervention but that the proportion which were for minor ailments decreased. We also use estimate multinomial models of patient choices between GP and pharmacies and find that the main determinant is the type of minor ailment. Distance appears to have no effect on patient choice. Copyright © 2003 John Wiley & Sons, Ltd.
The effects of higher cigarette prices on tar and nicotine consumption in a cohort of adult smokers
Authors: Farrelly M.C. , Nimsch C.T. , Hyland A. , Cummings M. 
Published: January 2004

AbstractThe objective of this paper is to estimate the demand for tar and nicotine in cigarettes as a function of cigarette prices in a cohort of cigarette 11 966 smokers followed for 5 years. Data for the analysis come from a longitudinal telephone survey of 11 966 smokers who were interviewed in 1988 and 1993 as part of the Community Intervention Trial for Smoking Cessation (COMMIT). Separate models are estimated for three age groups to account for differences in levels of addiction and brand loyalty across age. We found that smokers respond to higher cigarette prices by reducing the number of cigarettes smoked per day but also by switching to cigarettes that are higher in tar and nicotine per cigarette. Copyright © 2003 John Wiley & Sons, Ltd.
Oral mucositis: A challenging complication of radiotherapy, chemotherapy, and radiochemotherapy. Part 2: Diagnosis and management of mucositis
Authors: Scully Crispian , Epstein Joel , Sonis Stephen 
Published: January 2004

AbstractBackground.Oral mucositis is a common sequel of radiotherapy, chemotherapy, and radiochemotherapy in patients with cancer or patients requiring hemopoietic stem cell transplants. Mucositis has a direct and significant impact on the duration of disease remission and cure rates, because it is a treatment‐limiting toxicity. Mucositis also affects survival because of the risk of infection and has a significant impact on quality of life and cost of care.Methods.This article reviews publications on the diagnosis and management of oral mucositis accessible from a MEDLINE search using as key words mucositis, radiotherapy, chemotherapy, hemopoietic stem cell transplant, and oral.Conclusions.Conventional care of patients with mucositis is currently essentially palliative, with good oral hygiene, narcotic analgesics, and topical palliative mouth rinses. © 2004 Wiley Periodicals, Inc. Head Neck 26: 77–84, 2004
The expression of key cell cycle markers and presence of human papillomavirus in squamous cell carcinoma of the tonsil
Authors: Li Wei , Thompson Carol H. , Cossart Yvonne E. , O'Brien Christopher J. , McNeil Edward B. , Scolyer Richard A. , Rose Barbara R. 
Published: January 2004

AbstractBackground.Chemical carcinogens induce squamous cell carcinoma (SCC) of the head and neck by targeting the p53 and the retinoblastoma (pRb) pathways. Human papillomavirus (HPV) might have an etiologic role in these cancers at particular sites. Few studies have compared cell cycle protein expression in HPV‐positive and HPV‐negative tumors in this region.Methods.Fifty tonsil SCCs were analyzed for HPV by PCR and for expression of cell cycle proteins (p53, pRb, p16INK4A, p21CIP1/WAF1, p27KIP1, and cyclinD1) by immunohistochemistry.Results.HPV was present in 42%; almost all were type 16. There were statistical associations between HPV positivity and reduced expression of pRb and cyclinD1, overexpression of p16, and younger patient age. Tumor with down‐regulated p27 tended to have down‐regulated pRb and p21.Conclusions.HPV‐positive tonsil SCCs have distinct molecular pathways. Their association with younger patient age suggests that they are biologically distinct from HPV‐negative tumors. © 2004 Wiley Periodicals, Inc. Head and Neck 26: 1–9, 2004
Enhancing the outcome of free latissimus dorsi muscle flap reconstruction of scalp defects
Authors: Lipa Joan E. , Butler Charles E. 
Published: January 2004

AbstractBackground. Reconstruction of scalp and calvarial defects after tumor ablation frequently requires prosthetic cranioplasty and cutaneous coverage. Furthermore, patients often have advanced disease and receive perioperative radiotherapy. We evaluated the complications of scalp reconstruction with a free latissimus dorsi muscle flap in this setting.Methods. The complications and the oncologic and aesthetic outcomes of six consecutive scalp reconstructions with a free latissimus dorsi muscle flap and skin graft in five patients with advanced cancer were retrospectively evaluated. Patient, tumor, defect, reconstructive, and other treatment characteristics were reviewed. Reconstructive and perioperative techniques intended to improve flap survival and aesthetic outcome and reduce complications in these patients.Results. All patients (52–76 years old) had recurrent tumors (sarcoma, melanoma, or squamous cell carcinoma) and received postoperative radiotherapy. The mean scalp defect size was 367 cm2, and partial‐thickness or full‐thickness calvarial resection was required in all six cases. No vein grafts were needed. The mean follow‐up period and disease‐free survival time were 18 and 13 months, respectively. Three patients died of their disease, and two survived disease free. There were no flap failures or dehiscences. Complications consisted of donor site seroma in two patients; partial skin graft loss in one patient; and radiation burns to the flap, face, and ears in one patient. Scalp contour and aesthetic outcome were very good in all cases except for the one case with radiation burns.Conclusions. Good outcomes were achieved using a free latissimus dorsi muscle flap with a skin graft for flap reconstruction in elderly patients with advanced recurrent cancers who received perioperative radiotherapy. Several technical aspects of the reconstruction technique intended to enhance the functional and aesthetic outcome and/or reduce complications were believed to have contributed to the good results. © 2004 Wiley Periodicals, Inc. Head Neck 26: 46–53, 2004