bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shape transformation and cytoskeletal reorganization in activated non‐mammalian thrombocytes
Authors: Lee Kyeng‐Gea , Miller Todd , Anastassov Ivan , Cohen D. William 
Published: March 2004

AbstractThe nucleated thrombocytes of non‐mammalian vertebrates are partially flattened, ovoid cells morphologically distinct from mammalian platelets, and the extent of their functional equivalence is unknown. To test whether they resemble platelets in having similar F‐actin‐based post‐activation stages, rapid fixation/extraction/labeling methods were developed to reveal cytoskeletal organization in dogfish thrombocytes by confocal microscopy. Unactivated cells contained cortical F‐actin plus denser F‐actin co‐localizing with outer marginal band (MB) microtubules. In the post‐activation sequence, determined for the first time by continuous observation of individual thrombocytes following thrombin perfusion, cells rounded and blebbed, spread, and eventually flattened extensively. The MB twisted and then became disorganized, with microtubule bundles remaining centrally located and associated with nuclear clefts. In contrast, F‐actin occupied blebs and outward‐spreading cytoplasm, initially in spiky projections, then predominantly in stress fibers, and inhibitors of F‐actin assembly or myosin ATPase blocked shape changes. Thus, the post‐activation stages and cytoskeletal events observed in nucleated thrombocytes were found to parallel those of platelets.
Effects of ascorbic acid and ascorbic acid 2‐phosphate, a long‐acting vitamin C derivative, on the proliferation and differentiation of human osteoblast‐like cells
Authors: Takamizawa Shinji , Maehata Yojiro , Imai Katsuyuki , Senoo Haruki , Sato Sadao , Hata Ryu‐Ichiro 
Published: March 2004

AbstractIn order to investigate the effect of ascorbic acid (AsA) and ascorbic acid 2‐phosphate (Asc 2‐P), a long‐acting vitamin C derivative, on the growth and differentiation of human osteoblast‐like cells, we supplemented the culture medium of MG‐63 cells with various concentrations (0.25 to 1 mM) of these factors. Asc 2‐P significantly stimulated nascent cell growth at all concentrations in the presence of fetal bovine serum (FBS). On the other hand, AsA showed a growth repressive effect depending on its concentration, and that of FBS. Asc 2‐P also increased expression of osteoblast differentiation markers, such as collagen synthesis and alkaline phosphatase (ALP) activity. These stimulative activities of Asc 2‐P were attenuated by inhibitors of collagen synthesis, indicating that these effects were dependent on collagen synthesis. Electron micrographs of the cells showed the formation of a three‐dimensional tissue‐like structure endowed with a mature extracellular matrix in the presence of Asc 2‐P.
Quality of life in chronic pain is more associated with beliefs about pain, than with pain intensity
Authors: Lamé Inge E. , Peters Madelon L. , Vlaeyen Johan W.S. , Kleef Maarten V. , Patijn Jacob 
Published: March 2004

AbstractObjectives. The objectives of this study were to investigate pain cognitions and quality of life of chronic pain patients referred to a multi‐disciplinary university pain management clinic and to search for predictors of quality of life.Methods. A heterogeneous group of 1208 chronic pain patients referred to the Maastricht university hospital pain clinic participated in this cross‐sectional study. At the initial assessment, all patients completed a set of questionnaires on demographic variables, cause, location, pain intensity (McGill pain questionnaire, MPQ), pain coping and beliefs (pain coping and cognition list, PCCL), pain catastrophising (pain catastrophising scale, PCS) and eight dimensions of quality of life (Rand‐36).Results. The results showed that the present sample of heterogeneous pain patients reported low quality of life on each domain and significantly lower scores than has been found in previous studies with other Dutch chronic pain populations. Patients with low back pain and multiple pain localisations experienced most functional limitations. Women reported more pain, more catastrophising thoughts about pain, more disability and lower vitality and general health. When tested in a multiple regression analysis, pain catastrophising turned out to be the single most important predictor of quality of life. Especially social functioning, vitality, mental health and general health are significantly associated with pain catastrophising.Conclusions. Patients from a multi‐disciplinary university pain clinic experience strikingly low quality of life, whereby low back pain patients and patients with multiple pain localisations have the lowest quality of life. Pain catastrophising showed the strongest association with quality of life, and stronger than pain intensity.
Facilitation and inhibition of withdrawal reflexes following repetitive stimulation: electro‐ and psychophysiological evidence for activation of noxious inhibitory controls in humans
Authors: Bajaj Prem , Arendt‐Nielsen Lars , Andersen Ole K. 
Published: March 2004

AbstractA systematic evaluation of nociceptive withdrawal reflexes and pain rating was undertaken in order to explore the mechanisms underlying temporal summation of repetitive electrocutaneous stimulation in healthy individuals (n=12; age=27.5 ± 1.5 years). Five‐second subreflex threshold (RT) electrocutaneous stimulation at different frequencies (single stimulus, 5, 10, and 20 Hz) and intensities (0.6RT and 0.8RT) was applied on the dorsum of the foot, and the withdrawal reflex from the ipsilateral biceps femoris muscle was measured. The subjects scored the pain intensity on a visual analogue scale (0–100 mm) for the beginning, the middle and the end phase of the 5 s series of stimulation, and the respective averaged reflex size was calculated. The reflex size increased at stimulus frequencies 10 Hz × 0.8RT and 20 Hz × 0.8RT as compared with 5 Hz × 0.8RT (SNK, P<0.05), and by an increase in current intensity from 0.6RT to 0.8RT (SNK, P<0.05). Pain intensity increased with the increase in the current intensity from 0.6RT to 0.8RT (SNK, P<0.05). Profound activation of inhibition following electrocutaneous pain stimuli was demonstrated by reduction in pain intensity and reflex size during the last second as compared with the first second at 0.6RT current intensity (SNK, P<0.05). The pain intensity peaked between 5 and 10 Hz (P<0.05) and was reduced at 20 Hz for current intensities at 0.8RT (P<0.05). This study provides evidence for both frequency dependent central integration of the repetitive electrocutaneous stimuli and activation of a pain inhibitory system by psychophysical and electrophysiological means, demonstrating the delicate balance between neuronal facilitation and inhibition in the human pain system.
Long term therapy of generalized anxiety disorder
Authors: Rouillon Frédéric 
Published: March 2004

AbstractGeneralized anxiety disorder (GAD) is a common (lifetime prevalence: 5.1%), recurrent condition, which often heralds other psychiatric disorders, notably depression. As by definition it is a disorder progressing over months, treatment should be designed on a long term basis. And yet, few studies have been conducted beyond the classical 6–8 weeks characterizing the acute treatment phase. This is especially true of anxiolytics, but also of antidepressants, with the exception of paroxetine and venlafaxine, which are the only drugs approved in this indication in Western countries. The efficacy of psychotherapy, notably relaxation and cognitive-behavioral therapy, is established in the treatment of GAD, but its preferred indications and possible combination with antidepressants are still to be specified. Long term, not to say very long term studies of GAD, as well as depression, will still be required in the future to improve its management and specify therapeutic modalities (combination treatment, optimal duration, continuous or intermittent therapy, choice of psychotherapeutic techniques or agents, …). Early and adequately prolonged treatment should not only result in more numerous remission periods, but also in decreased frequency of co-morbidities whether depressive, addictive, or of another nature, and should also reduce the social impact of GAD.
Chondrocyte apoptosis induced by hydrogen peroxide requires caspase activation but not mitochondrial pore transition
Authors: Lo Marvin Y. , Kim Hubert T. 
Published: March 2004

AbstractThe primary objective of this study was to test the hypothesis that inhibition of mitochondrial permeability transition and/or inhibition of caspase family enzymes can block chondrocyte apoptosis induced by H2O2. Primary human chondrocytes were isolated from normal cartilage by enzymatic digestion. Apoptosis was induced by exposure to H2O2. Chondrocyte apoptosis was quantified using an ELISA for nucleosome formation. Independent confirmation of apoptosis was obtained by TUNEL analysis. H2O2 induced apoptosis in primary human chondrocytes in a time and dose dependent manner. The effects of candidate apoptosis inhibitors were then tested. Chondrocytes were pre‐treated with inhibitors of mitochondrial permeability transition, or one of three different caspase inhibitors, and then incubated with H2O2. Apoptosis was then measured after 16 h of exposure to H2O2. Pre‐treatment with inhibitors of mitochondrial permeability transition did not block apoptosis induced by H2O2. A non‐selective caspase inhibitor, a caspase 3‐selective inhibitor, and a caspase 1‐selective inhibitor, all blocked chondrocyte apoptosis induced by H2O2. These results show that H2O2 triggers chondrocyte apoptosis through caspase activation, independent of mitochondrial membrane permeability transition. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
Crosslinking density influences the morphology of chondrocytes photoencapsulated in PEG hydrogels during the application of compressive strain
Authors: Bryant Stephanie J. , Anseth Kristi S. , Lee David A. , Bader Dan L. 
Published: March 2004

AbstractChondrocyte deformation, which occurs during mechanical loading, is thought to play an important role in the mechano‐transduction pathway. In designing a scaffold that can be gelled in situ for cartilage tissue engineering, an important consideration is the influence of mechanical loading. This study tested the hypothesis that changes in the crosslinking density of a hydrogel scaffold influence the morphology of encapsulated chondrocytes in response to an applied load. Chondrocytes were entrapped in photo‐crosslinkable hydrogel scaffolds based on poly(ethylene glycol) (PEG) with two crosslinking densities, 0.119 and 0.376 mol/l, with the higher density having a 11‐fold higher compressive modulus. The cell‐embedded hydrogels were subjected to static compressive strains between 0% and 20% after 1 and 6 days of culture. Using confocal laser scanning microscopy, chondrocytes in the highly crosslinked gel at day 1 deformed more than gels in the more loosely crosslinked gel. By day 6, this finding was reversed. When single cells within a region were followed, heterogeneities in cell deformation were observed on both a macroscopic and microscopic scale. These heterogeneities were greater in the highly crosslinked gel. These findings demonstrate that different levels of cell deformation and heterogeneity may be obtained by varying the crosslinking density in PEG hydrogels. © 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.
An investigation of stress and pain perception during manual therapy in asymptomatic subjects
Authors: Vicenzino Bill , Cartwright Tim , Collins David , Wright Anthony 
Published: March 2004

Stress perceived by the patient during the application of a manual therapy treatment technique may account for the reported findings of sympathoexcitation and hypoalgesia immediately after its application. This study investigated whether there was a difference in the level of perceived stress and pain before, during and after the application of a treatment condition (treatment, placebo or control technique), or whether the difference related to the time course of subject involvement in the study.Twenty‐four asymptomatic subjects participated in a double‐blind, placebo‐controlled, within‐subjects study in which stress was measured with a stress rating scale and a stress visual analogue scale. Pain experienced by the subject during the application of the treatment technique was measured with a visual analogue scale and modified McGill pain questionnaire. There was no effect of the treatment condition on perceived stress, but there was a reduction in stress levels over the time course of involvement in the experiment, as demonstrated by pre‐application levels of stress. Pain was not produced by the treatment technique.This study demonstrated that stress and pain were not features of the lateral glide manipulation of the cervical spine in asymptomatic subjects. If the dorsal periaqueductal grey region is responsible for the initial effects of manual therapy, as has been previously suggested, then stress and pain do not appear to play a role in activating this system during the application of a manual therapy treatment technique in asymptomatic subjects.
Elevated plasma levels of neuropeptide Y in female fibromyalgia patients
Authors: Anderberg Ulla Maria , Liu Zhurong , Berglund Lars , Nyberg Fred 
Published: March 2004

Neuropeptide Y(NPY) co‐exists with norepinephrine in the sympathetic nervous system, and NPY may represent the sympathetic‐neuronal output. Fibromyalgia syndrome (FMS) patients have perturbations in the hypothalmic‐pituitary‐adrenal (HPA) axis and in the sympathetic stress axis as well. As opioid peptides, monoamines and sex steroids are integrated in the regulation of stress, it is interesting to further explore the role of NPY in FMS patients, as they show many symptoms that are related to perturbations of those systems.In this study, plasma NPY levels were assessed in subgroups of FMS patients: cyclic (regular menstrual cycles), non‐cyclic (post‐menopausal), depressed and non‐depressed patients. In order to examine whether pain and other symptoms seen in FMS patients are correlated to the NPY levels, the patients were also registering 15 different symptoms daily during 28 days. Sex and age‐matched healthy controls were recruited for comparisons. Non‐parametric tests were used for the statistical analyses.The results showed that the NPY levels were significantly elevated in the patients compared to the controls. In the luteal phase of the cyclic patients, the levels of the peptide were higher than in the corresponding controls. For the non‐cyclic patients, there was a positive correlation between physical symptoms and NPY levels, however, pain per se did not reach the significant level of correlation. The non‐depressed patients had the same levels of NPY as the depressed FMS patients, who also had a positive correlation between anxiety and NPY levels.These results suggest that FMS patients have an altered activity in the NPY system, most likely due to prolonged and/or repeated stress, and that the hormonal state and time of the menstrual cycle also may be of importance in the complex pathophysiologic mechanism behind the development of FMS.
Quantification and immunocytochemical characteristics of trigeminal ganglion neurons projecting to the cornea: Effect of corneal wounding
Authors: De Felipe Carmen , Gonzalez Gertrudis G. , Gallar Juana , Belmonte Carlos 
Published: March 2004

The number and immunocytochemical characteristics of trigeminal ganglion neurons providing sensory innervation to the cornea were studied in the mouse. Corneal neurons were retrogradely labelled with fluorogold placed on the cornea after removal of the epithelium with n‐heptanol. Corneal neurons were counted, sized and characterized immunocytochemically with antisera against substance P (SP), calcitonin gene‐related peptide (CGRP), calbindin, calretinin, and with a monoclonal antibody (RT97) against neurofilament proteins. A total of 258 corneal neurons were counted, most of them located in the ophthalmic division of the trigeminal ganglion. They represent only a small fraction (1.3%) of the population of trigeminal ganglion neurons. More than 70% of corneal neurons were classified as ‘small dark’ according to their cell body area and the absence of immunoreactivity to RT97. A low percentage of corneal neurons, usually large in size, contained calcium binding proteins. Fifty‐eight percent of the corneal neurons were immunoreactive to CGRP, and 20% to SP Corneal wounding with NaOH, which affects stromal nerve trunk, did not modify the total number of corneal neurons or their neuropeptide content. However, this increased the total number of calbindin‐positive and decreased the RT97‐positive neurons. Thus, unlike in other nociceptive neurons, peripheral axotomy did not modify the SP/CGRP content of corneal neurons.Trigeminal ganglion neurons projecting to the cornea are similar in size and neuropeptide content to nociceptive neurons of other territories. Their number is high in relation to the corneal surface, thus confirming that the cornea has a large nociceptive representation in the trigeminal ganglion.
Study calls for improvements to U.S. visa process for students, scholars
Authors: Showstack Randy 
Published: March 2004

U.S. federal agencies are implementing some measures to reduce delays in providing foreign scientists and students with non‐immigrant visas, although additional steps could help to improve the cumbersome process, according to a government study released on 25 February by the U.S. General Accounting Office (GAO).The study, which was requested by the House of Representatives Science Committee, reviewed the issuance of F‐l and J‐1 visas in light of national security measures put in place after September 11, 2001. The committee has expressed concerns about whether new security measures are detrimental to scientific research by unnecessarily delaying the issuance of visas to foreign students and scholars.
Effects of GW274150, a novel and selective inhibitor of iNOS activity, in acute lung inflammation
Authors: Dugo Laura , Marzocco Stefania , Mazzon Emanuela , Paola Rosanna Di , Genovese Tiziana , Caputi Achille P , Cuzzocrea Salvatore 
Published: March 2004

The aim of this study was to investigate the effect of GW274150, a novel, potent and selective inhibitor of inducible nitric oxide synthase (iNOS) activity in a model of lung injury induced by carrageenan administration in the rats.
Injection of carrageenan into the pleural cavity of rats elicited an acute inflammatory response characterized by: fluid accumulation in the pleural cavity which contained a large number of polymorphonuclear cells (PMNs) as well as an infiltration of PMNs in lung tissues and subsequent lipid peroxidation, and increased production of nitrite/nitrate (NOx), tumour necrosis factor α (TNF‐α) and interleukin‐1β (IL‐1β).
All parameters of inflammation were attenuated in a dose‐dependent manner by GW274150 (2.5, 5 and 10 mg kg−1 injected i.p. 5 min before carrageenan).
Carrageenan induced an upregulation of the intracellular adhesion molecules‐1 (ICAM‐1), as well as nitrotyrosine and poly (ADP‐ribose) (PAR) as determined by immunohistochemical analysis of lung tissues.
The degree of staining for the ICAM‐1, nitrotyrosine and PAR was reduced by GW274150. These results clearly confirm that NO from iNOS plays a role in the development of the inflammatory response by altering key components of the inflammatory cascade.
GW274150 may offer a novel therapeutic approach for the management of various inflammatory diseases where NO and related radicals have been postulated to play a role.

British Journal of Pharmacology (2004) 141, 979–987. doi:10.1038/sj.bjp.0705683
Carbamoylating chemoresistance induced by cobalt pretreatment in C6 glioma cells: putative roles of hypoxia‐inducible factor‐1
Authors: Yang Ding‐I , Chen Shang‐Der , Yang Ya‐Ting , Ju Tzyh‐Chwen , Xu Jin‐Ming , Hsu Chung Y 
Published: March 2004

We tested whether pretreatment of reagents known to induce hypoxia‐inducible factor‐1 (HIF‐1) may confer chemoresistance against cytotoxicity of 1,3‐bis(2‐chloroethyl)‐1‐nitrosourea (BCNU) to rat C6 glioma cells. We also studied which cytotoxic mechanism(s) of chloroethylnitrosoureas could be neutralized by cobalt preconditioning.
Preconditioning of rat C6 glioma cells with cobalt chloride (300 μM, 2 h) induced HIF‐1 binding activity based on electrophoretic mobility shift assay (EMSA). Results from Western blotting confirmed a heightened HIF‐1α level upon cobalt chloride exposure (300–400 μM, 2 h). Cobalt chloride (300 μM) pretreatment for 2 h substantially neutralized BCNU toxicity, leading to increases in glioma cell survival based on MTT assay. In addition, pre‐exposure of C6 cells with desferrioxamine (DFO; 400 μM, 3 h), an iron chelator known to activate HIF‐1, also induced HIF‐1 binding and rendered the glioma cells resistant to cytotoxicity of BCNU.
Pre‐incubation with cobalt chloride abolished the cytotoxicity of several carbamoylating agents including 2‐chloroethyl isocyanate and cyclohexyl isocyanate, the respective carbamoylating metabolites of BCNU and 1‐(2‐chloroethyl)‐3‐cyclohexyl‐1‐nitrosourea. The protective effect of cobalt exposure, however, was not observed when cells were challenged with alkylating agents including temozolomide.
Cadmium chloride (50 μM) effectively reversed cobalt‐induced HIF‐1 activation. Correspondingly, cadmium chloride suppressed carbamoylating chemoresistance mediated by cobalt chloride pretreatment. Furthermore, both double‐stranded oligodeoxynucleotide (ODN) decoy with HIF‐1 cognate sequence and antisense phosphorothioate ODNs against HIF‐1α partially abolished the carbamoylating chemoresistance associated with cobalt preconditioning.
Our results suggest that cobalt‐ or DFO‐preconditioning may enhance glioma carbamoylating chemoresistance that is dependent, at least in part, on induction of HIF‐1.

British Journal of Pharmacology (2004) 141, 988–996. doi:10.1038/sj.bjp.0705687
Neuroprotective effects of resveratrol against β‐amyloid‐induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C
Authors: Han Ying‐Shan , Zheng Wen‐Hua , Bastianetto Stéphane , Chabot Jean‐Guy , Quirion Rémi 
Published: March 2004

Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models.
The present study evaluated the neuroprotective effects of resveratrol against amyloid β(Aβ)‐induced toxicity in cultured rat hippocampal cells and examined the role of the protein kinase C (PKC) pathway in this effect.
Pre‐, co‐ and post‐treatment with resveratrol significantly attenuated Aβ‐induced cell death in a concentration‐dependent manner, with a concentration of 25 μM being maximally effective.
Pretreatment (1 h) of hippocampal cells with phorbol‐12‐myristate‐13‐acetate, a PKC activator, at increasing concentrations (1–100 ng ml−1), resulted in a dose‐dependent reduction in Aβ‐induced toxicity, whereas the inactive 4α‐phorbol had no effect.
Pretreatment (30 min) of hippocampal cells with GF 109203X (1 μM), a general PKC inhibitor, significantly attenuated the neuroprotective effect of resveratrol against Aβ‐induced cell death.
Treatment of hippocampal cells with resveratrol (20 μM) also induced the phosphorylation of various isoforms of PKC leading to activation.
Taken together, the present results indicate that PKC is involved in the neuroprotective action of resveratrol against Aβ‐induced toxicity.

British Journal of Pharmacology (2004) 141, 997–1005. doi:10.1038/sj.bjp.0705688