bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of psychiatric disorders in an onset cohort of adults with type 1 diabetes
Authors: Petrak Frank , Hardt Jochen , Wittchen Hans‐Ulrich , Kulzer Bernhard , Hirsch Axel , Hentzelt Frieder , Borck Katrin , Jacobi Frank , Egle Ulrich Tiber , Hoffmann Sven Olaf
Published: June 2003

Background

Previous studies indicate a high prevalence of psychiatric disorders in adults with type 1 diabetes mellitus. The aim of our study was to determine if newly diagnosed adults with type 1 diabetes already have an elevated rate of psychiatric disorders at the beginning of their physical illness.

Methods

The authors consecutively recruited 313 newly diagnosed, adult inpatients with type 1 diabetes (age 17–40 years) from 12 hospitals. A national, representative population sample of 2046 persons of a similar age range served as the reference group. Psychiatric disorders were measured in both groups using structured interviews that provided diagnoses according to DSM‐IV.

Results

There was a point prevalence of 12.5% for psychiatric disorders in the sample. The most frequent conditions were anxiety and affective disorders. Subjects with type 1 diabetes demonstrated a rate of major depressive episodes twice that of the reference group (5.8% vs 2.7%, p < 0.003; corrected for confounders). Apart from this finding, there was no significantly increased prevalence of psychiatric disorders in the diabetes sample as compared to the general German population.

Conclusion

The rate of major depressive episodes in the new onset cohort of type 1 diabetes patients was double that of the population as a whole. However, the hypothesis, that newly diagnosed type 1 diabetes patients have more psychiatric disorders than the general population, was not confirmed. Copyright © 2003 John Wiley & Sons, Ltd.
Spot volume vs. amount of protein loaded onto a gel: A detailed, statistical comparison of two gel electrophoresis systems
Authors: Zhan Xianquan , Desiderio Dominic M.
Published: May 2003

The long‐term goal of this research program is to clarify the molecular mechanisms that participate in the formation of human pituitary macroadenomas. One approach to that goal is to characterize the differentially expressed proteins that are found by a comparison of the proteomes of control pituitary vs. macroadenoma tissues. In order to accurately perform a comparative proteomics study, based on the combination of two‐dimensional polyacrylamide gel electrophoresis (2‐D PAGE) and PDQuest 2‐D analysis software, a reproducible 2‐DE separation system with a wide linear dynamic measure range is needed. A typical horizontal system is the Multiphor II system that analyzes one gel at a time, using a precast gradient gel (180×245×0.5 mm); a typical vertical system is the Dodeca system that analyzes up to 12 gels at a time on a single‐concentration gel (190×205×1.0 mm). We have evaluated (Zhan and Desiderio, Electrophoresis 2003, 24, 1834–1846) the spatial and quantitative reproducibility of the two second‐dimensional gel systems to separate a human pituitary proteome; that study showed a higher reproducibility for the Dodeca gel system. This present study investigated the relationship between the spot volume and the amount of protein loaded onto the gel for those two 2‐D systems. The results demonstrated that the Dodeca gel system provides a wider linear dynamic range to measure the changes in the protein abundance in pituitary proteome.
Anthracycline‐dependent heat‐induced transition from positive to negative supercoiled DNA
Authors: Víglasky Viktor , Valle Francesco , Adamčík Jozef , Joab Irene , Podhradsky Dušan , Dietler Giovanni
Published: May 2003

The conformational stability of individual DNA topoisomers depends on the concentration of DNA intercalating drugs. To study the DNA‐drug interaction, we used ethidium bromide (EtBr) and negative supercoiled pUC19 as a model system. The effects of two anthracyclines widely used in cancer therapy, daunorubicin (Dau) and doxorubicin (Doxo), and EtBr were compared. In spite of their different chemical structures and intercalation mode, all intercalating agents show similar effects on the conformational stability of supercoiled DNA. Our observations show that the studied intercalators have at least two main effects on the supercoiled DNA: (i) they decrease the level of negative supercoiling and, at certain concentrations, they may induce positive supercoiling in DNA; (ii) a temperature increase can cause a recovery of negative supercoiling in DNA. The conformational stability of plasmid DNA‐drug complexes has been investigated by temperature gradient gel electrophoresis (TGGE). We demonstrate the suitability of TGGE for this purpose, because it offers a global view on DNA‐drug complexes over a continuous range of temperature. Images of DNA plasmids adsorbed onto a substrate at different temperatures and drug concentrations were acquired by atomic force microscopy (AFM), allowing us to distinguish directly the conformation chirality assumed by the plasmid under different conditions confirming TGGE results. Our detection system allows to characterize unknown drugs and to determine their intercalating properties.
Differences in the spatial and quantitative reproducibility between two second‐dimensional gel electrophoresis systems
Authors: Zhan Xianquan , Desiderio Dominic M.
Published: May 2003

Two‐dimensional polyacrylamide gel electrophoresis (PAGE), together with 2‐D gel electrophoresis (GE) analysis software, is a common technique to analyze a complex proteome. In order to accurately locate the differentially expressed proteins in human pituitary macroadenoma tissues in our long‐term research program to clarify the molecular mechanisms of macroadenoma formation, a reproducible separation system is needed. An immobilized pH‐gradient dry gel‐strip (IPG strip) has been extensively used for first‐dimensional isoelectric focusing (IEF), and has achieved a high degree of reproducibility in the IEF direction. For the second dimension (SDS‐PAGE), different types of gel systems are available, including horizontal vs. vertical gel systems, and gradient vs. constant‐percentage gels. A typical horizontal system is the Multiphor II system that analyzes one gel at a time, using a precast gradient gel (180×245×0.5  mm), and a typical vertical system is the Dodeca system, which analyzes up to 12 gels at a time, using usually a single‐concentration gel (190×205×1 mm). The present study evaluated the spatial and quantitative reproducibility of the two systems for the separation of the complex human pituitary proteome. PDQuest software was used to analyze the digitized gel‐image data, and SPSS statistical software was used to analyze the data. The results demonstrated a high percentage (>99%) of protein‐spot matches within each electrophoretic system. The Dodeca gel system demonstrated better between‐gel reproducibility for spot position, higher resolution in the Sodium dodecyl sulfate (SDS)‐PAGE direction, lower gel background, better spot quality, and higher reproducibility of the spot volume.
Profiling stage‐dependent changes of protein expression in Caenorhabditis elegans by mass spectrometric proteome analysis leads to the identification of stage‐specific marker proteins
Authors: Mádi András , Mikkat Stefan , Ringel Bruno , Thiesen Hans‐Jürgen , Glocker Michael O.
Published: May 2003

Proteome maps obtained by synchronization of the wild‐type Caenorhabditis elegans development reflected stage‐dependent molecular differences and revealed dynamic cytoskeletal processes during ontogenesis. Distinct protein spots that may function as molecular markers for the corresponding developmental stages were mass spectrometrically identified. The amount of the Cu2+– Zn2+ superoxide dismutase (CE23550) and an aspartyl proteinase (CE21681) was highest in the first larval stage (L1) and decreased during the ontogenesis from the first larval stage to the adult. Tropomyosin III (CE29059) was prominently present in the first and second larval stage (L1/L2). Abundances of actin 1 or 4 (CE12358 or CE13148) and tropomyosin I (CE28782) were particularly high in multiple spots in the third larval stage (L3). Interestingly, the amount of DIM‐1 protein (CE27706), reflected by two spots, was the lowest in this stage. A particular splicing factor (CE31089) was detected only in the fourth larval stage (L4), whereas a spot with high abundance representing the cuticle collagen (CE02272) was only found highly expressed in adult animals (A). In addition, a Ca2+‐binding protein (CE12368) and one protein spot which has not yet been identified, both reached their maximal spot intensities in the adult stage (A). Moreover, the ASP‐1, CCT‐5, GPD‐1, GPD‐2, HSP‐6, HSP‐16.2, IFB‐2, LEC‐2, LIN‐53, LMN‐1, MDH‐1, NUD‐1, RPA‐0, RSP‐12, SOD‐1, TBB‐1, TBB‐2, TMY‐1, UNC‐60, and VIT‐2 proteins for which mutants are available and two still unidentified protein spots which were present in all developmental stages, have been reproducibly localized in proteome maps of distinct ontogenesis states.
Vertical agarose gel electrophoresis and electroblotting of high‐molecular‐weight proteins
Authors: Warren Chad M. , Krzesinski Paul R. , Greaser Marion L.
Published: May 2003

The electrophoretic separation of high‐molecular‐weight proteins (> 500 kDa) using polyacrylamide is difficult because gels with a large enough pore size for adequate protein mobility are mechanically unstable. A 1% vertical sodium dodecyl sulfate (SDS)‐agarose gel electrophoresis (VAGE) system has been developed that allows titin (a protein with the largest known SDS subunit size of 3000–4000 kDa) to migrate over 10 cm in a ∼13 cm resolving gel. Such migration gives clear and reproducible separation of titin isoforms. Proteins ranging in size from myosin heavy chain (∼ 220 kDa) up to titin can be resolved on this gel system. Electroblotting of these very large proteins was nearly 100% efficient. This VAGE system has revealed two titin size variants in rabbit psoas muscle, two N2BA bands in rabbit cardiac muscle, and species differences between titins from rat and rabbit muscle. Agarose electrophoresis should be the method of choice for separation and blotting of proteins with very large subunit sizes.
Proteomic profiling of pancreatic ductal carcinoma cell lines treated with trichostatin‐A
Authors: Cecconi Daniela , Scarpa Aldo , Donadelli Massimo , Palmieri Marta , Hamdan Mahmoud , Astner Hubert , Righetti Pier Giorgio
Published: May 2003

A pancreatic adenocarcinoma cell line (Paca44) was treated with trichostatin‐A (TSA), a potent inhibitor of histone deacetylases, in order to evaluate the effect of this drug on protein expression. Master maps of control and treated Paca44 cells were generated by analysis with the PDQuest software. The comparison between such maps showed up‐ and downregulation of 51 polypeptide chains, out of a total of 700 spots detected by a medium‐sensitivity stain, micellar Coomassie Brilliant Blue. Fingerprinting by matrix‐assisted laser desorption/ionization‐time of flight (MALDI‐TOF)‐mass spectrometry analysis enabled the identification of 22 of these spots. Among these proteins, of particular interest are the two downregulated proteins nucleophosmin and translationally controlled tumor protein, as well as the upregulated proteins programmed cell death protein 5 (also designated as TFAR19) and stathmin (oncoprotein 18). The modulation of these four proteins is consistent with our observation that TSA is able to inhibit cell growth of Paca44 by causing cell cycle arrest at the G2 phase and apoptotic cell death.
Testing the mixture‐of‐distributions hypothesis using “realized” volatility
Authors: Luu James C. , Martens Martin
Published: May 2003

The mixture‐of‐distributions hypothesis (MDH) posits that price volatility and
trading volume are both subordinated to the same information arrival rate or “news” process.
Existing studies that test MDH have the problem that both the information arrival rate and volatility are
unobservable. Recent work (e.g., Andersen et al., 2001) suggests that
intraday returns can be used to construct estimates of daily return volatility that are more precise than those
constructed using daily returns. In a way, realized volatility becomes observable. Conducting a number of tests
of MDH we find that every conclusion based on the daily squared return is reversed when using realized
volatility based on intraday returns. Hence, the mixed evidence on MDH in the existing literature can in part be
attributed to the use of poor realized volatility measures. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark
23:661–679, 2003
The interrelation of price volatility and trading volume of currency options
Authors: Sarwar Ghulam
Published: May 2003

This article examines the interrelations between future volatility of the U.S. dollar/British pound
exchange rate and trading volume of currency options for the British pound. The future volatility of the
exchange rate is approximated alternatively by implied volatility and by IGARCH volatility. The results suggest
the presence of strong contemporaneous positive feedbacks between the exchange rate volatility and the trading
volume of call and put options. Previous option volumes have significant predictive power with respect to the
expected future volatility of the dollar/pound exchange rate. Similarly, lagged volatilities jointly have
significant predictive power for option volume. Although option volume (volatility) responds somewhat
differently to individual volatility (volume) terms under the two volatility measures, the overall
volume‐volatility relations are broadly similar between the implied and IGARCH volatilities. The results
generally support the hypothesis that the information‐based trading explains more of the trading volume
in currency options on the U.S. dollar/British pound exchange rate than hedging. © 2003 Wiley
Periodicals, Inc. Jrl Fut Mark 23:681–700, 2003
Decreased price clustering in FTSE100 futures contracts following a transfer from floor to electronic trading
Authors: ap Gwilym Owain , Alibo Evamena
Published: May 2003

The issues of price clustering and electronic trading have triggered important recent debates, and generated
interest from regulators due to their potential implications for market quality, stability, and fairness. This
paper brings together these issues by examining whether price‐clustering behavior differs following a
transfer of futures contracts from open outcry trading to an electronic system. The results are unique in
demonstrating a structural change in price clustering following the move to automated trading, with the level of
price clustering dropping from around 98.5% of prices at even ticks under floor trading to approximately
75% under electronic trading. Such a change in pricing behavior amounts to a reduction in the effective
tick size, and is an important factor in reducing observed bid‐ask spreads. © 2003 Wiley
Periodicals, Inc. Jrl Fut Mark 23:647–659, 2003
Futures market equilibrium under Knightian uncertainty
Authors: Lien Donald , Wang Yaqin
Published: May 2003

This paper examines the effects of Knightian uncertainty on a commodity futures market within the
Newbery‐Stiglitz framework. It is shown that Knightian traders act more conservatively. In a partial
trade equilibrium, risk aversion and Knightian uncertainty have qualitatively similar effects on the equilibrium
price and the equilibrium trading volume. Full‐trade and no‐trade equilibria are likely to prevail
when the producer and the speculator incur different Knightian uncertainty. Herein different impacts of risk
aversion and Knightian uncertainty are observed. © 2003 Wiley Periodicals, Inc. Jrl Fut Mark
23:701–718, 2003
Stock return dynamics, option volume, and the information content of implied volatility
Authors: Mayhew Stewart , Stivers Chris
Published: May 2003

This article reports new empirical results on the information content of implied volatility, with respect to
modeling and forecasting the volatility of individual firm returns. The 50 firms with the highest option volume
on the Chicago Board Options Exchange between 1988 and 1995 are examined. First, the results indicate that the
ability of implied volatility to subsume all relevant information about conditional variance depends on option
trading volume. For the most active options in the sample, implied volatility reliably outperforms GARCH and
subsumes all information in return shocks beyond the first lag. For these active options, implied volatility
performs substantially better than indicated by the prior results of Lamoureux and Lastrapes (1993), despite significant methodological improvements in the time‐series
volatility models in this study including the use of high‐frequency intraday return shocks. For the lower
option‐volume firms in the sample, the performance of implied volatility deteriorates relative to
time‐series volatility models. Finally, compared to a time‐series approach, the implied volatility
of equity index options provides reliable incremental information about future firm‐level volatility.
© 2003 Wiley Periodicals, Inc. Jrl Fut Mark 23:615–646, 2003
Enhanced binding of nor‐binaltorphimine to κ‐opioid receptors in rats dependent on butorphanol
Authors: Fan Lir‐Wan , Tien Lu‐Tai , Tanaka Sachiko , Sasaki Kenro , Park Younjoo , Ma Tangeng , Rockhold Robin William , Ho Ing Kang
Published: May 2003

Autoradiographic characterization of binding for brain κ1 ([3H]CI‐977) and κ2 ([3H]bremazocine) in the presence of DAMGO ([D‐Ala2,N‐Me‐Phe4,Gly5‐ol]‐enkephalin), DPDPE ([D‐Pen2, D‐Pen5]‐enkephalin), and U‐69,593 opioid receptors, in the presence of different concentrations of a selective unlabeled κ‐opioid receptor antagonist, nor‐binaltorphimine (nor‐BNI), was performed in rats in which dependence on or withdrawal from butorphanol had been established. Dependence was induced by a 72 hr intracerebroventricular (i.c.v.) infusion with butorphanol (26 nmol/μl/hr; butorphanol dependent). Butorphanol withdrawal was produced by terminating the infusion of butorphanol in dependent animals. Responses were studied 7 hr following termination (butorphanol withdrawal). IC50 values from competition studies were estimated by fitting inhibition curves for both κ1‐ and κ2‐opioid receptor assays. In both dependent and withdrawal groups, the IC50 values obtained against [3H]CI‐977 or [3H]bremazocine with nor‐BNI were decreased (ratios of ∼0.03–0.21 and ∼0.05–0.42 vs. control, respectively) in brain regions, including frontal cortex, nucleus accumbens, claustrum, dorsal endopiriform nucleus, caudate putamen, parietal cortex, posterior basolateral amygdaloid nucleus, dorsomedial hypothalamus, hippocampus, posterior paraventricular thalamic nucleus, periaqueductal gray, substantia nigra, superficial gray layer of the superior colliculus, ventral tegmental area, and locus coeruleus, compared with control. These results indicate that, in butorphanol‐dependent and butorphanol‐withdrawal rats, the brain κ1‐ and κ2‐opioid receptors developed a supersensitivity to antagonist binding. © 2003 Wiley‐Liss, Inc.
Molecular mechanisms of glutamate neurotoxicity in mixed cultures of NT2‐derived neurons and astrocytes: Protective effects of coenzyme Q10
Authors: Sandhu Jagdeep K. , Pandey Siyaram , Ribecco‐Lutkiewicz Maria , Monette Robert , Borowy‐Borowski Henryk , Walker P. Roy , Sikorska Marianna
Published: May 2003

Although glutamate excitotoxicity has long been implicated in neuronal cell death associated with a variety of neurological disorders, the molecular mechanisms underlying this process are not yet fully understood. In part, this is due to the lack of relevant experimental cell systems recapitulating the in vivo neuronal environment, mainly neuronal–glial interactions. To explore these mechanisms, we have analyzed the cytotoxic effects of glutamate on mixed cultures of NT2/N neurons and NT2/A astrocytes derived from human NT2/D1 cells. In these cultures, the neurons were resistant to glutamate alone (up to 2 mM for 24–48 hr), but they responded to a simultaneous exposure to 0.5 mM glutamate and 6 hr of hypoxia. Neuronal cell death occurred during subsequent periods of reoxygenation (>30% within 24 hr). This was associated with a marked decrease of intracellular ATP, a significant increase in reactive oxygen species (ROS) and downregulation of glutamate uptake by astrocytes. Thus, under energy failure and high levels of ROS production, only the neurons from these mixed cultures succumbed to glutamate neurotoxicity; the astrocytic cells remained unaffected by the treatment. Taken together, our data suggested that glutamate excitotoxicity might be due to the energy failure and oxidative stress affecting the properties of the NMDA glutamate receptors and causing impairment of glutamate transporters. Cells pretreated for 72 hr with 10 μg/ml of coenzyme Q10 (functions both as a ROS scavenger and co‐factor of mitochondrial electron transport), were protected, suggesting a useful role for coenzyme Q10 in treatments of neurological diseases associated with glutamate excitotoxicity. A model of the complex interactions between neurons and astrocytes in regulating glutamate metabolism is presented. © 2003 Government of Canada. Exclusive worldwide publication rights in the article have been transferred to Wiley‐Liss, Inc.
Testosterone up‐regulates aquaporin‐4 expression in cultured astrocytes
Authors: Gu Feng , Hata Ryuji , Toku Kazuko , Yang Lihua , Ma Yong‐Jie , Maeda Nobuji , Sakanaka Masahiro , Tanaka Junya
Published: May 2003

Aquaporin‐4 (AQP4) is located on astrocyte endfeet that face blood vessels in the brain and in the pia. It is thought to play a crucial role in the development of brain edema. To confirm the notion that sex steroids and dexamethasone influence brain edema through AQP4 regulation, we investigated the effects of 17β‐estradiol, testosterone, and dexamethasone on the expression of AQP4 in cultured astrocytes. Testosterone significantly up‐regulated AQP4 at the level of both protein and mRNA. At a concentration of 100 nM, testosterone significantly increased AQP4 protein levels and ameliorated the osmotic fragility of astrocytes from hypoosmotic stress, suggesting that the increased levels of AQP4 facilitated the testosterone function. Moreover, this effect was attenuated by the protein kinase C activator 12‐O‐tetradecanoylphorbol 13‐acetate, which can rapidly decrease AQP4 mRNA expression, indicating that the response was specific. These results indicate that AQP4 can alter the osmotic fragility of astrocytes and that testosterone can influence brain edema through AQP4 regulation, whereas 17β‐estradiol and dexamethasone cannot. © 2003 Wiley‐Liss, Inc.
Effects of peroxisome proliferator‐activated receptor γ ligands ciglitazone and 15‐deoxy‐Δ12,14‐prostaglandin J2 on rat cultured cerebellar granule neuronal viability
Authors: Smith Steven A. , Monteith Gregory R. , Holman Nicola A. , Robinson Jodie A. , May Fiona J. , Roberts‐Thomson Sarah J.
Published: May 2003

Peroxisome proliferator‐activated receptor γ (PPARγ) has been the focus of studies assessing its potential neuroprotective role. These studies have shown either neuroprotection or neurotoxicity by PPARγ ligands. Comparison of these studies is complicated by the use of different PPARγ ligands, mechanisms of neurotoxicity induction, and neuronal cell type. In this study, we compared the effects of the synthetic PPARγ ligand ciglitazone with an endogenous PPARγ ligand, 15‐deoxy‐Δ12,14‐prostaglandin J2 (15‐deoxy PGJ2), on inherent neurotoxicity and neuroprotection using a reduction in extracellular KCl in rat cultured cerebellar granule neurons (CGN). We also assessed the effects of these ligands on c‐Jun protein expression, which is up‐regulated on induction of low‐KCl‐mediated neuronal apoptosis as well as being associated with PPAR in other cell types. We showed that PPARγ mRNA is expressed in CGN cultures and observed ciglitazone‐ and 15‐deoxy PGJ2‐mediated inherent neurotoxicity that was concentration and time dependent. c‐Jun was only modestly increased in the presence of ciglitazone but was markedly up‐regulated by 15‐deoxy PGJ2 after 12 hr. Treatment of CGN cultures with ciglitazone simultaneous with KCl withdrawal resulted in a modest, time‐dependent neuroprotection. Such neuroprotection after KCl withdrawal was not observed with 15‐deoxy PGJ2. Despite the absence of neuroprotection, 15‐deoxy PGJ2 markedly inhibited the early up‐regulation of c‐Jun during KCl withdrawal. These studies suggest that ciglitazone and 15‐deoxy PGJ2 have markedly different effects on inherent and low‐KCl‐induced toxicity and c‐Jun expression in CGN, indicating potential non‐PPARγ mechanisms. © 2003 Wiley‐Liss, Inc.
Transplantation of human adult astrocytes: Efficiency and safety requirements for an autologous gene therapy
Authors: Ridet Jean‐Luc , Sarkis Chamsy , Serguera Che , Zennou Véronique , Charneau Pierre , Mallet Jacques
Published: May 2003

Ex vivo gene therapy is emerging as a promising approach for the treatment of neurodegenerative diseases and central nervous system (CNS) trauma. We have shown previously that human adult astrocytes can be expanded in vitro and can express various therapeutic transgenes (Ridet et al. [1999] Hum. Gene Ther. 10:271–280; Serguera et al. [ 2001] Mol. Ther. 3:875–881). Here, we grafted normal and lentivirally‐modified human adult astrocytes into the striatum and spinal cord of nude mice to test whether they are suitable candidates for ex vivo CNS gene therapy. Transplanted cells survived for at least 2 months (longest time analyzed) and sustained transgene expression. Importantly, the absence of proliferating cell nuclear antigen (PCNA) staining, a hallmark of cell division, ascertains the safety of these cells. Thus, adult human astrocytes are a promising tool for human CNS repair; they may make autologous ex vivo gene transfer feasible, thereby avoiding the problems of immunological rejection and the side effects of immunosuppressors. © 2003 Wiley‐Liss, Inc.
Lymphocyte infiltration in the injured brain: Role of proinflammatory cytokines
Authors: Raivich Gennadij , Bohatschek Marion , Werner Alexander , Jones Leonard L. , Galiano Matthias , Kloss Christian U.A. , Zhu Xing‐Zu , Pfeffer Klaus , Liu Zhi Qiang
Published: May 2003

Studies using mouse axotomised facial motoneuron model show a strong and highly selective entry of CD3+ lymphocytes into the affected nucleus, with a maximum at Day 14, which coincides with the peak of neuronal cell death, microglial phagocytosis, and increased synthesis of interleukin‐1 beta (IL1β), tumour necrosis factor‐alpha (TNFα) and interferon‐gamma (IFNγ). We explored the possible involvement of these cytokines during the main phase of lymphocyte recruitment into the axotomised facial motor nucleus 7–21 days after nerve cut using mice homozygously deficient for IL1 receptor type 1 (IL1R1−/−), TNF receptor type 1 (TNFR1−/−), type 2 (TNFR2−/−) and type 1 and 2 (TNFR1&2−/−), IFNγ receptor type 1 (IFNγR1−/−), and the appropriate controls for the genetic background. Transgenic deletion of IL1R1 led to a 54% decrease and that of TNFR2 to a 44% reduction in the number of CD3+ T‐cells in the axotomised facial motor nucleus, with a similar relative decrease at Day 7, 14, and 21. Deletion of TNFR1 or IFNγR1 had no significant effect. Deletion of both TNFR1 and 2 (TNFR1&2−/−) caused a somewhat stronger, 63% decrease than did TNFR2 deletion alone, but this could be due to an almost complete inhibition of neuronal cell death. No mutations seemed to inhibit aggregation of CD3+ T‐cells around glial nodules consisting of Ca‐ion binding adaptor protein‐1 (IBA1)+ phagocytotic microglia and neuronal debris. Altogether, the current data show the importance of IL1R1 and TNFR2 as the key players during the main phase of lymphocyte recruitment to the damaged part of the central nervous system. © 2003 Wiley‐Liss, Inc.
Effect of tranexamic acid incorporated in fibrin sealant clots on the cell behavior of neuronal and nonneuronal cells
Authors: Cox S. , Cole M. , Mankarious S. , Tawil N.
Published: May 2003

Fibrin sealants are commonly used for hemostasis following surgery on various types of tissues. Aprotinin, an effective fibrinolysis inhibitor, is one of the components in some fibrin sealant products currently available. Tranexamic acid (tAMCHA) is another fibrinolysis inhibitor and is used as an alternative to aprotinin. Recent studies on fibrin sealant products containing tAMCHA indicate that it may be responsible for various adverse reactions when used in neurological applications. To determine a possible mechanism for such adverse reactions, we examined the effect of tAMCHA on the behavior of neuronal and nonneuronal cells using in vitro assays. The data indicate that different concentrations of tAMCHA incorporated in fibrin clots had no effect on the initial cell adhesion of either proliferative cells (glial cells and fibroblasts) or nonproliferative cells (neuronal cells) to the fibrin clots. Moreover, a high concentration of tAMCHA (300–450 mM) incorporated in the fibrin clots increased glial and fibroblast proliferation on fibrin clots. However, because tAMCHA is known to leach out of the fibrin clots, we have also examined the effect of solubilized tAMCHA in a growth medium on cells seeded on matrix‐coated surfaces. A high concentration (300–450 mM) of tAMCHA detached all cell types from matrix‐coated dishes. Our model suggests that tAMCHA in fibrin clots has no adverse effect on cells bound to the fibrin clots; however, tAMCHA leaching out from the fibrin clots reduces adhesion of adjacent cells bound to their natural extracellular matrix. Thus, a high concentration of tAMCHA should not be used as a fibrinolysis inhibitor in fibrin sealant products, especially in neurosurgery. © 2003 Wiley‐Liss, Inc.
Overexpression of V‐1 prevents nitric oxide‐induced cell death: Involvement of enhanced tetrahydrobiopterin biosynthesis
Authors: Yuyama Kohei , Yamamoto Hideko , Nakamura Kazuhiro , Nishizaki Itone , Yamakuni Tohru , Song Si‐Young , Sora Ichiro , Nagatsu Toshiharu , Yamamoto Toshifumi
Published: May 2003

Previously we reported that the synthesis of catecholamines, dopamine, and noradrenaline was enhanced by overexpression of V‐1 protein, a neuronal protein active in the initial stage of development of the rat cerebellum, in the neuronal cell line PC12D, a model of dopamine cells (Yamakuni et al. [1998] J. Biol. Chem. 273:27051–27054). To investigate the physiological role of this protein, we examined the effect of V‐1 overexpression on cell toxicity induced by nitric oxide (NO) used at low concentrations. Two clones of PC12D cells overexpressing V‐1, transfectants termedV1‐46andV1‐69, were significantly more resistant to NOR3 (an NO donor) but not to etoposide (an inhibitor of topoisomerase II)‐induced apoptotic cell death than the control cells (termedC‐7andC‐9) that had been transfected with the vector alone. The addition of L‐DOPA, dopamine, or noradrenaline to the medium did not abolish NOR3‐induced cell death in PC12D cells. Moreover, pretreatment of V1‐46 and V1‐69 cells with L‐α‐methyl‐p‐tyrosine (α‐MPT), an inhibitor of tyrosine hydroxylase, to inhibit catecholamine biosynthesis did not affect the resistance to NO toxicity. These results indicate that the catecholamine levels increased by V‐1 overexpression did not produce the protection against NOR3‐induced toxicity. We further showed that overexpression of V‐1 enhanced the synthesis of (6R)‐L‐erythro‐5,6,7,8‐tetrahydrobiopterin (BH4). In addition, pretreatment with BH4or with sepiapterin, which is converted to BH4intracellularly, significantly protected PC12D cells in a dose‐dependent manner. The increased BH4synthesis by V‐1 overexpression was dose dependently inhibited by pretreatment with diaminohydroxypyrimidine (DAHP), an inhibitor of GTP‐cyclohydrolase I, which is the rate‐limiting enzyme for the biosynthesis of BH4, concomitantly with the loss of protective effect afforded by V‐1 overexpression. Furthermore, the addition of BH4or sepiapterin to DAHP‐pretreated V146 and V1‐69 cells restored cell viability. Taken together, these results indicate that V1 protein plays an important role in protection against cell death induced by NO at low levels by promoting the synthesis of BH4. Moreover, these findings suggest the up‐regulation of V1 expression as a possible therapeutic target for protection against the insult of NO‐induced oxidative stress. © 2003 Wiley‐Liss, Inc.
Expression of depolarization‐induced immediate early gene proteins in PC12 cells
Authors: Liu Wei , Feldman Jonathan D. , Machado Hidevaldo B. , Vician Linda J. , Herschman Harvey R.
Published: May 2003

Immediate early genes induced by depolarization are thought to be important in mediating neuronal functional plasticity. We previously identified a group of immediate early genes that are preferentially induced by depolarization and forskolin but not by nerve growth factor or epidermal growth factor in PC12 pheochromocytoma cells. These depolarization‐induced genes include synaptotagmin 4; the protein kinases KID‐1, PIM‐1, and SIK; an orphan transcription factor, Nurr‐1; and a transcription corepressor, rTLE‐3. All these genes are also induced in the hippocampus in response to kainic‐acid induced depolarization. To characterize further the unique functions of these genes in plasticity, we used recombinant proteins to generate and purify antibodies against KID‐1 and SIK proteins. Immunoblotting experiments were performed to examine the induced expression of the KID‐1 and SIK proteins in PC12 cells. PIM‐1 and Nurr‐1 protein expression was also examined following stimulation, using commercially available antibodies. There is an increase in synthesis, in PC12 cells, of these four IEG proteins after KCl plus forskolin treatment. Nurr‐1 protein peaks between 2 and 4 hr and decreases by 6 hr after the treatment. PIM‐1 and KID‐1 proteins rise by 1 hr, peak between 2 and 4 hr, and return to their basal levels at 6 hr. SIK protein increases significantly at 2 hr after treatment, peaks between 4 and 6 hr, and returns to the basal level at 8 hr. Immunofluorescence studies demonstrate distinct distribution patterns of each of these depolarization‐induced IEG proteins in PC12 cells. © 2003 Wiley‐Liss, Inc.
Oligodendrocyte progenitor migration in response to injury of glial monolayers requires the polysialic neural cell‐adhesion molecule
Authors: Barral‐Moran M.‐J. , Calaora V. , Vutskits L. , Wang C. , Zhang H. , Durbec P. , Rougon G. , Kiss J.Z.
Published: May 2003

Injury to the nervous system results in reactive astrogliosis that is a critical determinant of neuronal regeneration. To analyze glial responses to mechanical injury and the role of the polysialic neural cell adhesion molecule (PSA‐NCAM) in this process, we established primary glia cultures from newborn rat cerebral cortex. Scratching a confluent monolayer of primary glial cells resulted in two major events: rapid migration of oligodendrocyte progenitor‐like (O‐2A) cells into the wounded area and development of polarized morphology of type 1 astrocytes at the wound edge. Migrating O‐2A progenitors had a bipolar morphology and exhibited A2B5 and O4 immunolabeling. Once these cells were established inside the wounded area, they lost A2B5 immunoreactivity and differentiated into glial fibrillary acidic protein‐positive astrocytes. Migrating O‐2A cells expressed PSA‐NCAM, but type 1 astrocytes at the wound edge did not. Treatment of wounded cultures with Endo‐N, which specifically removes PSA from the surface of cells, resulted in a significant decrease in O‐2A cell migration into the wounded area and completely blocked the wound closure. Video time‐lapse analysis showed that, in the presence of Endo‐N, O‐2A cells remained motile and migrated short distances but did not move away from the monolayer. These results demonstrate that O‐2A progenitors contribute to reactive astrogliosis in culture and that PSA‐NCAM is involved in this process by regulating cell migration. © 2003 Wiley‐Liss, Inc.
Grafted swine neuroepithelial stem cells can form myelinated axons and both efferent and afferent synapses with xenogeneic rat neurons
Authors: Uchida Koichi , Okano Hideyuki , Hayashi Takuro , Mine Yutaka , Tanioka Yoshikuni , Nomura Tatsuji , Kawase Takeshi
Published: May 2003

Neuroepithelial stem cells derived from the swine mesencephalic neural tube were examined regarding their eligibility for neural xenografting as a donor material, with the aim of evaluating myelinated axon formation and both types of synaptic formation with xenogeneic host neurons as part of possible neural circuit reconstruction. The mesencephalic neural tube tissues were dissected out from swine embryos at embryonic days 17 and 18 and were implanted immediately into the striatum of the Parkinsonian model rat. The swine‐derived grafts had many nestin‐positive rosette‐forming, neurofilament‐positive, and tyrosine hydroxylase‐positive cells in the rat striatum. Electron microscopic study revealed both efferent and afferent synaptic formations in the donor‐derived immature neurons or tyrosine hydroxylase‐positive donor cells in the grafts. Myelinated axons, both positive and negative for swine‐specific neurofilament antibody, were mingled together in the graft. These results indicated that implanted neuroepithelial stem cells could survive well and divide asymmetrically into both nestin‐expressing precursors and differentiated neurochemical marker‐expressing neurons in the xenogeneic rat striatum, with the help of an immunosuppressant. Donor‐derived immature neurons formed both efferent and afferent synapses with xenogeneic host neurons, and donor‐derived axons were myelinated, which suggests that implanted swine neuroepithelial stem cells could possibly restore damaged neuronal circuitry in the diseased brain. © 2003 Wiley‐Liss, Inc.
Cyclic AMP responsive element binding protein phosphorylation and persistent expression of levodopa‐induced response alterations in unilateral nigrostriatal 6‐OHDA lesioned rats
Authors: Oh Justin D. , Chartisathian Karnon , Ahmed Syed M. , Chase Thomas N.
Published: May 2003

Activation of cAMP responsive element binding protein (CREB) has been increasingly implicated in the formation and maintenance of long‐term memory. To elucidate molecular mechanisms that underlie the persisting alterations in motor response occurring with levodopa (L‐dopa) treatment of parkinsonian patients, we evaluated the time course of these changes in relation to the activation of striatal CREB in 6‐hydroxydopamine (6‐OHDA) lesioned animals. Three weeks of twice‐daily L‐dopa treatment reduced the duration of the rotational response to acute L‐dopa challenge in hemiparkinsonian rats, which lasted about 5 weeks after withdrawal of chronic L‐dopa therapy. This shortened response duration, resembling human wearing‐off fluctuations, was associated with a marked increase in Ser‐133 phosphorylated CREB (pCREB) immunoreactivity in medium spiny neurons in dorsolateral striatum in response to acute dopaminomimetic challenge. Intermittent treatment with the D1 receptor‐preferring agonist SKF 38393, but not the D2 receptor‐preferring agonist quinpirole, produced a similar rise in CREB phosphorylation. The time course of changes in CREB phosphorylation correlated with the time course of changes in motor behavior after cessation of chronic L‐dopa therapy. Both the altered motor response duration and the degree of CREB phosphorylation were attenuated by the intrastriatal administration of CREB antisense or protein kinase A inhibitor Rp‐cAMPS. The results suggest that region‐specific Ser‐133 CREB phosphorylation in D1 receptor containing spiny neurons contributes to the persistence of the motor response alterations produced by intermittent stimulation of striatal dopaminergic receptors. © 2003 Wiley‐Liss, Inc.
Transcription profiling reveals mitochondrial, ubiquitin and signaling systems abnormalities in postmortem brains from subjects with a history of alcohol abuse or dependence
Authors: Sokolov Boris P. , Jiang Lixin , Trivedi Niraj S. , Aston Christopher
Published: May 2003

Alcohol abuse is a common human disorder with high rate of comorbidity with other psychiatric disorders. To identify candidate mechanisms for alcohol abuse, the expression of 12,626 genes was measured in postmortem temporal cortex from 11 subjects with a history of alcohol abuse or dependence, with or without other psychiatric diagnoses and compared pairwise with the expression in 11 nonalcoholic subjects matched for the other psychiatric diagnoses and demographics. Genes were defined to have altered expression in alcohol abuse if: 1) the gene showed decreased expression in at least 10 of 11 subjects with alcohol abuse, or showed increased expression in at least 10 of 11 subjects with this diagnosis compared to matched non‐abusers (P < 0.007, χ2test); or 2) the difference in the mean abuser/non‐abuser ratio for the gene from value of 1.0 was significant at P < 0.05 (one sample t‐test). In subjects with a history of alcohol abuse or dependence, 163 genes were changed significantly. The most abundant and consistent changes were in gene families encoding mitochondrial proteins, the ubiquitin system, and signal transduction. These alterations indicate disturbances in energy metabolism and multiple signaling mechanisms in the temporal cortex of subjects with a history of alcohol abuse or dependence. We hypothesize that these mechanisms may be related to alcohol abuse traits or long‐term effects of alcohol. © 2003 Wiley‐Liss, Inc.
Understanding strategies for the improvement of inter‐organizational performance: cases from the air transport industry
Authors: Saxton Peter J. , Korac‐Kakabadse Nada
Published: May 2003

In the increasingly globalized economy there can be few organizations that have no need to interact with other organizations. In modern business, interaction with other organizations is virtually unavoidable. The ability to manage inter‐organizational affairs effectively might be a capability critical to the success of the organization.

This paper presents an enquiry into inter‐organizational management. The aim of the enquiry was to identify and understand strategies that might improve inter‐organizational performance with monopoly suppliers, a context often seen as particularly difficult by practitioners and managers.

The central purpose was to discover whether there exist any principles that might be generally applied by managers to improve the performance of inter‐organizationally managed processes. The research is based on two case studies of the management of baggage systems, one at London Heathrow Airport and the second at London Gatwick Airport.

The Heathrow case was selected as an example of an operation where successful cooperation had been achieved. Gatwick was selected as a comparison because the cooperation within this operation was problematic. The paper concludes that there are principles that can be applied to different circumstances to improve inter‐organizational performance. Copyright © 2003 John Wiley &Sons, Ltd.
Grounding strategic change practice in theory: the case of Avaya Ireland, 1992–2000
Authors: Dwyer Graham , Heracleous Loizos , Doyle Ciaran
Published: May 2003

The Avaya Ireland story generates insights about how the European Foundation for Quality Management Model can be mobilized as a vehicle for driving organizational change. This paper describes the process of strategic change at Avaya Ireland and grounds the practical experience in recent strategic change management literature.

The process of linking strategic change management theory to practice adds richness to the analysis by illustrating how radical change can be brought about by a perceived crisis based on changing environmental conditions. It also illustrates the use of applied frameworks by the organization as a guide for structuring and motivating strategic change. Copyright © 2003 John Wiley & Sons, Ltd.
The origin of species ‘competitive advantage’
Authors: Franklin Peter , Fredericks John
Published: May 2003

This is the first of two papers relating to the idea and theory of competitive advantage. In this paper, the principal task is to return to basics and reveal some of the intellectual foundations to the concept of competitive advantage.

In particular it is shown that the theory of competition, which informs the development of industrial economics, and Porter's (1980, 1985) work on competitive advantage entails profound methodological problems that bring into doubt the validity and reliability of the theory itself.

It is therefore argued that any theory that relies on competition theory, including the theory of competitive advantage, will inherit the flaws of its origins. Copyright © 2003 John Wiley &Sons, Ltd.
Strategic change in the ambulance service: barriers and success strategies for the implementation of high‐performance management systems
Authors: Woollard Malcolm , Lewis Duncan , Brooks Simon
Published: May 2003

This paper examines how high‐performance management (HPM) strategies might increase operational and service efficiency in a large UK ambulance National Health Service (NHS) Trust.

Ambulance services are faced with a government imposition of response times and increasing numbers of emergency calls. This paper reports on the change barriers as perceived by staff and middle management.

Using a mixture of focus groups and semi‐structured interviews, the results point to barriers to change including, staff resistance to new working practices, a perceived lack of expertise among some middle managers and poor communication between staff and managers.

Proposed success strategies included communication of the benefits of HPM to staff, the provision of a 24‐hour management presence and greater staff involvement. Copyright © 2003 John Wiley & Sons, Ltd.
Capillary liquid chromatography as a tool for separation of hydrophobic basic drugs. Relation between tests for column characterization and real analysis
Authors: Kafková Bozena , Tesařová Eva , Suchánková Jana , Bosáková Zuzana , Coufal Pavel
Published: June 2003

Two capillary columns for reversed phase (RP) capillary liquid chromatography (CLC), viz. Nucleosil 100‐5 C18 and LiChrosorb RP‐select B, were characterized by the Walters test, i.e. the chromatographic test proposed for RP stationary phases. Hydrophobicity indices were determined not only in acetonitrile/water mobile phase, as proposed in the test, but they were also measured in buffered systems. This approach was used to quantify the influence of mobile phase composition on the modification of the surface of the stationary phases. In the next step, small basic compounds differing in their hydrophobicity and basicity were selected and their retention on the stationary phases in mobile phases of the same composition as used for column testing was examined. Furthermore, the retention of newly synthesized drugs, chemotherapeutics derived from thioacridine and pyridoquinoline, differing in their structures, basicity, and hydrophobicity, was also studied. The composition of the mobile phases had to be shifted to higher contents of organic modifiers – acetonitrile or methanol – in order to elute these hydrophobic compounds from the columns. The question we wanted to answer was: How is the method for testing of reversed phases related to retention, separation efficiency, and peak symmetry of various analytes?