bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diazoxide induces delayed pre‐conditioning in cultured rat cortical neurons
Authors: Kis Bela , Rajapakse Nishadi C. , Snipes James A. , Nagy Krisztina , Horiguchi Takashi , Busija David W. 
Published: November 2003

AbstractWe investigated the effect of diazoxide on neuronal survival in primary cultures of rat cortical neurons against oxygen–glucose deprivation (OGD). Diazoxide pre‐treatment induced delayed pre‐conditioning and almost entirely attenuated the OGD‐induced neuronal death. Diazoxide inhibited succinate dehydrogenase and induced mitochondrial depolarization, free radical production and protein kinase C activation. The putative mitochondrial ATP‐sensitive potassium channel blocker 5‐hydroxydecanoate abolished the protective effect of diazoxide while the non‐selective KATP channel blocker glibenclamide did not. The non‐selective KATP channel openers nicorandil and cromakalim did not improve viability. Superoxide dismutase mimetic, M40401, or protein kinase C inhibitor, chelerythrine, prevented the neuroprotective effect of diazoxide. Diazoxide did not increase reduced glutathione and manganese‐superoxide dismutase levels but we found significantly higher reduced glutathione levels in diazoxide‐pre‐conditioned neurons after OGD. In pre‐conditioned neurons free radical production was reduced upon glutamate stimulation. The succinate dehydrogenase inhibitor 3‐nitropropionic acid also induced pre‐conditioning and free radical production in neurons. Here, we provide the first evidence that diazoxide induces delayed pre‐conditioning in neurons via acute generation of superoxide anion and activation of protein kinases and subsequent attenuation of oxidant stress following OGD. The succinate dehydrogenase‐inhibiting effect of diazoxide is more likely to be involved in this neuroprotection than the opening of mitochondrial ATP‐sensitive potassium channels.
The myelin–axolemmal complex: biochemical dissection and the role of galactosphingolipids
Authors: Menon Krishna , Rasband Matthew N. , Taylor Christopher M. , Brophy Peter , Bansal Rashmi , Pfeiffer Steven E. 
Published: November 2003

AbstractMyelin–axolemmal interactions regulate many cellular and molecular events, including gene expression, oligodendrocyte survival and ion channel clustering. Here we report the biochemical fractionation and enrichment of distinct subcellular domains from myelinated nerve fibers. Using antibodies against proteins found in compact myelin, non‐compact myelin and axolemma, we show that a rigorous procedure designed to purify myelin also results in the isolation of the myelin–axolemmal complex, a high‐affinity protein complex consisting of axonal and oligodendroglial components. Further, the isolation of distinct subcellular domains from galactolipid‐deficient mice with disrupted axoglial junctions is altered in a manner consistent with the delocalization of axolemmal proteins observed in these animals. These results suggest a paradigm for identification of proteins involved in neuroglial signaling.
Caspase activation contributes to delayed death of heat‐stressed striatal neurons
Authors: White Michael G. , Emery Michael , Nonner Doris , Barrett John N. 
Published: November 2003

AbstractHyperthermia can contribute to brain damage both during development and post‐natally. We used rat embryonic striatal neurons in culture to study mechanisms underlying hyperthermia‐induced neuronal death. Heat stress at 43°C for 2 h produced no obvious signs of damage during the first 12 h after the stress, but more than 50% of the neurons died during the next 3 days. More than 40% of the neurons had activated caspases 24 h following the heat stress. Caspase‐3 activity increased with a delay of more than 10 h following cessation of the heat stress, reaching a peak at ∼18 h. Neuronal death measured 1–3 days after the stress was reduced by the general caspase inhibitors qVD‐OPH (10–20 µm) and zVAD‐fmk (50–100 µm). These inhibitors were protective even when added 9 h after cessation of the heat stress, consistent with the delayed activation of caspases. In contrast, blockers of Na+ channels and ionotropic glutamate receptors did not reduce the heat‐induced death, indicating that glutamate excitotoxicity was not required for this neuronal death. These results show that the neuronal death produced by heat stress has characteristics of apoptosis, and that caspase inhibitors can delay this death.
Free radical‐dependent nuclear localization of Bcl‐2 in the central nervous system of aged rats is not associated with Bcl‐2‐mediated protection from apoptosis
Authors: Kaufmann Joel A. , Perez Mike , Zhang WenRu , Bickford Paula C. , Holmes Douglas B. , Taglialatela Giulio 
Published: November 2003

AbstractWe have previously reported that Bcl‐2 is up‐regulated in the CNS of aged F344 rats as a consequence of oxidative stress. In addition to increased levels of expression, we now report that there is a subcellular redistribution of Bcl‐2 in the CNS of aged F344 rats. Using western blotting, we found Bcl‐2 predominantly located in the cytosol of young rats. However, in aged rats Bcl‐2 was found primarily in the nucleus. This distribution, in the hippocampus and cerebellum, was reversed by treatment with the nitrone spin trap N‐tert‐butyl‐α‐phenylnitrone (PBN). Paradoxically, PBN treatment in young rats had the opposite effect, changing Bcl‐2 from predominantly cytosolic to nuclear. We also detected an increase in Bax in aged hippocampal samples (both nuclear and cytosolic), which was reversed by treatment with PBN. The distribution of Bcl‐2 and Bax in the cytosol of aged rats dramatically decreased the Bcl‐2/Bax ratio, a probable indicator of neuronal vulnerability, which was restored upon treatment with PBN. In order to assess the effect of nuclear association of Bcl‐2 we used PC12 cells stably transfected with a Bcl‐2 construct to which we added the nuclear localization sequence of the SV40 large T antigen to the N‐terminus which resulted in nuclear targeting of Bcl‐2. Measurement of cell death using lactate dehydrogenase assays showed that, contrary to wild‐type Bcl‐2, Bcl‐2 localized to the nucleus was not effective in protecting cells from treatment with 250 µm H2O2. These results suggest that nuclear localization of Bcl‐2 observed in the aged CNS may not reflect a protective mechanism against oxidative stress, a major component of age‐associated CNS impairments.
Androgens modulate β‐amyloid levels in male rat brain
Authors: Ramsden M. , Nyborg A. C. , Murphy M. P. , Chang L. , Stanczyk F. Z. , Golde T. E. , Pike C. J. 
Published: November 2003

AbstractAs a normal consequence of aging, men experience a significant decline in androgen levels. Although the neural consequences of age‐related androgen depletion remain unclear, recent evidence suggests a link between low androgen levels and the development of Alzheimer's disease (AD). Here, we test the hypothesis that androgens act as endogenous modulators of β‐amyloid protein (Aβ) levels. To investigate this possibility, brain and plasma levels of Aβ were measured in male rats with varying hormonal conditions. Depletion of endogenous sex steroid hormones via gonadectomy (GDX) resulted in increased brain levels of Aβ in comparison to gonadally intact male rats. This GDX‐induced increase in Aβ levels was reversed by DHT supplementation, demonstrating a functional role for androgens in modulating brain levels of Aβ. These findings suggest that age‐related androgen depletion may result in accumulation of Aβ in the male brain and thereby act as a risk factor for the development of AD.
Short Course of Prednisolone in Indian Patients with Solitary Cysticercus Granuloma and New‐onset Seizures
Authors: Mall Ravi Kant , Agarwal Atul , Garg Ravindra Kumar , Kar Alok Mohan , Shukla Rakesh 
Published: November 2003

Summary:  Purpose: To evaluate the role of a short course of oral corticosteroids in Indian patients with solitary cysticercus granuloma with seizures. Methods: In this open‐label, randomized, prospective follow‐up study, 97 patients with new‐onset seizures and a single enhancing computed tomography (CT)‐detected lesion of cysticercosis were randomly divided in two groups to receive either antiepileptic monotherapy alone (n = 48) or antiepileptic monotherapy with prednisolone (n = 49). The patients in the latter group received prednisolone, 1 mg/kg/day for 10 days, followed by tapering over next 4 days. The patients were followed up for 6 months. Repeated CT scans were performed after 1 and 6 months. Results: The majority of patients were young. Simple partial seizure, with or without secondary generalization, was the commonest seizure type encountered. Follow‐up CT scans at 1 and 6 months demonstrated a significantly better response for prednisolone as far as complete resolution of CT lesion was concerned. Kaplan–Meier analysis suggested significantly less probability of seizure recurrence for prednisolone‐treated patients. At 6 months, Kaplan–Meier estimated risk of seizure after first seizure was 2% in prednisolone‐treated patients in comparison to 13% for those who were not given prednisolone. Conclusions: Short‐term prednisolone therapy helps in rapid resolution of solitary cysticercus granuloma in Indian patients with new‐onset seizures. Resolution of lesions is associated with improved seizure‐related prognosis.
The Multicenter Study of Epilepsy Surgery: Recruitment and Selection for Surgery
Authors: Berg Anne T. , Vickrey Barbara G. , Langfitt John T. , Sperling Michael R. , Walczak Thaddeus S. , Shinnar Shlomo , Bazil Carl W. , Pacia Steven V. , Spencer Susan S. ,   Multicenter Study of Epilepsy Surgery
Published: November 2003

Summary:  Purpose: Multiple studies have examined predictors of seizure outcomes after epilepsy surgery. Most are single‐center series with limited sample size. Little information is available about the selection process for surgery and, in particular, the proportion of patients who ultimately have surgery and the characteristics that identify those who do versus those who do not. Such information is necessary for providing the epidemiologic and clinical context in which epilepsy surgery is currently performed in the United States and in other developed countries. Methods: An observational cohort of 565 surgical candidates was prospectively recruited from June 1996 through January 2001 at six Northeastern and one Midwestern surgical centers. Standardized eligibility criteria and protocol for presurgical evaluations were used at all seven sites. Results: Three hundred ninety‐six (70%) study subjects had resective surgery. Clinical factors such as a well‐localized magnetic resonance imaging (MRI) abnormality and consistently localized EEG findings were most strongly associated with having surgery. Of those who underwent intracranial monitoring (189, 34%), 85% went on to have surgery. Race/ethnicity and marital status were marginally associated with having surgery. Age, education, and employment status were not. Demographic factors had little influence over the surgical decision. More than half of the patients had intractable epilepsy for ≥10 years and five or more drugs had failed by the time they initiated their surgical evaluation. During the recruitment period, eight new antiepileptic drugs were approved by the Food and Drug Administration for use in the United States and came into increasing use in this study's surgical candidates. Despite the increased availability of new therapeutic options, the proportion that had surgery each year did not fluctuate significantly from year to year. This suggests that, in this group of patients, the new drugs did not provide a substantial therapeutic benefit. Conclusions: Up to 30% of patients who undergo presurgical evaluations for resective epilepsy surgery ultimately do not have this form of surgery. This is a group whose needs are not currently met by available therapies and procedures. Lack of clear localizing evidence appears to be the main reason for not having surgery. To the extent that these data can address the question, they suggest that repeated attempts to control intractable epilepsy with new drugs will not result in sustained seizure control, and eligible patients will proceed to surgery eventually. This is consistent with recent arguments to consider surgery earlier rather than later in the course of epilepsy. Postsurgical follow‐up of this group will permit a detailed analysis of presurgical factors that predict the best and worst seizure outcomes.
Antiproliferative Coatings for the Treatment of Coronary Heart Disease:
Authors: SMITH ELLIOT J. , ROTHMAN MARTIN T. 
Published: November 2003

Since the advent of percutaneous coronary intervention (PCI) for stenosing coronary disease, restenosis has remained a clinical problem. Despite the emergence and evolution of coronary stents, the rate of restenosis following PCI is still 10–20%, and above 50% in high risk subgroups. With increased understanding of the pathophysiology of this process, a number of potential therapeutic targets have been identified, allowing the development of novel therapies against restenosis, which can now be delivered locally using stent platforms. Some of the reported clinical trial data utilizing drug‐eluting stents (DES) have produced such profound reductions in clinical and angiographic restenosis that we have been tempted to believe we are on the brink of eradicating this process completely. As the initial excitement subsides, however, there is a need to decide whether these tools will remain effective in real‐world interventional practice. In this article we review the pathophysiology of the restenotic process, and the biological targets of the DES therapies currently available in clinical practice. We attempt to define clinical target populations for DES therapy, and assess the impact on outcomes thus far. We consider the advantages that newly emergent stent coatings might offer, and whether targeting specific patient subgroups with unique antiproliferative agents may provide the best chance of limiting restenosis in high risk subgroups. Finally, we consider future strategies to prevent restenosis, with a movement away from the antiproliferative approach, and toward accelerating endothelialization. (J Interven Cardiol 2003;16:475–483)
Children's counterfactual inferences about long and short causal chains
Authors: German Tim P. , Nichols Shaun 
Published: November 2003

Abstract Recent findings on counterfactual reasoning in children have led to the claim that children's developing capacities in the domain of ‘theory of mind’ might reflect the emergence of the ability to engage in counterfactual thinking over the preschool period (e.g. Riggs, Peterson, Robinson & Mitchell, 1998). In the study reported here, groups of 3‐ and 4‐year old children were presented with stories describing causal chains of several events, and asked counterfactual thinking tasks involving changes to different points in the chain. The ability to draw successful counterfactual inferences depended strongly on the inferential length of the problem, and the age of the children; while 3‐year‐olds performed above chance on short inference counterfactuals, they performed below chance on problems involving longer inference chains. Four‐year‐old children were above chance on all problems. Moreover, it was found that while success on longer chain inference problems was significantly correlated with the ability to pass tests of standard false belief, there was no such relationship for short inference problems, which were significantly easier than false belief problems. These results are discussed in terms of the developmental relationships between causal knowledge, counterfactual thinking and calculating the contents of mental states.
Recognition, discrimination and categorization of smiling by 5‐month‐old infants
Authors: Bornstein Marc H. , Arterberry Martha E. 
Published: November 2003

AbstractPerceiving emotions correctly is foundational to the development of interpersonal skills. Five‐month‐old infants’ abilities to recognize, discriminate and categorize facial expressions of smiling were tested in three coordinated experiments. Infants were habituated to four degrees of smiling modeled by the same or different people; following habituation, infants were presented with a new degree of smile worn by the same and by a new person (Experiment 1), a new degree of smile and a fearful expression worn by the same person (Experiment 2) or a new degree of smile and a fearful expression worn by new people (Experiment 3). Infants showed significant novelty preferences for the new person smiling and for the fearful expressions over the new degree of smiling. These findings indicate that infants at 5 months can categorize the facial expression of smiling in static faces, and yet recognize the same person despite changes in facial expression; this is the youngest age at which these abilities have been demonstrated. The findings are discussed in light of the significance of emotion expression face processing in social interaction and infants’ categorization of faces.
Marketisation in Higher Education, Clark's Triangle and the Essential Ingredients of Markets
Authors: Jongbloed Ben 
Published: November 2003

AbstractWhile government intervention in the higher education market may be justified, it may come at the cost of lower consumer sovereignty and restricted producer autonomy. Through marketisation policy, students and higher education providers have more room to make their own trade‐offs and interact more closely on the basis of reliable information. This article discusses eight conditions for a market and the extent to which these are met in Dutch higher education. It is argued that there is still a key role for the government to co‐design framework conditions and facilitate interaction in a more demand‐driven and liberalised higher education sector.
Allowing the Market to Rule: The Case of the United States
Authors: Dill David D. 
Published: November 2003

AbstractThere are increasing calls in the UK and other countries for deregulating universities so that they can better compete in the global market for higher education. Frequent allusions are made to the superiority of the US market‐oriented system. But is market competition for first degrees in the US efficient for the larger society? Do the constantly increasing social expenditures for higher education in the US benefit the public interest or do they advantage certain students and faculty members? Two recent economic studies provide greater insight into the impacts of market competition on US higher education. The results of these studies are discussed and their possible implications for higher education policy making in other countries are explored.
Use of Bacterial γ-Glutamyltranspeptidase for Enzymatic Synthesis of γ-d-Glutamyl Compounds
Authors: Suzuki Hideyuki , Izuka Shunsuke , Minami Hiromichi , Miyakawa Nobukazu , Ishihara Sayaka , Kumagai Hidehiko 
Published: November 2003

ABSTRACTAn enzymatic method for synthesizing various γ-d-glutamyl compounds efficiently and stereospecifically involving bacterial γ-glutamyltranspeptidase (EC 2.3.2.2) withd-glutamine as a γ-glutamyl donor was developed. Withd-glutamine as a γ-glutamyl donor instead ofl-glutamine in γ-glutamyltaurine synthesis, by-products such as γ-glutamylglutamine and γ-glutamyl-γ-glutamyltaurine were not synthesized and the yield of γ-glutamyltaurine dramatically increased from 25 to 71%. It was also shown that the purification could be simplified without these γ-glutamyl by-products. The possibility of synthesizing various γ-d-glutamyl compounds was also shown.
Anaerobic Ammonium Oxidation Measured in Sediments along the Thames Estuary, United Kingdom
Authors: Trimmer Mark , Nicholls Joanna C. , Deflandre Bruno 
Published: November 2003

ABSTRACT

Until recently, denitrification was thought to be the only significant pathway for N
2
formation and, in turn, the removal of nitrogen in aquatic sediments. The discovery of anaerobic ammonium oxidation in the laboratory suggested that alternative metabolisms might be present in the environment. By using a combination of
15
N-labeled NH
4
+
, NO
3
−
, and NO
2
−
(and
14
N analogues), production of
29
N
2
and
30
N
2
was measured in anaerobic sediment slurries from six sites along the Thames estuary. The production of
29
N
2
in the presence of
15
NH
4
+
and either
14
NO
3
−
or
14
NO
2
−
confirmed the presence of anaerobic ammonium oxidation, with the stoichiometry of the reaction indicating that the oxidation was coupled to the reduction of NO
2
−
. Anaerobic ammonium oxidation proceeded at equal rates via either the direct reduction of NO
2
−
or indirect reduction, following the initial reduction of NO
3
−
. Whether NO
2
−
was directly present at 800 μM or it accumulated at 3 to 20 μM (from the reduction of NO
3
−
), the rate of
29
N
2
formation was not affected, which suggested that anaerobic ammonium oxidation was saturated at low concentrations of NO
2
−
. We observed a shift in the significance of anaerobic ammonium oxidation to N
2
formation relative to denitrification, from 8% near the head of the estuary to less than 1% at the coast. The relative importance of anaerobic ammonium oxidation was positively correlated (
P
< 0.05) with sediment organic content. This report of anaerobic ammonium oxidation in organically enriched estuarine sediments, though in contrast to a recent report on continental shelf sediments, confirms the presence of this novel metabolism in another aquatic sediment system.
Reactive Oxygen Species and Induction of Lignin Peroxidase in
Phanerochaete chrysosporium
Authors: Belinky Paula A. , Flikshtein Nufar , Lechenko Sergey , Gepstein Shimon , Dosoretz Carlos G. 
Published: November 2003

ABSTRACT

We studied oxidative stress in lignin peroxidase (LIP)-producing cultures (cultures flushed with pure O
2
) of
Phanerochaete chrysosporium
by comparing levels of reactive oxygen species (ROS), cumulative oxidative damage, and antioxidant enzymes with those found in non-LIP-producing cultures (cultures grown with free exchange of atmospheric air [control cultures]). A significant increase in the intracellular peroxide concentration and the degree of oxidative damage to macromolecules, e.g., DNA, lipids, and proteins, was observed when the fungus was exposed to pure O
2
gas. The specific activities of manganese superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase and the consumption of glutathione were all higher in cultures exposed to pure O
2
(oxygenated cultures) than in cultures grown with atmospheric air. Significantly higher gene expression of the LIP-H2 isozyme occurred in the oxygenated cultures. A hydroxyl radical scavenger, dimethyl sulfoxide (50 mM), added to the culture every 12 h, completely abolished LIP expression at the mRNA and protein levels. This effect was confirmed by in situ generation of hydroxyl radicals via the Fenton reaction, which significantly enhanced LIP expression. The level of intracellular cyclic AMP (cAMP) was correlated with the starvation conditions regardless of the oxygenation regimen applied, and similar cAMP levels were obtained at high O
2
concentrations and in cultures grown with atmospheric air. These results suggest that even though cAMP is a prerequisite for LIP expression, high levels of ROS, preferentially hydroxyl radicals, are required to trigger LIP synthesis. Thus, the induction of LIP expression by O
2
is at least partially mediated by the intracellular ROS.