bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of secretory phospholipase A2 in reactive astrocytes in response to transient focal cerebral ischemia in the rat brain
Authors: Lin Teng‐Nan , Wang Qun , Simonyi Agnes , Chen Jean‐Ju , Cheung Wai‐Mui , Y. He Yong , Xu Jan , Sun Albert Y. , Hsu Chung Y. , Sun Grace Y. 
Published: July 2004

AbstractAlthough mRNA expression of group IIA secretory phospholipase A2 (sPLA2‐IIA) has been implicated in responses to injury in the CNS, information on protein expression remains unclear. In this study, we investigated temporal and spatial expression of sPLA2‐IIA mRNA and immunoreactivity in transient focal cerebral ischemia induced in rats by occlusion of the middle cerebral artery. Northern blot analysis showed a biphasic increase in sPLA2‐IIA mRNA expression following 60‐min of ischemia–reperfusion: an early phase at 30 min and a second increase at a late phase ranging from 12 h to 14 days. In situ hybridization localized the early‐phase increase in sPLA2‐IIA mRNA to the affected ischemic cortex and the late‐phase increase to the penumbral area. Besides sPLA2‐IIA mRNA, glial fibrillary acidic protein (GFAP) and cyclo‐oxygenase‐2 mRNAs, but not cytosolic PLA2, also showed an increase in the penumbral area at 3 days after ischemia–reperfusion. Immunohistochemistry of sPLA2‐IIA indicated positive cells in the penumbral area similar to the GFAP‐positive astrocytes but different from the isolectin B4‐positive microglial cells. Confocal microscopy further confirmed immunoreactivity of sPLA2‐IIA in reactive astrocytes but not in microglial cells. Taken together, these results demonstrate for the first time an up‐regulation of the inflammatory sPLA2‐IIA in reactive astrocytes in response to cerebral ischemia–reperfusion.
Role of phospholipase D signaling in ethanol‐induced inhibition of carbachol‐stimulated DNA synthesis of 1321N1 astrocytoma cells
Authors: Guizzetti Marina , Thompson Brian D. , Kim Yunie , VanDeMark Kathryn , Costa Lucio G. 
Published: July 2004

AbstractInhibition of astrocyte proliferation has been suggested to be an important event in the developmental neurotoxicity associated with ethanol. We have previously shown that the acetylcholine analog carbachol induces astroglial cell proliferation through activation of muscarinic M3 receptors, and that ethanol strongly inhibits this effect by inhibiting activation of protein kinase C (PKC) ζ and its down‐stream effector 70‐kDa ribosomal S6 kinase (p70S6K). In this study, we investigated whether inhibition by ethanol of this signal transduction pathway in 1321N1 human astrocytoma cells may be due, at least in part, to inhibition of the formation of the PKC ζ activator phosphatidic acid (PA), which is formed by hydrolysis of phosphatidylcholine by phospholipase D (PLD). 1‐Butanol, which is a substrate for PLD and inhibits PA formation, inhibited carbachol‐induced cell proliferation and the underlying intracellular signaling, whereas its analog tert‐butanol, which is a poor substrate for PLD, was much less effective. In addition, exogenous PAs were able to increase DNA synthesis and to activate PKC ζ and p70S6K. Furthermore, in carbachol‐stimulated cells, ethanol increased the formation of phosphatidylethanol and inhibited the formation of PA. Taken together, these results indicate that PLD activation plays an important role in carbachol‐induced astroglial cell proliferation by generating the second messenger PA, which activates PKC ζ. Moreover, the effect of ethanol on carbachol‐induced proliferation appears to be mediated, at least in part, by its ability to interact with PLD leading to a decreased synthesis of PA.
Increased cerebral uptake and oxidation of exogenous βHB improves ATP following traumatic brain injury in adult rats
Authors: Prins M. L. , Lee S. M. , Fujima L. S. , Hovda D. A. 
Published: July 2004

AbstractThere is growing evidence of the brain's ability to increase its reliance on alternative metabolic substrates under conditions of energy stress such as starvation, hypoxia and ischemia. We hypothesized that following traumatic brain injury (TBI), which results in immediate changes in energy metabolism, the adult brain increases uptake and oxidation of the alternative substrate β‐hydroxybutyrate (βHB). Arterio‐venous differences were used to determine global cerebral uptake of βHB and production of 14CO2 from [14C]3‐βHB 3 h after controlled cortical impact (CCI) injury. Quantitative bioluminescence was used to assess regional changes in ATP concentration. As expected, adult sham and CCI animals with only endogenously available βHB showed no significant increase in cerebral uptake of βHB or 14CO2 production. Increasing arterial βHB concentrations 2.9‐fold with 3 h of βHB infusion failed to increase cerebral uptake of βHB or 14CO2 production in adult sham animals. Only CCI animals that received a 3‐h βHB infusion showed an 8.5‐fold increase in cerebral uptake of βHB and greater than 10.7‐fold increase in 14CO2 production relative to sham βHB‐infused animals. The TBI‐induced 20% decrease in ipsilateral cortical ATP concentration was alleviated by 3 h of βHB infusion beginning immediately after CCI injury.
GADD34 protein levels increase after transient ischemia in the cortex but not in the CA1 subfield: implications for post‐ischemic recovery of protein synthesis in ischemia‐resistant cells
Authors: Paschen Wulf , Hayashi Takeshi , Saito Atsushi , Chan Pak H. 
Published: July 2004

AbstractTransient cerebral ischemia is a pathological process whereby an irreversible suppression of protein synthesis is believed to contribute to the extent of cell death in vulnerable neurons. Endoplasmic reticulum (ER) dysfunction has been identified as being responsible for ischemia‐induced shut‐down of translation. Recovery from ER dysfunction is facilitated by GADD34, a protein that dephosphorylates eukaryotic initiation factor (eIF)2α‐P and thus reactivates protein synthesis. We investigated ischemia‐induced changes in GADD34 levels in wild‐type and Cu2+/Zn2+SOD (SOD1) over‐expressing rats. Transient global cerebral ischemia was induced by common carotid artery occlusion. Tissue samples were taken from the vulnerable hippocampal CA1 subfield and the resistant cerebral cortex of the right and left hemispheres for evaluation of changes ingadd34mRNA and GADD34 protein levels. In wild‐type animals, we found significantly lower GADD34 levels than in SOD1 transgenes but no differences ingadd34mRNA levels, implying that superoxides regulategadd34translation. After ischemia, GADD34 protein levels were significantly increased in the cortex but not in the CA1 subfield, and these changes occurred earlier in SOD1 transgenic than in wild‐type animals. The rise ingadd34mRNA levels did not differ in the cortex and CA1 subfield, implying thatgadd34expression is regulated at the translational level.
Vitamin E reduces amyloidosis and improves cognitive function in Tg2576 mice following repetitive concussive brain injury
Authors: Conte Valeria , Uryu Kunihiro , Fujimoto Scott , Yao Yuemang , Rokach Joshua , Longhi Luca , Trojanowski John Q. , Lee Virginia M‐Y. , McIntosh Tracy K. , Praticò Domenico 
Published: July 2004

AbstractTraumatic brain injury is a well‐recognized environmental risk factor for developing Alzheimer's disease. Repetitive concussive brain injury (RCBI) exacerbates brain lipid peroxidation, accelerates amyloid (Aβ) formation and deposition, as well as cognitive impairments in Tg2576 mice. This study evaluated the effects of vitamin E on these four parameters in Tg2576 mice following RCBI. Eleven‐month‐old mice were randomized to receive either regular chow or chow‐supplemented with vitamin E for 4 weeks, and subjected to RCBI (two injuries, 24 h apart) using a modified controlled cortical impact model of closed head injury. The same dietary regimens were maintained up to 8 weeks post‐injury, when the animals were killed for biochemical and immunohistochemical analyses after behavioral evaluation. Vitamin E‐treated animals showed a significant increase in brain vitamin E levels and a significant decrease in brain lipid peroxidation levels. After RBCI, compared with the group on regular chow, animals receiving vitamin E did not show the increase in Aβ peptides, and had a significant attenuation of learning deficits. This study suggests that the exacerbation of brain oxidative stress following RCBI plays a mechanistic role in accelerating Αβ accumulation and behavioral impairments in the Tg2576 mice.
The novel neuromodulator hydrogen sulfide: an endogenous peroxynitrite ‘scavenger’?
Authors: Whiteman Matthew , Armstrong Jeffrey S. , Chu Siew Hwa , Jia‐Ling Siau , Wong Boon‐Seng , Cheung Nam Sang , Halliwell Barry , Moore Philip K. 
Published: July 2004

AbstractHydrogen sulfide (H2S) is a well‐known cytotoxic gas. Recently it has been shown to stimulate N‐methyl‐d‐aspartate (NMDA) receptors to enhance long‐term potentiation suggesting a novel neuromodulatory role in vivo. Endogenous levels of H2S in the brain are reported to range between 10 and 160 µm. Considerably lower H2S levels are reported in the brains of Alzheimer's disease (AD) patients, where levels of brain protein nitration (probably mediated by peroxynitrite) are markedly increased. Activation of NMDA receptors leads to intracellular tyrosine nitration by peroxynitrite. Because H2S and peroxynitrite are important mediators in brain function and disease, we investigated the effects of the H2S ‘donor’, sodium hydrogen sulfide (NaSH) on peroxynitrite‐mediated damage to biomolecules and to cultured human SH‐SY5Y cells. H2S significantly inhibited peroxynitrite‐mediated tyrosine nitration and inactivation of α1‐antiproteinase to a similar extent to reduced glutathione at each concentration tested (30–250 µm). H2S also inhibited peroxynitrite‐induced cytotoxicity, intracellular protein nitration and protein oxidation in human neuroblastoma SH‐SY5Y cells. These data suggest that H2S has the potential to act as an inhibitor of peroxynitrite‐mediated processes in vivo and that the potential antioxidant action of H2S deserves further study, given that extracellular GSH levels in the brain are very low.
Semicarbazide‐sensitive amine oxidase: role in the vasculature and vasodilation afterin situinhibition
Authors: Vidrio H. 
Published: July 2004

Summary1 The characteristics of semicarbazide‐sensitive amine oxidase (SSAO) are reviewed and the unknown physiological or pathological role of this enzyme emphasized.2 The various mechanisms of action proposed for the vasodilator drug hydralazine are considered. In particular, the inhibitory action on various enzymes, related or not to cardiovascular function, are discussed.3 Studies linking inhibition of SSAO to hydralazine hypotension are reviewed and a general hypothesis relating both actions is presented. The hypothesis postulates that (a) vascular SSAO is involved in the regulation of vascular tone, and (b) hydralazine vasodilation is the consequence of vascular SSAO inhibition.4 Evidence supporting these postulates is presented and vascular SSAO inhibition is proposed as a novel mechanism of vasodilation.
AT1‐receptor blockade and sympathetic neurotransmission in cardiovascular disease
Authors: Nap A. , Balt J. C. , Mathy M. J. , Van Zwieten P. A. 
Published: July 2004

Summary 1 The present survey is dealing with the interactions between the renin–angiotensin–aldosterone system (RAAS) and the sympathetic nervous system (SNS) in various organs and tissues, with an emphasis on the angiotensin AT‐receptors located at the sympathetic nerve endings. 2 Angiotensin II, the main effector of the RAAS is known to stimulate sympathetic nerve traffic and its sequelae in numerous organs and tissues, such as the central nervous system, the adrenal medulla, the sympathetic ganglia and the sympathetic nerve endings. These stimulatory effects are mediated by AT1‐receptors and counteracted by AT1‐receptor antagonists. 3 Sympatho‐inhibition at the level of the sympathetic nerve ending appears to be a class effect of the AT1‐receptor blockers, mediated by presynaptic AT1‐receptors. With respect to the ratio pre‐/postsynaptic AT1‐receptor antagonism important quantitative differences between the various compounds were found. 4 Both the pre‐ and postjunctional receptors at the sympathetic nerve endings belong to the AT1‐receptor population. However, the presynaptic receptors belong to the AT1B‐subtype, whereas the postjunctional receptors probably belong to a different AT1‐receptor subpopulation. 5 Sympatho‐inhibition is a class effect of the AT1‐receptor antagonists. In conditions in which the SNS plays a pathophysiological role, such as hypertension and congestive heart failure, this property may well be of therapeutic relevance.
Differential regulation by Ca2+ of calmodulin‐ and PKC‐dependent contractile pathways in cat lower oesophageal sphincter
Authors: Sohn U. D. , Park J. H. , Lee T. S. , Shin C. Y. , Jeong J. H. , Kim J. H. , Je H. D. , Dartt D. A. , Zoukhri D. , Choi H. C. , Lee K. Y. 
Published: July 2004

Summary 1 In the present investigation we examined the regulation of calmodulin (CaM)‐ and protein kinase C (PKC)‐dependent pathways by cytosolic Ca2+ in the contraction of cat lower oesophageal sphincter (LES). 2 Force developed in response to increasing doses of acetylcholine (ACh) was directly related to the increase of the [Ca2+]i measured by fura‐2. Thapsigargin, which depletes Ca2+ stores, reduced the contraction and the [Ca2+]i. In addition, contraction in response to maximal ACh was reduced by the CaM inhibitor CGS9343B but not by the PKC inhibitor chelerythrine. The contraction in response to submaximal ACh was reduced by chelerythrine but not by CGS9343B. 3 In permeabilized cells, the contraction in response to low Ca2+ (0.54 μm) was also reduced by CGS9343B. 4 The response to high Ca2+ (1.0 μm) was reduced by CGS9343B. ACh also inhibited PKC activation induced by diacylglycerol, which activation is inhibited by the N‐myristoylated peptide inhibitor derived from pseudosubstrate sequences of PKCαβγ (myr‐PKC‐αβγ), but not of myr‐PKC‐α. 5 These data are consistent with the view that activated CaM‐dependent pathways inhibit PKC‐dependent pathways, this switch mechanism might be regulated by Ca2+ in the LES.
Co‐localization of histamine and dopamine‐β‐hydroxylase in sympathetic ganglion and release of histamine from cardiac sympathetic terminals of guinea‐pig
Authors: Li M. , Luo X. , Chen L. , Zhang J. , Hu J. , Lu B. 
Published: July 2004

Summary 1 The aim of this study was to investigate the co‐localization of histamine and dopamine‐β‐hydroxylase in the superior cervical ganglion of guinea‐pig and release of histamine from cardiac sympathetic terminals in guinea‐pig isolated atrium. 2 Histidine decarboxylase (a histamine‐synthesizing enzyme) mRNA signals were detected in the neurones of superior cervical ganglion of guinea‐pig by in situ hybridization. The results of double‐labelled immunofluorescence further confirmed the co‐localization of histamine and dopamine‐β‐hydroxylase in the large principle neurons and small intensely fluorescent cells in the superior cervical ganglion. The immunoreactivities of both histamine and dopamine‐β‐hydroxylase were significantly attenuated after 6‐hydroxydopamine‐induced lesion of sympathetic nerves. 3 The refractory electrical field stimulation caused the release of histamine from cardiac sympathetic terminals of guinea‐pig isolated atria (112.14 ± 40.34 ng ml−1), which was significantly attenuated to 35 ± 15.57 ng ml−1 by reserpine pretreatment. Following administering compound 48/80, a mast cell degranulator, electrical field stimulation induced a dramatic increase of endogenous histamine release from isolated atria (303.57 ±72.93 ng ml−1). When compound 48/80 was added to the reserpine‐treated atria, the release of histamine induced by field stimulation was decreased to 207.14 ± 76.39 ng ml−1. 4 These results provide novel evidence that histamine co‐exists with noradrenaline in sympathetic nerves and might act as a neurotransmitter to modulate sympathetic neurotransmission.
Solitude and the Restlessness of the Immemorial: Levinasian Traces in the Discourse of Patrick Modiano
Authors: Levy Karen D. 
Published: July 2004

Emmanuel Levinas contested Western ontology's insistence on the importance of individual autonomy and systematized knowledge, developing a new description of how identity and intersubjectivity are constructed. In the early De l'existence à l'existant and Le Temps et l'autre, he explains how the effort of existing is assumed, creating a sense of mastery but also of solitude, for the ego and the self are tied to one another, but it is not until Totalité et Infini that he elaborates on the ethical encounter with the face as discourse. In his last major work Autrement qu’être ou au‐delà de l'essence, he focuses on the consequences of this epiphany for the subject, and relates this to the trace, a special kind of sign that focuses not so much on the relationship between sign and referent as on the irreversible passing of those who left them.The paired texts of Patrick Modiano's Voyage de noces and Dora Bruder most strikingly inscribe the simultaneous self‐absorption and tedium of existing, but also depict how traces from the immemorial shatter the subject's autonomy. Modiano is haunted by the missing person ad's description of a runaway girl who disappeared in December 1941, was interned in Drancy the following summer and then deported to Auschwitz. He first wrote Voyage de noces to exorcise the spell the ad cast upon him, was eventually compelled to respond directly to the summons by composing Dora Bruder. Modiano tries to retrieve fragments of the adolescent Dora's past and rescue her from oblivion, but his efforts prove largely futile, for there is no memory to retrieve. His insistence on Dora's decision to remain in Drancy with her father makes it possible for him to forgive his own father's failings and acknowledge his admiration both for him and all those who defied Occupation hypocrisy. Lastly, Modiano's text calls upon us as readers to become the guardians of the pleas that French authorities ignored and thereby accept the summons of the immemorial ourselves.
Emergent Human Pathogen Simian Virus 40 and Its Role in Cancer
Authors: Vilchez Regis A. , Butel Janet S. 
Published: July 2004

SUMMARYThe polyomavirus simian virus 40 (SV40) is a known oncogenic DNA virus which induces primary brain and bone cancers, malignant mesothelioma, and lymphomas in laboratory animals. Persuasive evidence now indicates that SV40 is causing infections in humans today and represents an emerging pathogen. A meta-analysis of molecular, pathological, and clinical data from 1,793 cancer patients indicates that there is a significant excess risk of SV40 associated with human primary brain cancers, primary bone cancers, malignant mesothelioma, and non-Hodgkin's lymphoma. Experimental data strongly suggest that SV40 may be functionally important in the development of some of those human malignancies. Therefore, the major types of tumors induced by SV40 in laboratory animals are the same as those human malignancies found to contain SV40 markers. The Institute of Medicine recently concluded that “the biological evidence is of moderate strength that SV40 exposure could lead to cancer in humans under natural conditions.” This review analyzes the accumulating data that indicate that SV40 is a pathogen which has a possible etiologic role in human malignancies. Future research directions are considered.
Pathogenesis of Malaria and Clinically Similar Conditions
Authors: Clark Ian A. , Alleva Lisa M. , Mills Alison C. , Cowden William B. 
Published: July 2004

SUMMARYThere is now wide acceptance of the concept that the similarity between many acute infectious diseases, be they viral, bacterial, or parasitic in origin, is caused by the overproduction of inflammatory cytokines initiated when the organism interacts with the innate immune system. This is also true of certain noninfectious states, such as the tissue injury syndromes. This review discusses the historical origins of these ideas, which began with tumor necrosis factor (TNF) and spread from their origins in malaria research to other fields. As well the more established proinflammatory mediators, such as TNF, interleukin-1, and lymphotoxin, the roles of nitric oxide and carbon monoxide, which are chiefly inhibitory, are discussed. The established and potential roles of two more recently recognized contributors, overactivity of the enzyme poly(ADP-ribose) polymerase 1 (PARP-1) and the escape of high-mobility-group box 1 (HMGB1) protein from its normal location into the circulation, are also put in context. The pathogenesis of the disease caused by falciparum malaria is then considered in the light of what has been learned about the roles of these mediators in these other diseases, as well as in malaria itself.
Clonorchiasis and Cholangiocarcinoma: Etiologic Relationship and Imaging Diagnosis
Authors: Choi Byung Ihn , Han Joon Koo , Hong Sung Tae , Lee Kyoung Ho 
Published: July 2004

SUMMARY
Despite a gradual decrease in prevalence, clonorchiasis is still prevalent in East Asia. A large and compelling body of evidence links clonorchiasis and cholangiocarcinoma, although the mechanisms involved are not completely understood. Clonorchiasis induces biliary epithelial hyperplasia and metaplasia, and this could facilitate at least one stage of the carcinogenesis, which is promoting effect. In areas of endemic infection, more clonorchiasis cases are now diagnosed incidentally during radiological examinations such as cholangiography, ultrasonography, and computed tomography. Radiological findings are regarded as pathognomonic for clonorchiasis since they reflect the unique pathological changes of this disorder. These radiological examinations currently play important roles in the diagnosis, staging, and decision-making process involved in the treatment of cholangiocarcinoma. The morphological features and radiological findings of clonorchiasis-associated cholangiocarcinoma are essentially combinations of the findings for the two diseases. The morphological features of clonorchiasis- associated cholangiocarcinoma, observed in radiological examinations, do not differ from those of the usual cholangiocarcinoma. In patients diagnosed with or suspected to have clonorchiasis, radiological findings should be carefully scrutinized for occult cholangiocarcinoma.
Emerging from Obscurity: Biological, Clinical, and Diagnostic Aspects of
Dientamoeba fragilis
Authors: Johnson Eugene H. , Windsor Jeffrey J. , Clark C. Graham 
Published: July 2004

SUMMARY

Ever since its first description in 1918,
Dientamoeba fragilis
has struggled to gain recognition as a significant pathogen. There is little justification for this neglect, however, since there exists a growing body of case reports from numerous countries around the world that have linked this protozoal parasite to clinical manifestations such as diarrhea, abdominal pain, flatulence, and anorexia. A number of studies have even incriminated
D. fragilis
as a cause of irritable bowel syndrome, allergic colitis, and diarrhea in human immunodeficiency virus patients. Although
D. fragilis
is most commonly identified using permanently stained fecal smears, recent advances in culturing techniques are simplifying as well as improving the ability of investigators to detect this organism. However, there are limitations in the use of cultures since they cannot be performed on fecal samples that have been fixed. Significant progress has been made in the biological classification of this organism, which originally was described as an ameba. Analyses of small-subunit rRNA gene sequences have clearly demonstrated its close relationship to
Histomonas
, and it is now known to be a trichomonad. How the organism is transmitted remains a mystery, although there is some evidence that
D. fragilis
might be transmitted via the ova of the pinworm,
Enterobius vermicularis
. Also, it remains to be answered whether the two distinct genotypes of
D. fragilis
recently identified represent organisms with differing virulence.