bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimation Uncertainty and the Equity Premium*
Authors: YAN HONG
Published: August 2009

This paper studies a dynamic equilibrium model of asset prices in a partially observable exchange economy. It shows that the precautionary savings motive in response to estimation uncertainty can dominate the risk aversion effect, resulting in the reduction of the equity premium over short horizons. This exacerbates the equity premium puzzle. Over longer holding horizons, however, estimation uncertainty does induce higher risk premiums on equity over risk‐free coupon bonds of matching maturities, as long‐term bond yields are lowered due to the precautionary savings effect.
Short Rate Dynamics and Regime Shifts*
Authors: LI HAITAO , XU YUEWU
Published: August 2009

We characterize the dynamics of the US short‐term interest rate using a Markov regime‐switching model. Using a test developed by Garcia, we show that there are two regimes in the data: In one regime, the short rate behaves like a random walk with low volatility; in another regime, it exhibits strong mean reversion and high volatility. In our model, the sensitivity of interest rate volatility to the level of interest rate is much lower than what is commonly found in the literature. We also show that the findings of nonlinear drift in Aït‐Sahalia and Stanton, using nonparametric methods, are consistent with our regime‐switching model.
Rapid Na, Cu exchange between synthetic fluid inclusions and external aqueous solutions: evidence from LA‐ICP‐MS analysis
Authors: LI Y. , AUDÉTAT A. , LERCHBAUMER L. , XIONG X. L.
Published: August 2009

Three sets of equilibration experiments (Set 1 to Set 3) were performed in cold‐seal pressure vessels to investigate the compositional modification of quartz‐hosted fluid inclusions after entrapment. Each set of experiment consisted of two stages. In a pre‐run, fluid inclusions containing 5–10 wt% NaCl and selected trace elements were synthesized at 700°C/140–200 MPa. These samples were then loaded into new capsules together with Cu‐bearing solutions and some mineral buffers, and re‐equilibrated at 600–800°C and 70–140 MPa for 6–8 days. LA‐ICP‐MS analysis of individual fluid inclusions reveals that in re‐equilibration experiments in which the outer fluid was composed of KCl (±FeCl2) up to 83% of the original Na content of pre‐existing fluid inclusions were lost, and up to 5660 ppm Cu were gained. Other elements with larger ionic radii (i.e. K, Fe, Ba, Sr) were not exchanged, demonstrating that the inclusions remained physically intact and that Na and Cu were transported through quartz by diffusion. The observed Na loss from pre‐existing fluid inclusions correlates positively with Cu gain, with about 1 Cu atom being gained per 10 Na atoms lost. Thus, Na and Cu (plus probably H) were exchanged by interdiffusion. Remarkably, this processes resulted in up to 10 times higher Cu concentrations in re‐equilibrated inclusions than were present in the outer fluid, i.e. Cu diffused ‘uphill’. Large variations of Cu concentrations relative to the concentration of other elements are common also in natural fluid inclusion assemblages. However, no evidence for a correlation between Cu content and Na content was found so far, suggesting that Cu diffusion in natural samples may be dominated by processes other than Na–Cu interdiffusion.
Hydrogeochemical modelling of CO2 equilibria and mass transfer induced by organic–inorganic interactions in siliciclastic petroleum reservoirs
Authors: Van BERK W. , SCHULZ H.‐M. , FU Y.
Published: August 2009

Different feldspar types control complex hydrogeochemical processes in hydrocarbon‐bearing siliciclastic reservoirs, which have undergone different degrees of degradation. To test such processes generically, carbon dioxide equilibria and mass transfers induced by organic–inorganic interactions have been modelled for different hydrogeochemical scenarios. The approach is based on and compared with data from the Norwegian continental shelf (Smith & Ehrenberg 1989) and assumes local thermodynamic equilibrium among solids and fluids. Equilibrating mineral assemblages (different feldspar types, quartz, kaolinite, calcite) are based on the primary reservoir composition. Equilibration and coupled mass transfer were triggered by the addition and reaction of different amounts of CO2, CH4 and H2 (plus acetic acid) at temperatures between 50 and 95°C (323 and 368 K). These components occur in oil fields as products of anaerobic bacterial degradation, hydrolytic disproportionation of hydrocarbons and/or thermal maturation of kerogen. We apply two different computer codes and two different thermodynamic data bases to calculate the results. Reaction of 0.32–0.6 mol CO2, 0.16–0.3 mol CH4 and 0.8–1.5 mol H2 with K‐feldspar, quartz, kaolinite and calcite in 1 l of pore water results in modelled values of 0.3–2.3 mol% CO2 in a multicomponent gas phase that resembles measured data (0.2–1.5 mol%). Similar CO2 contents result from acetic acid addition (CO2, CH4, H2 + 0.016 mol CH3COOH). Equilibration with albite or anorthite reduces the release of CO2 into the multicomponent gas phase dramatically, by 1 or 4 orders of magnitude compared with the equilibration with K‐feldspar. Minor differences in the modelled CO2 content (0.1–0.2 mol%) result from calculations with different computer codes if the same thermodynamic data base is applied. Relevant differences (up to 1.9 mol% CO2) result from calculations using different thermodynamic data bases.
Mechanisms of strain‐rate‐ and reaction‐dependent permeability in the mid‐crust of the Southern Alps: insight from three‐dimensional mechanical models
Authors: UPTON P. , CRAW D.
Published: August 2009

We used three‐dimensional mechanical modelling to explore the interplay of rheology, modes of permeability creation and fluid flow in the mid‐crust of an oblique orogen. We used the central Southern Alps and the Otago Schist of New Zealand to constrain our models. We also compared our models with the magnetotelluric survey along the Rangitata–Whataroa rivers that imaged a U‐shaped zone of high conductivity, interpreted as interconnected fluids, beneath the central Southern Alps. Modelling was carried out using the numerical code FLAC3D. We used a number of simple assumptions: an initially homogeneous starting material, deformation boundary conditions based on the tectonics of the South Island, the capability of the modelled material to develop an anisotropic permeability structure, strain rate and reaction‐induced permeability increases, initial saturation and lithostatic pore pressures as a basis for our models. The initial isotropic permeability was 10−18 m2. We modelled two possible mechanisms of permeability increase: (i) strain‐rate dependent and (ii) reaction dependent. For a strong mid‐crust, the models showed enhanced permeability and hence fluid interconnectivity in a symmetric region beneath the model main divide, both ends were turned up towards the brittle–ductile transition and fluid flow was the greatest in the across strike direction. For a weak mid‐crust, the region of enhanced permeability was asymmetric and turned up towards the brittle–ductile regime close to the Alpine Fault. The strong mid‐crust model reproduces the features that are common to all interpretations of the MT soundings and is our preferred model for the central Southern Alps.
Has International Trade in Saving Improved US Economic Welfare?
Authors: MAKIN ANTHONY J. , NARAYAN PARESH KUMAR
Published: August 2009

Over the past decade international policy‐makers have perceived the current account deficit of the world’s largest foreign borrower economy, the United States, as a threat to global economic and financial stability. Yet, by bridging the US domestic saving‐investment gap, capital inflow that matched the huge US current account deficit also enabled a faster rate of domestic capital accumulation than home saving alone would have permitted. Consistent with the theory of international capital movements, this study identifies and compares the respective contributions of domestic and foreign saving to US gross domestic product per worker over the two decades prior to the onset of the US banking crisis. By revealing that foreign borrowing contributed significantly to raising US output and hence living standards over this period, it adds a new dimension to the debate about global imbalances.
The Financial Sector and Economic Growth*
Authors: COORAY ARUSHA
Published: August 2009

The Mankiw–Romer–Weil (1992) augmented Solow–Swan (Solow 1956; Swan 1956) model is extended to incorporate the financial sector in this study. Distinguishing between financial capital, physical capital and human capital, the research attempts to identify, in particular, the effects of financial capital on economic growth. The effects of financial sector efficiency on economic growth are also examined. The financial sector augmented model is tested on a cross‐section of 35 economies. Strong support is found for the model.
Contributions of Longitudinal Data to Poverty Measurement in Australia*
Authors: RODGERS JOAN R. , RODGERS JOHN L.
Published: August 2009

Chronic poverty is of greater social consequence than transitory poverty but its measurement requires longitudinal data. This article uses six waves of data from the Household, Income and Labour Dynamics in Australia Survey to explore the extent to which longitudinal data contribute to what is known about poverty from cross‐section data. We find an imperfect correspondence between people’s annual poverty status and chronic poverty status. Consequently, policies that aim to reduce chronic poverty using means‐tested benefits may be partially misdirected if beneficiaries are identified using annual income. Furthermore, some households experiencing chronic poverty may fall through the safety net.
Improving Work Incentives and Incomes for Parents: The National and Geographic Impact of Liberalising the Family Tax Benefit Income Test*
Authors: HARDING ANN , VU QUOC NGU , TANTON ROBERT , VIDYATTAMA YOGI
Published: August 2009

The effective tax rates and possible work disincentives created by Australia’s tax and welfare systems have been receiving extensive policy attention in recent years. Family Tax Benefit‐Part A (FTB‐A) is one of the key causes of high effective marginal tax rates for many families. This study uses national and spatial microsimulation models to evaluate the national and local impacts of a possible FTB‐A reform option, which involves reducing the income test withdrawal rate associated with the FTB‐A income test. The modelling suggests that the option would be an effective way to reduce high effective marginal tax rates for around 415,000 parents of FTB‐A children, would benefit around 850,000 families, and would deliver additional assistance to middle income families living on the outskirts of our cities.
Role of protein kinase C in functional selectivity for desensitization at the µ‐opioid receptor: from pharmacological curiosity to therapeutic potential
Authors: Ingram Susan L , Traynor John R
Published: August 2009

Opioid agonists are the best therapy for moderate to severe pain, but clinical use is limited due to the development of tolerance and dependence. For the first time, Bailey and co‐workers have demonstrated functional selectivity for agonist‐induced desensitization of µ‐opioid receptors (MOR) in mature rat locus coeruleus neurons. Native MORs are differentially desensitized through separate, agonist‐dependent signalling pathways; desensitization of the morphine‐occupied receptor occurs via a protein kinase C alpha‐dependent pathway while [D‐Ala2, N‐MePhe4, Gly‐ol]enkephalin‐mediated desensitization is via a G protein receptor kinase subtype 2‐dependent mechanism. These results suggest that MORs adopt separate conformational states that either result in different efficiencies of G protein activation or access to phosphorylation by desensitization machinery (e.g. protein kinase C alpha or G protein receptor kinase subtype 2). Further study of the interaction of protein kinase C with MORs in native neurons will enhance our understanding of agonist‐induced functional selectivity for desensitization at MORs and provide important insights into how to selectively modulate agonist efficacy to enhance therapeutic capabilities of opioid drugs.
Chronic adrenaline treatment fails to down‐regulate the Del301–303‐α2B‐adrenoceptor in neuronal cells
Authors: Salim S , Desai AN , Taneja M , Eikenburg DC
Published: August 2009

Background and purpose:  A polymorphism of the human α2B‐adrenoceptor (Del301–303‐α2B‐adrenoceptor) has been described, and this receptor exhibits reduced G‐protein‐coupled receptor kinase (GRK) phosphorylation and impaired short‐term desensitization. Expression of the Del301–303‐α2B‐adrenoceptor also is associated with an increased risk for myocardial infarction in humans. Recent evidence from our laboratory suggests a quantitative relationship between cellular GRK3 expression levels and the sensitivity of the α2B‐adrenoceptor to agonist‐induced down‐regulation. Therefore, the present study was undertaken to study agonist‐induced down‐regulation of the wild‐type (WT)‐ and Del301–303‐α2B‐adrenoceptor in a neuronal cell model.

Experimental approach:  Haemagglutinin (HA) epitope‐tagged WT‐ and Del301–303‐α2B‐adrenoceptor containing plasmids were constructed and the receptors were stably or transiently transfected in neuroblastoma/glioma hybrid NG108 cells. The expression levels in stable transfects were ∼50 fmol·mg−1. These cells were used to examine agonist‐induced down‐regulation and phosphorylation of the WT‐ and Del301–303‐α2B‐adrenoceptor.

Key results:  The Del301–303‐α2B‐adrenoceptor, compared with the WT‐α2B‐adrenoceptor, displayed reduced adrenaline‐stimulated (20 µM) phosphorylation and did not down‐regulate in response to adrenaline (20–1000 µM). Using immunofluorescence labelling, we observed that transiently transfected WT‐α2B‐adrenoceptors internalized upon adrenaline treatment whereas the Del301–303‐α2B‐adrenoceptor did not. Finally, we determined the effect of adrenaline on the Del301–303‐α2B‐adrenoceptor in cells stably over‐expressing GRK3 3‐fold. In spite of the GRK3 over‐expression, 20–1000 µM ADR failed to down‐regulate or to increase phosphorylation of the Del301–303‐α2B‐adrenoceptor in these cells.

Conclusions and implications:  The results suggest that the 301–303 deletion mutation of the α2B‐adrenoceptor eliminates agonist‐induced down‐regulation, an effect that cannot be overcome by increasing agonist concentration or by modest GRK3 over‐expression.
Cross‐regulation between β1‐ and β3‐adrenoceptors following chronic β‐adrenergic stimulation in neonatal rat cardiomyocytes
Authors: Ufer Christoph , Germack Renée
Published: August 2009

Background and purpose: We have previously shown that β‐adrenoceptors continuously stimulated with noradrenaline induces an increase in β3‐adrenoceptors (GαiPCRs) and a decrease in β1‐adrenoceptors (GαsPCRs) at functional, genomic and protein levels. This compensatory modification induced by noradrenaline is probably one of the consequences of cardiac depression observed in heart disease. Therefore, we investigated further the interaction between β1‐ and β3‐adrenoceptors in neonatal rat cardiomyocytes.

Experimental approach: Functional studies were performed by cyclic adenosine monophosphate (cAMP) accumulation assays in cells untreated or treated with dobutamine and ICI 118551 (β1‐adrenoceptor) or CL‐3162436243 (β3‐adrenoceptor) for 24 h in the presence or absence of protein kinase inhibitors. β‐adrenoceptor and protein kinase expression was monitored by quantitative reverse transcription‐polymerase chain reaction (RT‐PCR) and by Western blotting, respectively.

Key results: Chronic β1‐ or β3‐adrenoceptor stimulation reduced β1‐adrenoceptor‐mediated cAMP accumulation in association with a decrease in β1‐adrenoceptor mRNA and protein levels through protein kinase C (PKC), phosphoinositide 3‐kinase (PI3K) and p38 mitogen‐activated protein kinase (p38MAPK) activation. In contrast, both treatments induced an increase in β3‐adrenoceptor expression and β3‐adrenoceptor‐inhibited forskolin response through PKC, extracellular‐signal‐regulated kinases 1 and 2 (ERK1/2) and p38MAPK phosphorylation, although no β3‐adrenoceptor response was observed in untreated cells. ERK1/2 and p38MAPK were activated by both treatments. The modulation of β1‐ or β3‐adrenoceptor function did not require stress‐activated protein kinase/c‐Jun N‐terminal kinase (SAPK/JNK) although chronic β1‐adrenoceptor stimulation activated SAPK/JNK. β3‐adrenoceptor treatment activated Akt although PI3K was not involved in β3‐adrenoceptor up‐regulation.

Conclusion and implications: We show for the first time that chronic β1‐ or β3‐adrenoceptor stimulation leads to the modulation of β1‐ and β3‐adrenoceptors by a cross‐regulation involving PKC, PI3K p38MAPK and MEK/ERK1/2 pathway, and through protein kinase A when β1‐adrenoceptors are chronically activated.
Novel antagonists for proteinase‐activated receptor 2: inhibition of cellular and vascular responsesin vitroandin vivo
Authors: Kanke T , Kabeya M , Kubo S , Kondo S , Yasuoka K , Tagashira J , Ishiwata H , Saka M , Furuyama T , Nishiyama T , Doi T , Hattori Y , Kawabata A , Cunningham MR , Plevin R
Published: August 2009

Background and purpose: Proteinase‐activated receptor 2 (PAR2) is a G‐protein coupled receptor associated with many pathophysiological functions. To date, the development of PAR2antagonists has been limited. Here, we identify a number of novel peptide‐mimetic PAR2antagonists and demonstrate inhibitory effects on PAR2‐mediated intracellular signalling pathways and vascular responses.

Experimental approach: The peptide‐mimetic compound library based on the structures of PAR2agonist peptides were screened for inhibition of PAR2‐induced calcium mobilisation in human keratinocytes. Representative compounds were further evaluated by radioligand binding and inhibition of NFκB transcriptional activity and IL‐8 production. The vascular effects of the antagonists were assessed usingin vitroandin vivomodels.

Key results: Two compounds, K‐12940 and K‐14585, significantly reduced SLIGKV‐induced Ca2+mobilisation in primary human keratinocytes. Both K‐12940 and K‐14585 exhibited competitive inhibition for the binding of a high‐affinity radiolabelled PAR2‐ligand, [3H]‐2‐furoyl‐LIGRL‐NH2, to human PAR2with Kivalues of 1.94 and 0.627 µM respectively. NFκB reporter activity and IL‐8 production were also significantly reduced. Furthermore, relaxation of rat‐isolated aorta induced by SLIGRL‐NH2was inhibited competitively by K‐14585. K‐14585 also significantly lowered plasma extravasation in the dorsal skin of guinea pigs and reduced salivation in mice.

Conclusions and implications: K‐12940 and K‐14585 antagonized PAR2competitively, resulting in inhibition of PAR2‐mediated signalling and physiological responses bothin vitroandin vivo. These peptide‐mimetic PAR2antagonists could be useful in evaluating PAR2‐mediated biological events and might lead to a new generation of therapeutically useful antagonists.
The signal transduction cascade regulating the expression of the gap junction protein connexin43 by β‐adrenoceptors
Authors: Salameh A , Krautblatter S , Karl S , Blanke K , Gomez D Rojas , Dhein S , Pfeiffer D , Janousek J
Published: August 2009

Background and purpose:  In mammalian heart, connexin43 (Cx43) represents the predominant connexin in the working myocardium. As the β‐adrenoceptor is involved in many cardiac diseases, we wanted to clarify the pathway by which β‐adrenoceptor stimulation may control Cx43 expression.

Experimental approach:  Cultured neonatal rat cardiomyocytes were stimulated with isoprenaline. Cx43 expression as well as activation of p38 mitogen‐activated protein kinase (MAPK), p42/44 MAPK, JUN NH2‐terminal kinase (JNK) and nuclear translocation of the transcription factors activator protein 1 (AP1) and CRE‐binding protein (CREB) were investigated. Additionally, we assessed Cx43 expression and distribution in left ventricular biopsies from patients without any significant heart disease, and from patients with either congestive heart failure [dilated cardiomyopathy (DCM)] or hypertrophic cardiomyopathy (HCM).

Key results:  Isoprenaline exposure caused about twofold up‐regulation of Cx43 protein with a pEC50 of 7.92 ± 0.11, which was inhibited by propranolol, SB203580 (4‐(4‐fluorophenyl)‐2‐(4‐methylsulphinylphenyl)‐5‐(4‐pyridyl)‐1H‐imidazole) (p38 inhibitor), PD98059 2‐(2‐amino‐3‐methoxyphenyl)‐4H‐1‐benzopyran‐4‐one) (MAPK 1 kinase inhibitor) (Alexis Biochemicals, San Diego, CA, USA) or cyclosporin A. Similar findings were obtained for Cx43 mRNA. Furthermore, Cx43 up‐regulation was accompanied by phosphorylation of p38, p42/44 and JNK, and by translocation of AP1 and CREB to the nucleus. Analysis of Cx43 protein and mRNA in ventricular biopsies revealed that in patients with DCM, Cx43 content was significantly lower, and in patients with HCM, Cx43 content was significantly higher, relative to patients without any cardiomyopathy. More importantly, Cx43 distribution also changed with more Cx43 being localized at the lateral border of the cardiomyocytes.

Conclusion and implication:  β‐adrenoceptor stimulation up‐regulated cardiac Cx43 expression via a protein kinase A and MAPK‐regulated pathway, possibly involving AP1 and CREB. Cardiomyopathy altered Cx43 expression and distribution.
Helicobacters and Extragastric Diseases
Authors: Pellicano Rinaldo , Franceschi Francesco , Saracco Giorgio , Fagoonee Sharmila , Roccarina Davide , Gasbarrini Antonio
Published: August 2009

For two decades, Helicobacter pylori has been considered as the culprit in many extragastric manifestations. However, for several of these supposed associations the hypothesis of an etiological role has not yet been fully investigated. This may be due to a series of factors linked to the epidemiological features of the studies and to the diseases investigated. This review attempts to highlight the main reported associations of H. pylori with extragastric manifestations during the last year. The most convincing data arise in the field of idiopathic thrombocytopenic purpura (ITP) and sideropenic anemia. Long‐term follow‐up studies have shown that 50% of subjects with ITP maintain a hematological response after H. pylori eradication. There is also growing evidence of the role of H. pylori in other diseases, including ischemic heart disease even though results are not conclusive.
Helicobacter spp. Other Than Helicobacter pylori
Authors: Okoli Arinze S. , Menard Armelle , Mendz George L.
Published: August 2009

Non‐H. pyloriHelicobacter species (NHPHS) are associated with several important human and animal diseases. In the past year research into this group of bacteria has continued to gain attention, and novel species have been described in new niches owing to improvements in detection methods. Polymerase chain reaction and/or sequencing remain the gold standard for the detection of this genus. New insights into the pathogenesis of the NHPHS in hepatobiliary, gastric, and intestinal diseases were gained. In particular, data revealed interaction between hepatic steatosis and infectious hepatitis in the development of hepatocellular carcinoma. Evidence of an association between hepatitis C virus and Helicobacter spp. in hepatocarcinoma development was also provided; and male sex hormone signaling appeared to influence infectious hepatitis induced by Helicobacter hepaticus. More findings support an association between Helicobacter heilmannii and gastric adenocarcinoma; and in mice, mucins MUC4 and MUC5 but not MUC1 influence the colonization and pathogenesis of Helicobacter felis. Data indicated that the roles of the adaptive immune system in H. hepaticus‐induced intestinal tumorigenesis are different in the small and large intestines, and environmental factors, such as bile acids may modulate H. hepaticus carcinogenic potential. New reports in the prevention and eradication of NHPHS showed a protective response against Helicobacter suis induced by vaccine administration, and a successful cross‐foster rederivation method successfully eradicated Helicobacter spp. from contaminated mice litters. Overall, the studies provided insights into the pathophysiology of Helicobacter species other than Helicobacter pylori.
Pathogenesis of Helicobacter pylori Infection
Authors: Costa Ana C , Figueiredo Ceu , Touati Eliette
Published: August 2009

Helicobacter pylori induces chronic inflammation of the gastric mucosa, but only a proportion of infected individuals develop peptic ulcer disease or gastric carcinoma. Reasons underlying these observations include differences in bacterial pathogenicity as well as in host susceptibility. Numerous studies published in the last year provided new insight into H. pylori virulence factors, their interaction with the host and consequences in pathogenesis. These include the role of bacterial genetic diversity in host colonization and persistence, outer membrane proteins and modulation of adhesin expression, new aspects of VacA functions, and CagA and its phosphorylation‐dependent and ‐independent cellular effects. This article will also review the recent novel findings on the interactions of H. pylori with diverse host epithelial signaling pathways and events involved in the initiation of carcinogenesis, including genetic instability and dysregulation of DNA repair.
Diagnosis of Helicobacter pylori Infection
Authors: Monteiro Lurdes , Oleastro Mónica , Lehours Philippe , Mégraud Francis
Published: August 2009

The articles published this last year in the field of Helicobacter pylori diagnosis reported the development of in vivo histology, small improvements in some invasive methods (urease test, culture, and histology) and new kits for the stool antigen tests. They also contributed to increasing our knowledge, by further exploration into specific conditions for the urea breath test and into the significance of cagA antibodies. The role of serum markers of atrophy was also confirmed. Molecular methods are still being developed for direct genotyping, detection of H. pylori and its clarithromycin resistance, either by polymerase chain reaction or fluorescent in‐situ hybridization. For the first time, there was a report on a possible interest of magnetic resonance spectroscopy.
Verbal and Visual Selective Reminding Procedures in Patients with Temporal Lobe Epilepsy
Authors: Funakoshi Akihiro , Matsumoto Izumi , Inoue Yushi , Yagi Kazuichi
Published: August 2009

Purpose: The verbal and visual Selective Reminding Procedures (SRP) of Buschke (1974) were performed in patients with temporal lobe epilepsy (TLE) to examine their usefulness for determining the laterality of the seizure focus.

Methods: The subjects were 59 (33 male and 26 female) patients with TLE. Their mean age at testing was 28.2 years (range, 15–55 years); their age at seizure onset was 11.3 years (range, 1–34 years); and their full‐scale IQ with the WAIS‐R was 79.3 (range, 52–119). The laterality of the seizure focus was determined by a preoperative workup and verified by the postoperative course for >1 year (seizure reduction to <10%). The focus was on the left side in 33 patients (group L) and on the right in 26 patients (group R). Demographic features were similar between groups L and R. All patients had left hemisphere language dominance as determined by the Wada test. Verbal SRP and visual SRP were performed preoperatively. The verbal SRP consisted of 12 unrelated nouns with three to four syllables, and the visual SRP consisted of 12 figures collected from the Rey Visual Learning Test. Performances on the verbal SRP and visual SRP were compared between groups L and R. Fisher's test, the Mann‐Whitney U test, and an unpaired t test were used for statistical analyses.

Results: Most patients of groups L and R immediately recalled five to seven stimuli on the first trial of both SRPs. On the verbal SRP, significantly more patients in group R (25 patients, 96%) recalled the 12 stimuli on two consecutive trials than those in group L (23 patients, 70%; p < 0.01), whereas the results for both groups on the visual SRP were similar (group L: 16 patients, 61%; group R: 20 patients, 62%). The number of trials before recalling the 12 stimuli without intervening reminding was similar in both groups (6.9 ± 2.24 trials in group L; 5.9 ± 2.31 in group R) on the verbal SRP, but group R needed significantly more trials (8.0 ± 2.28 trials) than group L (5.7 ± 1.89 trials) on the visual SRP (p < 0.01). On three consecutive trials, the 12 stimuli were recalled by 10 (30%) patients of group L and by 11 (42%) patients of group R on the verbal SRP, but on the visual SRP by 14 (42%) patients of Group L and by only four (15%) patients of group R (p < 0.05). The number of intrusion errors were 2.4 ± 3.60 in group L and 1.4 ± 3.80 in group R on the verbal SRP, but 16.2 ± 17.6 in group L and as much as 25.9 ± 15.8 in group R on the visual SRP (p < 0.05).

Conclusions: Group L showed difficulty in storing verbal stimuli compared with group R. On the other hand, group R was more impaired in the effective storage and retrieval of visual stimuli than was group L. Verbal and visual SRPs may help to determine the laterality of the seizure focus in patients with TLE.
Transinferior Temporal Amygdalohippocampectomy for Temporal Lobe Epilepsy
Authors: Takeuchi Juji , Kubo Hiroaki , Kawasaki Jun , Kanemoto Kousuke
Published: August 2009

Purpose: We describe a new surgical approach for removing the amygdalohippocampal complex. This approach does not require difficult surgical techniques, has had no complications so far, and the operative results have been excellent for obtaining sufficient seizure control.

Methods: After a temporal craniotomy, the inferior temporal gyrus is exposed. A cortical incision, 15 nun superior and parallel to the temporal base, from the temporal tip to 50 mm (left side) or 60 mm (right side) posterior to it is made. The incision is deepened to reach to the arachnoid near the tentorial edge. When this is accomplished, the inferior temporal horn is opened widely, and the entire hippocampus is exposed. The hippocampus, as well as the parahippocampal gyrus, is removed in two pieces of ∼2 cm long each. The inferior half of the amygdala and the temporal basal cortex just in front of the head of hippocampus is also removed.

Results: Of the 30 operated on cases that were followed up for > 1 year, 25 were completely seizure free, two had only a few auras a year, two had a few complex partial seizures a year, and one showed no change. This distribution is quite satisfactory.

Conclusion: This approach is easy, but the results are satisfactory. Of course, the anterior temporal approach is the standard technique; however, the novel approach should be considered, especially when the entire hippocampus is to be removed.
Callosotomy in Children: Experience in the Veterans General Hospital‐Taipei
Authors: Wong Tai‐Tong , Chang Kai‐Ping , Kwan Shang‐Yeong , Chi Ching‐Shiang , Yang Tsui‐Fen , Lee Ying‐Chiao , Guo Wan‐Yuo
Published: August 2009

Purpose: Surgery is becoming more important for the treatment of chronic seizures in the pediatric age group. Common surgical procedures in children include anterior callosotomy and resection of focal lesions and surrounding tissue.

Methods: The underlying diseases or pathologies for the chronic seizures of children included cryptogenic epilepsy, tumors, vascular lesions, dysplasia, and posttraumatic or ischemic events. Anterior callosotomy was performed, mainly for Lennox‐Gastaut syndrome. Patients with intractable secondarily generalized or generalized seizures were referred to the Hospital and selected for presurgical evaluation. Until 1996, 82 callosotomies had been performed. The surgical technique consisted of dissecting and splitting the anterior two thirds to four fifths of the corpus callosum through a frontal interhemispheric approach. Intraoperative precallosotomy and postcallosotomy electrocorticography (ECoG) studies were performed.

Results: The mean age at the time of the operation was 8 years. The mean duration of the seizures was 5.3 years. There was no operative mortality or significant neurologic complications. With a mean follow‐up period of 1.9 years, the outcome was that 20.7% of the children were seizure free, and 41.5% showed a significant improvement.

Conclusions: Sixty‐three percent of the parents were satisfied with the results. Some children showed an improvement in their hyperactivity, attention span, and social skills. However, there was no help for their mental retardation.
Two Patients with Angelman Syndrome Followed Beyond 20 Years of Age
Authors: Koide Hiroyoshi , Kaneko Atushi , Miyazaki Hiromi , Yokoyama Yasuko , Kurata Midori
Published: August 2009

Purpose: Angelman syndrome is now diagnosed appropriately because of the development of the fluorescence in situ hybridization (FISH) method. We encountered two cases of this syndrome, and the follow‐up studies until adulthood produced some interesting clinical findings.

Case Reports: Case 1 was a 23‐year‐old man. Albinism, delayed speech development, hyperactivity, avoidance of eye contact, and hypersalivation were noticed. Cerebral palsy ‐was suspected. He could walk independently by age 2 years but could not speak a single word. At age 3 years, epileptic seizures developed and were observed frequently until age 10 years. At that time, his condition was consistent with epilepsia partialis continua because of tremors of the left hand and a continuation of the electroencephalographic (EEG) findings of spikes on the midtemporal and right central regions. The epileptic attacks were controlled with clonazepam (CZP). A constant happy demeanor has been noticed but outbursts of laughter have not been observed. Diffuse high‐amplitude slow‐wave activity with intermittent spike‐wave discharges, which are the characteristic EEG features of Angelman syndrome, disappeared and spike‐wave‐like discharges over the frontal area were observed thereafter. The present clinical features are severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, oculocutaneous albinism, and semiopened large mouth with protruding tongue and salivation. A chromosomal analysis disclosed 46XYde1(15)(qIl.lql2), and the FISH method detected the deletion of the signal SNRNP.

Case 2 was a 20‐year‐old man. Intellectual disability and hyperactivity had been noticed since infancy. Cerebral palsy was suspected. He could walk independently by 3 years and 6 months but could not speak a single word. The initial epileptic seizure occurred at age 2 years and 7 months. However, no seizures were observed after age 9 years. He has had a constant happy demeanor but no outbursts of laughter. At the present, he shows severe intellectual disability, happy disposition, clumsy and awkward gait without palsy, hypopigmented skin color, and semiopened large mouth with protruding tongue and salivation. EEG examination during childhood revealed the characteristic EEG activities of Angelman syndrome, diffuse high‐amplitude slow waves with intermittent spikes. However, at the present, only migratory focal spikes are seen. A chromosomal analysis disclosed 46XY del(l5)(qllq13), and the FISH method revealed a deletion of the SNRNP region.

Conclusions: We followed up two patients with Angelman syndrome who were diagnosed with the FISH method. Patients with severe intellectual disability and a constant happy demeanor should be studied with the FISH method. Epileptic attacks were well controlled after adolescence, and the characteristic diffuse high‐amplitude slow‐wave activities disappeared thereafter.
Lactate and NAA Mapping Assessed by Proton NMR Chemical‐Shift Imaging in Seizures
Authors: Nakasu Yoko , Morikawa Shigehiro , Inubushi Toshiro , Handa Jyoti
Published: August 2009

Purpose: To observe metabolic maps of lactate and N‐acetyl asparate (NAA) by proton nuclear magnetic resonance (NMR) in vivo in the rat brain during the acute stage of hemispheric seizures.

Methods: Adult male Sprague‐Dawley rats were anesthetized with isoflurane and were examined by using a 2.0‐T CSI Omega system. Seizures were elicited through transient opening of the blood‐brain barrier (BBB) in the left hemisphere by injection of a hyperosmolar solution of mannitol into the left internal carotid artery, following an intravenous injection of bicuculline methiodide. Both hemispheres were then observed from an axial view before and after the induction of seizures by using the three‐dimensional chemical shift imaging (CSI) technique. Proton CSI data were obtained from a 40 × 40 mm2 FOV, divided into an 8 × 8 matrix, by using water suppression, fat suppression, and outer volume suppression, thus creating a metabolic map. The opening of the BBB was confirmed as a transient increase in signal intensity in the left hemisphere on T,‐weighted MR images.

Results: Neither the intravenous injection of bicuculline methiodide nor the transient opening of the BBB alone caused seizure activity. The rats developed tonic‐clonic seizures after the transient opening of the BBB after injection of bicuculline methiodide. The left hemisphere showed periodic spikes on the scalp EEG ‐15 min after the opening. Metabolic images showed an accumulation of lactate in the left cerebral hemisphere at 1 and 3 h after seizure induction. Metabolic images of lactate, however, detected no abnormalities in the hemisphere 24 h after the seizure. No clear concurrent changes in the NAA map were observed in this study. The cerebellar hemispheres showed no changes of either the lactate or NAA metabolic images.

Conclusions: We found a transient accumulation of lactate in the cerebral hemisphere due to abnormal neuronal excitation after its evocation with bicuculline methiodide. The metabolic maps were obtained in vivo with a noninvasive procedure. We suggest that lactate can be a reversible indicator for NMR metabolic mapping, showing the focus of abnormal neuronal excitation in the acute stages of clinical seizures.
The Corpus Callosum and Epileptic Seizures: Experimental Results in Cats
Authors: Yamashiro Katsumi , Tomiyama Ndoki , Ishida Akihiko , Terada Yukitoshi , Kinjo Toshihiko , Yoshii Yoshihiko , Mukawa Jiro
Published: August 2009

Purpose: Corpus callosotomy (CC) has recently been recognized as an effective treatment for patients with intractable generalized seizures. Experimental studies also reported the same seizure‐suppressive effects. We investigated the effects of sectioning the corpus callosum in models of epilepsy in cats.

Methods: Acute and subacute models of epilepsy were made by the topical application of estrogen and cobalt powder, respectively, at the left anterior sigmoid gyrus (ASG). The electrocorticogram (ECoG) and steady potentials (SPs) were recorded from both sides of the anterior sigmoid gyrus and the ventrolateral (VL) nucleus of the thalamus. The spindle‐like afterdischarges were elicited by direct stimulation of the cortex or VL nucleus of thalamus. The “surface negative (SN) wave” produced by pyramidal tract stimulation and recorded at the cortical surface has been identified as a reflection of postsynaptic potentials generated through recurrent inhibitory pathways (Humphrey et al. 1968). SN waves were analyzed for the assessment of the cortical inhibitory mechanisms before and after sectioning the corpus callosum.

Results: Topical application of estrogen to the left ASG (acute model) induced spike‐waves on both sides of the ASG and VL. The SP showed a negative shift on the same side as the estrogen application: however, no change in the SP was seen on the contralateral side. In this (acute) model, a remarkable reduction or disappearance of spike‐waves on the side contralateral to estrogen application, was seen just after the sectioning of the corpus callosum. The spindle‐like afterdischarges were also difficult to induce on the same side as estrogen application after callosal sectioning. Cobalt powder also induced spike‐waves after topical application to the left ASG (subacute model). The spindle‐like afterdischarges showed a reduction after the callosal sectioning. The SN waves gradually diminished in amplitude after topical application of cobalt powder on the same side of the ASG as the application. In the contralateral ASG, the SN waves showed a slight reduction in amplitude. These phenomena were presumably due to depression of recurrent postsynaptic inhibition caused by the topical application of the epileptogenic agents. After callosal section, the SN waves recovered in amplitude on both sides.

Conclusions: These data suggest that the corpus callosum is maintaining epileptiform activity during the advanced stages of epilepsy. They also suggest that sectioning of the corpus callosum suppress epileptic activity because of recovery of cortical inhibitory mechanisms as represented by the amplitude of the SN wave.
Dopamine Receptors and Hippocampal Seizure Generation
Authors: Minabe Yoshio , Hashimoto Kenji , Watanabe Kei‐ichiro , Nishimura Tsutomu , Ashby Charles R.
Published: August 2009

Purpose: We examined the effects of selective cyclic adenosine monophosphate (AMP) phosphodiesterase type 4 inhibitors and dopamine D1‐receptor agonists on hippocampal partial seizures induced by electrical stimulation at 2 Hz in freely moving rats. We also tested the effects of acute (single injections) and repeated (injections once per day for 21 days) administration of typical and atypical antipsychotic drugs.

Methods: We used five seizure parameters to assess the effects of the drugs [i.e., pulse number threshold (threshold for the initial primary afterdischarges), duration of the primary afterdischarge, latency of the secondary afterdischarges, duration of the secondary afterdischarges, and duration of the behavioral seizures]. The detailed methods have been described elsewhere (Katsumori et al. Eur J Pharmucol 1996;311:37–44, and Synapse 1997;27, in press).

Results: cAMP phosphodiesterase inhibitors (rolipram 1, 3, or 10 mg/kg, i.p.; RO 20–1724, 10 mg/kg, i.p.) and dopamine D,‐receptor agonists (SKF 38393, 1.5, 5, or 15 mgkg, i.p.; SKF 81297, 3 mgkg, i.p.) produced the same type of proconvulsive action, by selectively enhancing the generation of secondary afterdischarges. The dopamine D1‐receptor antagonist, SCH 23390 (0.5 mg/kg, i.p.) blocked the effect of SKF 38393 but not that of rolipram. The dopamine D1‐receptor antagonist, sulpiride (45 mg/kg, i.p.). showed no effect on the seizure parameters. A single injection of either 5 or 15 mg/kg of clozapine significantly decreased the pulse number threshold and significantly increased the duration of primary afterdischarges, indicating a proconvulsive action. The repeated administration of clozapine (1.5, 5, or 15 mg/kg, i.p.) produced dose‐dependent, proconvulsive effects by significantly decreasing the pulse number threshold and by significantly increasing the duration of primary afterdischarges. In contrast to clozapine, the short‐term administration of haloperidol (0.5 and 1.5 mg/kg, i.p.), unlike clozapine, significantly decreased the duration of primary afterdischarges, but did not alter the pulse number threshold.

Conclusions: These results suggest that the proconvulsive action of dopamine D1‐receptor stimulation is, at least partially, due to the resulting increase in cAMP levels in the brain. Clozapine produces a greater proconvulsive action than haloperidol or sulpiride in this animal model of hippocampal seizures. It remains to be determined whether modulation of the secondary afterdischarges has any predictive value for specific aspects of hippocampal epileptogenesis.
Estimation of the Epileptic Focus in Temporal Lobe Epilepsy‐ Investigation with Dipole Tracing Using a Realistic Three‐Shell Head Model
Authors: Coda Kazuo , Hoshida Tohru , Hashimoto Hiroshi , Sakaki Toshisuke
Published: August 2009

Purpose: The location of the electrical generator in the brain can be estimated with dipole tracing. We estimated the equivalent current dipole with scalp electroencephalogram (EEG) in patients with temporal lobe epilepsy by using dipole tracing, and compared the results with the epileptogenic focus identified by long‐term subdural EEG recording.

Methods: We studied five patients with temporal lobe epilepsy who underwent long‐term subdural EEG recording. Three were male and two were female patients. Their ages ranged from 18 to 65 years (mean age, 43 years). All patients had intractable seizures and were scheduled to be treated surgically. We recorded the scalp EEG with a digital EEG recorder, and then made three‐shell head models from the computed tomograms. We estimated the equivalent current dipoles with spikes and compared the results with the epileptogenic foci, which were identified with long‐term subdural EEG recording.

Results: Case 1 was a 67‐year‐old man. We estimated the equivalent current dipole in the right lateral temporal lobe with dipole tracing. The epileptogenic focus was identified with long‐term subdural EEG recording in the same region. The distance was 18 mm between the equivalent current dipole estimated with dipole tracing and the epileptogenic focus identified with long‐term subdural EEG recording. Case 2 was a 37‐year‐old man. We estimated the equivalent current dipole in the left temporal base and identified the epileptogenic focus with long‐term subdural EEG recording in the same region. The distance was 13 mm between the equivalent current dipole and the epileptogenic focus. Case 3 was a 57‐year‐old woman. We estimated the equivalent current dipole in the left temporal base and identified the epileptogenic focus with long‐term subdural EEG recording in the same region. The distance was 12 mm between the equivalent current dipole and the epileptogenic focus. Case 4 was an 18–year‐old man. We estimated the equivalent current dipole in the left temporal base and identified the epileptogenic foci in the same region. The distance was 19 mm between the equivalent current dipole and the epileptogenic focus. Case 5 was a 38‐year‐old woman. We estimated the equivalent current dipole and identified the epileptogenic focus in the same region. The distance was 8 mm between the equivalent current dipole and the epileptogenic foci. The mean distance in all cases between the equivalent current dipole and the epileptogenic foci was 14 mm.

Conclusions: The equivalent current dipole estimated by using dipole tracing of the realistic three‐shell head model with spikes from the scalp EEG was in accordance with the epileptogenic focus identified with long‐term EEG from a subdural grid. There is a close relation between the equivalent current dipole estimated by dipole tracing with spikes and the epileptogenic focus identified with subdural EEG recording.