bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuromechanism of Developing Methamphetamine Psychosis: A Neuroimaging Study
Authors: IYO MASAOMI , SEKINE YOSHIMOTO , MORI NORIO
Published: November 2004

Abstract: The long‐term use of methamphetamine (MAP) induces a psychotic state, called MAP psychosis. To understand the neuromechanisms of the persistent psychosis, we used SPECT, MR spectroscopy (MRS), and PET on the MAP users. The SPECT study showed a high incidence of multiple patchy deficits in cerebral blood flow among the users. The MRS study MAP users showed a significantly reduced ratio of creatine plus phosphocreatine (Cr + PCr)/choline‐containing compounds (Cho) in the brain compared with the healthy control subjects. In addition, the reduction in the ratio of Cr + PCr/Cho was significantly correlated with the duration of MAP use and with the severity of residual psychiatric symptoms. PET revealed no significant differences between the ex‐users of MAP and the healthy controls in the density of striatal dopamine D2 receptors. On the other hand, the density of dopamine transporter in the nucleus accumbens and caudate/putamen in the MAP users was significantly less compared with the controls. This reduction was significantly correlated with the length of use and severity of psychotic symptoms. These findings suggest that long‐term use of MAP causes abnormal cerebral blood flow patterns, reduction of brain dopamine transporter density, and metabolite alteration, which may be closely related to a susceptibility to MAP psychosis.
Repetitive Cocaine Administration Decreases Neurogenesis in Adult Rat Hippocampus
Authors: YAMAGUCHI M , SUZUKI T , SEKI T , NAMBA T , JUAN R , ARAI H , HORI T , ASADA T
Published: November 2004

Abstract: Cocaine HCl (20 mg/kg) was administered to adult male rats to investigate the effects of cocaine on neurogenesis in the hippocampus. Proliferation of granule cells in the dentate gyrus was measured by in vivo labeling with 5‐bromo‐2′‐deoxyuridine (BrdU). Rats that received repetitive cocaine treatment for 14 days showed 26% fewer BrdU‐positive cells relative to control rats, while no difference was observed in the rats that received a single injection of cocaine. Differentiation of newly born cells was not influenced. The present experiment is the first to demonstrate the influence of cocaine on hippocampal neurogenesis. These data suggest that the regulation of hippocampal neurogenesis may be involved in the emergence of certain symptoms of cocaine addiction, such as cognitive impairment and behavioral sensitization.
Recent Trends of Drug Abuse and Drug‐Associated Deaths in Korea
Authors: CHUNG HEESUN , PARK MEEJUNG , HAHN EUNYOUNG , CHOI HAEYOUNG , CHOI HWAKYUNG , LIM MIAE
Published: November 2004

Abstract: Methamphetamine is the most abused drug in Korea followed by cannabis and opiates. Recent characteristics of the drug problem in Korea include increased drug smuggling from abroad, drug trafficking by organized gangs, varieties of drug smuggling, foreigners engaged in drug smuggling, and spread among drug abusers and areas. New drugs such as MDMA, Yaba, and LSD are found in greater proportion in the seizure records, indicating diversification of smuggled drugs in Korea. In addition, there is a growing tendency for the abuse of common medicines among young people in Korea because they are easily available. Methamphetamine is so seriously abused that fatalities from its overdose have occurred; since 1985, 20 such fatalities have been reported. Many deaths from the abuse of noncontrolled substances, especially dextromethorphan, zipeprol, and carisoprodol, which are taken for their hallucinogenic effects, were also reported. Recently, there was even a fatality related to smuggling of cocaine by body‐packing.
Monitoring Drug‐Induced Neurodegeneration by Imaging of Peripheral Benzodiazepine Receptors
Authors: WEISSMAN BEN AVI , BRANDEIS RACHEL , GILAT ERAN , COHEN GIORA , ALKALAY DAVID , RABINOVITZ ISHAI , SONEGO HAGAR , RAVEH LILY
Published: November 2004

Abstract: Several drugs of abuse are known to produce an array of deleterious effects, including alterations in neuronal circuitry and, ultimately, neuronal degeneration. For instance, methamphetamine was shown to induce substantial nigrostriatal dopaminergic terminal damage, including an increase in glial fibrillary acidic protein, a marker for astrocyte proliferation. Nevertheless, there was almost no attempt to define neurodegeneration by measuring the abundance of reactive microglia. In fact, some investigators fail to differentiate between astrocytes and microglia and claim glial fibrillary acidic protein to be a marker for gliosis. To date, there are numerous methods designed to assess brain neuropathologies resulting from a wide arsenal of insults. Regardless of the cause of neuronal damage, reactive glial cells always appear at and around the site of degeneration. These cells are distinguished by the exceptional abundance of peripheral benzodiazepine receptors (PBRs; ο3 sites), particularly as compared to surrounding neurons. Measuring the binding of specific ligands to these PBRs (for example, [3H]PK 11195) offers a unique indirect marker for reliable impairment estimation in the central nervous system. Moreover, the availability of agents such as [11C]PK 11195 paved the road to in vivo animal and human brain positron emission tomography scanning, demonstrating inflammation‐like processes in several diseases. Additionally, the measurement of increased binding of PBR ligands provides a faithful indicator for the behavioral and cognitive deficits accompanying neuronal injury.
Effects of Postnatal Cocaine Exposure and Environmental Enrichment on Rat Behavior in a Forced Swim Test
Authors: MAGALHÃES ANA , SUMMAVIELLE TERESA , TAVARES MARIA AMÉLIA , de SOUSA LILIANA
Published: November 2004

Abstract: This study examined the effects of environmental enrichment on rats exposed to cocaine during the first month of life, in several categories of behavior observed in a forced swim test. Wistar rats were divided in four groups. The first included pups that were subjected to injections of cocaine hydrochloride (15 mg/kg body weight/day, subcutaneously, in two daily doses, from postnatal days 1 to 27) and reared in an enriched environment (CocEE); the second, pups that were subjected to injections of cocaine (as previously described) and reared in a standard environment (CocSE); the third, pups that were subjected to saline injections and reared in an enriched environment (SalEE); the fourth, pups that were subjected to saline injections and reared in a standard environment (SalSE). On postnatal days 26 and 27, rats were tested in a swimming pool in two 5‐min sessions. The categories of behavior studied in this work were: fast swim, slow swim, struggling, diving, and immobility. Results showed that postnatal cocaine exposure decreased the time spent on fast swim during the two sessions and increased the immobility behavior during the second session in CocSE pups compared with SalSE pups. SalEE pups increased the time spent in fast swim, slow swim, and diving, and decreased the time spent in struggling and immobility during the two sessions compared with SalSE pups. CocEE animals spent more time in fast swim and struggling and less the time in immobility compared with CocSE pups. The present results suggest that postnatal cocaine exposure affects the ability of these animals to cope with stressful situations, and that environmental enrichment seems to enable the rats to adopt a more active strategy, one that allows them to better cope with this particular stress situation.
Abnormal Immunoreactivity to Serotonin in Cerebellar Purkinje Cells after Neonatal Cocaine Exposure
Authors: SUMMAVIELLE TERESA , ALVES CECILIA J. , MONTEIRO PEDRO R.R. , TAVARES MARIA AMELIA
Published: November 2004

Abstract: Neonatal cocaine is known to affect the developing serotonergic system in many brain structures, including the cerebellum. Changes in the cerebellar Purkinje cells after drug exposure are well documented and result in impairment of movement and other cerebellar disorders such as ataxia. These cells have a major postnatal developmental pattern; therefore, neonatal exposure to cocaine is likely to affect them. In this work, male and female Wistar rats were injected with 15 mg of cocaine hydrochloride/kg body weight/day, subcutaneously, in two daily doses, from postnatal day 1 (PND1) to PND29. Controls were given 0.9% of saline. On PND14, PND21, and PND30, rats were transcardially perfused, and brains removed and cryoprotected. Coronal sections from the cerebellum were processed for immunocytochemistry of cells containing serotonin (5‐hydroxytryptamine, or 5‐HT). At the same postnatal age, rats from at least three different litters were sacrificed by decapitation, and brains were dissected for determination of 5‐HT in the cerebellum by high‐performance liquid chromatography with electrochemical detection. Upon the expected distribution of immunoreactivity to 5‐HT, an abnormal immunoreactivity to 5‐HT was observed in the Purkinje cells of six cocaine‐exposed animals, but not in control animals. Also, levels of cerebellar 5‐HT in cocaine‐exposed rats were significantly increased on PND21. These results, together with previously reported observations of altered patterns of motor behavior, indicate that neonatal cocaine exposure affects the serotonergic cerebellar system, altering the standard development of Purkinje cells and possibly compromising the motor function.
Effects of Pretransplantation Treatment With Rituximab on Outcomes of Autologous Stem-Cell Transplantation for Non-Hodgkin's Lymphoma
Authors: Hoerr Amy L. , Gao Feng , Hidalgo Josephine , Tiwari Divya , Blum Kristie A. , Mathews Vikram , Adkins Douglas R. , Blum William , Devine Steven , Vij Ravi , Goodnough Lawrence T. , Dipersio John F. , Khoury Hanna J.
Published: November 2004

Purpose

To analyze the effects of preautografting treatment with rituximab (R) on stem-cell mobilization, post-transplantation complications, engraftment, disease-free survival, and overall survival in patients with non-Hodgkin's lymphoma (NHL).

Patients and Methods

Single-institution retrospective comparative outcome analysis in a cohort of 273 relapsed chemosensitive NHL patients of whom 127 (47%) received R pretransplantation.

Results

R was administered a median of 3 months before autologous transplantation. When compared to the nonrituximab group, R patients were older (56 v 50 years; P < .001), and had delays in post-transplantation platelets recovery (39 v 27 days; P = .001). Pretransplantation R did not affect stem-cell mobilization, post-transplantation early complications, duration of hospitalization, or mortality rates at days 30 and 100. In contrast to patients with low-grade NHL, both disease-free and overall survival rates were significantly better when R was included in the pretransplantation salvage therapy for patients with intermediate-grade NHL.

Conclusion

In this large, single-center retrospective analysis, pretransplantation treatment with R was associated with improved survival in patients with intermediate-grade NHL, at the price, however, of a delay in platelet engraftment.
Wilms' Tumor in Adults: Results of the Society of Pediatric Oncology (SIOP) 93-01/Society for Pediatric Oncology and Hematology (GPOH) Study
Authors: Reinhard Harald , Aliani Schahin , Ruebe Christian , Stöckle Michael , Leuschner Ivo , Graf Norbert
Published: November 2004

Purpose

In the Society of Pediatric Oncology (SIOP) 93-01 study, 30 patients older than 16 years were found to have Wilms' tumor. They were treated according to the pediatric protocol and were analyzed for clinical presentation, stage distribution, and prognosis.

Patients and Methods

Patient age ranged from 16 to 62 years (median, 25.4 years). Tumor stages were defined according to SIOP, and treatment was risk-adapted according to SIOP 93-01/Society for Pediatric Oncology and Hematology (GPOH) protocol. The patients were evaluated with regard to response, toxicity, and prognosis. Specimens of all tumors were centrally reviewed.

Results

Ten patients (33%) had metastatic disease at the time of diagnosis (liver, four patients; lung, three patients; liver and lung, three patients). The local stage distribution showed a predominance of higher stages (stage I, eight patients; stage IIN−, three patients; stage IIN+, four patients; stage III, 15 patients). Histologic studies revealed intermediate-risk in 23 of 30 tumors; two tumors were classified as high-risk; and three tumors were clear-cell sarcomas. Two of 30 patients showed a nephroblastoma and a renal cell carcinoma simultaneously in the same kidney. A complete remission was achieved in 24 patients; four patients relapsed after complete remission; and three of them reached a second remission with further treatment. Event-free survival was 57%, with an overall survival of 83% (median observation time, 4 years).

Conclusion

Adults can be cured in a high percentage by a multimodal treatment according to pediatric protocols. Toxicity is higher than in children, but acceptable in view of the high remission rate.
Bovine Serum Albumin-Estrogen Compounds Differentially Alter Gonadotropin-Releasing Hormone-1 Neuronal Activity
Authors: Temple Jennifer L. , Wray Susan
Published: November 2004

Steroid hormones regulate a host of physiological processes and behaviors. These actions can occur by genomic mechanisms involving gene transcription or by nongenomic mechanisms proposed to involve receptors associated with the plasma membrane. BSA-conjugated steroid hormones have been extensively used to elucidate signal transduction pathways for these hormones. We have previously shown, using calcium imaging, that 17β-estradiol (E2) significantly increases GnRH-1 neuronal activity. During the course of these experiments, it became apparent that three different BSA-estrogen compounds have been used in a variety of cell types: 17β-estradiol 6-O-carboxymethyloxime-BSA (E2-6-BSA); 1,3,5(10)-estratrien-3,16α,17β-triol-6-one 6-O-carboxymethyloxime-BSA (E-6-BSA); and 1,3,5(10)-estratrien-3,17β-diol 17-hemisuccinate-BSA (E2-17-BSA). The effects of these compounds on GnRH-1 neuronal activity were compared using calcium imaging. E-6-BSA and E2-17-BSA, but not E2-6-BSA, significantly increased all parameters of GnRH-1 neuronal activity. In addition, the effects of these two BSA compounds were reversed by the estrogen receptor antagonist ICI 182,780 but not by inhibition of gene transcription. The effects of E2-17-BSA, but not E-6-BSA were reversed by treatment with pertussis toxin, which blocks G protein-coupled receptors. These data indicate that these compounds cannot be used interchangeably and clearly have different binding properties and/or different effects on target tissues.
Serum Lipid Concentrations and Prevalence of Dyslipidemia in a Large Professional Population in Beijing
Authors: Li Zhiyan , Yang Ruifeng , Xu Guobing , Xia Tiean
Published: November 2004

Background: Lipid abnormalities are major risk factors for premature coronary artery diseases. We investigated serum lipids and the prevalence of dyslipidemia in a professional population in Beijing and compared these data with those obtained in a similar population during 1984–1986.

Methods: We studied 14 963 individuals 20–90 years of age. Health status was determined by questionnaires and physical check-ups. Total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), and total triglycerides (TGs) were measured. TC >5.7 mmol/L, LDL-C >3.6 mmol/L, TGs >1.7 mmol/L, and HDL-C <0.9 mmol/L were defined as abnormal.

Results: Mean serum TC, LDL-C, and TG concentrations were increased compared with the values obtained in 1984–1986, with 52.7% of males and 42.9% of females having at least one abnormal lipid concentration. Hypercholesterolemia occurred in 6% of males and 2.8% of females in the younger group (20–39 years) and in 20.2% of males and 38.7% of females in the older group (>60 years). HDL-C was abnormally low in ∼7% of males and in 1.6% of females. The prevalences of hypercholesterolemia, hypertriglyceridemia, and abnormally low HDL-C, especially the presence of slight hypertriglyceridemia, were higher than in 1984–1986 in all age groups. The increase was most prominent in the middle age group (40–59 years).

Conclusions: Hypercholesterolemia, hypertriglyceridemia, and abnormally low HDL-C have increased considerably over the past 20 years in professional populations in Beijing. Dietary changes and less physical activity resulting from rapid improvements in living conditions may be the causes for the increases. Enhanced preventive measures should be undertaken to modify these situations.
THE IMAGINATION GOES VISITING
Authors: NAZAR HINA
Published: November 2004

Owing to her focus on the gendered norms of propriety, Jane Austen tends to be identi�ed as a novelist of convention rather than of modernity. In this essay, however, I argue for a more �uid reading of Austen's gender politics as well as the modernity of her work, by examining the understanding of judgment that she articulates in her �rst published novel, Sense and Sensibility (1811). I place this novel in the context of an extensive discourse of critical judgment, which �ows from the Enlightenment to such theorists of the public sphere in the twentieth century as Hannah Arendt and Seyla Benhabib. In keeping with this tradition, Austen identi�es judgment to be profoundly intersubjective and, as such, compatible with those social norms that cultivate mutual recognition and dialogue. Unlike political theorists like Arendt, however, who restrict the use of judgment to the public sphere, Austen identi�es the domestic sphere to be a crucial venue for exercising this faculty. In Sense and Sensibility the domestic sphere becomes an important part of "the social," understood by Austen as the venue of intersubjective relations in addition to norms and conventions. Her reinscription, in particular, of the drawing room as a conversational space in which intersubjective agreement can be generated opens up a reading of her work as friendly to a central insight of feminist public-sphere theory-the idea that the dualism of public and private spheres withholds value from participation in public spaces that are not recognizably political spaces but that bear on the achievement of progressive political goals.
GE0RGE GISSING'S AMBIVALENT REALISM
Authors: MATZ AARON
Published: November 2004

In this essay I examine one author's peculiar struggle with the implications and expectations of realism in �ction. In late-Victorian England, George Gissing was at the epicenter of the debates about realism in the novel; for many of his contemporaries he was the archetypal writer of realist �ction. His novels seemed to rely on the grim detail and un�inching techniques associated with that school, and in his criticism he returned constantly to the question of "the place of realism in �ction" (the title of an essay he wrote in 1895). But Gissing never reached a stable verdict on the subject. In his masterpiece, New Grub Street (1891), one of his destitute writer-�gures is nicknamed "the Realist" and preaches "an absolute realism"; in the ruthless world of Gissing's modern Grub Street, the catchword is almost everywhere. What is so odd about the novel is how Gissing's portraits of aspiring realists vacillate between genuine sympathy and merciless satire. Sometimes Gissing seems to identify with those who subscribe to a platform of late-Victorian realism; at other times he appears to mock the whole ridiculous affair. New Grub Street effectively dramatizes Gissing's ambivalence about the workings and purposes of realism in the novel. In this essay I study his vexed attitude by considering New Grub Street in relation to Gissing's Augustan satirical precursors, the response to his �ction in the 1890s, and his own critical writings from the era, especially his extensive commentary on Charles Dickens.
Predicting bullying and victimization among early adolescents: Associations with disruptive behavior disorders
Authors: Kokkinos Constantinos M. , Panayiotou Georgia
Published: November 2004

Bullying is a common problem faced by children and adolescents in schools. One hypothesis that needs to be examined regarding the causation of this problem is whether being a bully or a victim may stem from disparate underlying patterns of psychopathology. Results are particularly scarce regarding the association between bully‐victim problems and disruptive behavior disorders. The present study sought to investigate the association between DSM‐IV symptoms of Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), and bully‐victim problems in a sample of 202 adolescents, aged 12–15, attending two junior high schools in Cyprus, to determine whether these symptoms differentiate between bullies and victims and provide a new approach to the understanding of bully‐victim problems. Students completed measures of bullying, victimization, disruptive behavior disorder symptoms, and self‐esteem, along with demographic questions. On the basis of their responses, teenagers were classified as bullies, victims, or both bullies and victims. Those who were bully/victims reported greater CD symptomatology. CD and low self‐esteem were predictive of bullying, whereas ODD and low self‐esteem were predictive of victimization. Aggr. Behav. 30:520–533, 2004. © 2004 Wiley‐Liss, Inc.
Criminal attitudes to violence: Development and preliminary validation of a scale for male prisoners
Authors: Polaschek Devon L.L. , Collie Rachael M. , Walkey Frank H.
Published: November 2004

Two studies report on the development and preliminary psychometric properties of a new scale measuring criminal attitudes to violence. In Study 1, the responses of a mixed sample of male prisoners were used to select 20 scale items from a larger pool. The final scale (the Criminal Attitudes to Violence Scale; CAVS) was designed so that it had a single‐factor structure and was uncorrelated with a measure of social desirability bias. It demonstrated high internal reliability, and a strong relationship to a self‐report measure of physical aggression. Significant differences were found in CAVS mean scores for various offence history comparisons, such as whether or not the offender was currently on sentence for a violent conviction. In the second study, most results from the first study were replicated with an independent sample of male prisoners. Further, compared to another scale measuring attitudes to aggression [the EXPAGG Instrumental subscale; Archer and Haigh, 1997b], the CAVS was a better predictor of general attitudes to crime. Mean CAVS scores were again significantly higher for current violent offenders than those on sentence for other types of offences. Lastly, the CAVS was moderately predictive of estimated risk of reconviction and re‐imprisonment. Overall these results suggest that this scale measures the construct of attitudes to criminal violence, which partially overlaps two other constructs: attitudes to aggression and attitudes to crime. Aggr. Behav. 30:484–503, 2004. © 2004 Wiley‐Liss, Inc.
A new adaptive algorithm for reducing non‐linear effects from saturation in active noise control systems
Authors: Costa Márcio H. , Bermudez José Carlos M.
Published: November 2004

Adaptive algorithms applied to active noise and vibration control are frequently designed for maximum performance in linear environments. In many cases, non‐linear effects can severely impair the adaptive algorithm performance. One of the most common non‐linear effects is saturation, which can occur at the electronic circuits that drive the acoustic or mechanical transducers. An effective solution to mitigate such non‐linear distortions is to embed an automatic control of the non‐linear effects within the adaptive algorithm. Algorithms that use this approach are called minimum effort adaptive filters. This work presents a new minimum effort algorithm (MOV‐FXLMS), based on the minimum output variance least mean square estimator, for situations in which the influence of the secondary path cannot be neglected and its output is constrained by a saturation non‐linearity. Analytical expressions are obtained for the behaviour of the mean weight vector and for the mean square error for Gaussian inputs and slow learning. Monte Carlo simulations show excellent agreement with the predictions of the theoretical model. The optimum penalty factor (a design parameter of the MOV‐FXLMS algorithm) is determined as a function of the system's degree of non‐linearity. The new algorithm provides an unbiased solution to the associated non‐linear mean square estimation problem for small estimation errors of the secondary path and degree of non‐linearity. Robustness of the algorithm's performance to such errors is addressed. The new algorithm is compared with the conventional FXLMS algorithm for performance. Copyright © 2004 John Wiley & Sons, Ltd.
A fast‐array Kalman filter solution to active noise control
Authors: Fraanje Rufus , Sayed Ali H. , Verhaegen Michel , Doelman Niek J.
Published: November 2004

A Kalman filter solution to active control and its fast‐array implementation are provided. The adaptive control problem is formulated as a state‐estimation problem and no interchanging of the adaptive filter and the secondary‐path is imposed. Moreover, no estimate of the disturbance signal is needed, and we exploit the structure in the state–space matrices to derive a fast‐array implementation. A minimum variance estimate of the controller coefficients and the secondary path state is obtained. When there is no uncertainty in the secondary path, state equivalence with the modified filtered‐RLS algorithm is proven. Using exponential forgetting, the analysis shows that in the generation of the filtered reference signal in the modified filtered‐RLS, exponential forgetting should be incorporated too. Simulations show the superiority in convergence of the fast‐array Kalman algorithm over the fast‐array modified filtered‐RLS algorithm. Copyright © 2004 John Wiley & Sons, Ltd.
Characterization of Nanocarbons Produced by CVD of Ethylene in Alumina or Alumino‐Silicate Matrices
Authors: Ciambelli P. , Sannino D. , Sarno M. , Nagy J.B.
Published: November 2004

Alumina and alumino‐silicate matrices have been used to produce nanocarbons by ethylene CVD. Bundles of aligned, opened multi wall carbon nanotubes were obtained with alumina membrane (see Figure), while with beta zeolite ultra high porosity carbon (BET surface area >2000 m2/g) was formed.
Heterogeneous basis of the type VIB form of Ehlers–Danlos syndrome (EDS VIB) that is unrelated to decreased collagen lysyl hydroxylation
Authors: Walker L.C. , Overstreet M.A. , Willing M.C. , Marini J.C. , Cabral W.A. , Pals G. , Bristow J. , Atsawasuwan P. , Yamauchi M. , Yeowell Heather N.
Published: November 2004

Skin fibroblasts from the majority of patients with the clinical diagnosis of Ehlers–Danlos syndrome type VI (EDS VI; kyphoscoliosis type), have significantly decreased lysyl hydroxylase (LH) activity due to mutations in the LH1 gene (classified as EDS VIA: OMIM no. 225400). A rare condition exists in which patients are clinically similar but have normal levels of LH activity (designated EDS VIB: OMIM no. 229200). To define the biochemical defect, we have examined cultured fibroblasts from four EDS VIB patients for changes in the levels of the mRNAs for LH1, LH2, and LH3, collagen cross‐linking patterns, and the extent of lysine hydroxylation of type I collagen α chains. Although normal levels of LH1 mRNA were observed in all four patients, in two patients the levels of LH2 mRNA were decreased by >50%, and a similar decrease was observed in LH3 mRNA in the other two patients. A distinct pattern of collagen cross‐links, indicative of decreased lysyl hydroxylation, could be identified in EDS VIA patients, but there was no clear correlation between collagen cross‐link pattern and changes in the individual LH mRNAs in EDS VIB patients. Linkage to tenascin‐X was excluded in these patients. This study suggests that the basis for this form of EDS VI is genetically heterogeneous, and that alternative pathways in addition to lysine hydroxylation of collagen may be affected. © 2004 Wiley‐Liss, Inc.
Postnatal maturation of human GABAA receptors measured with positron emission tomography
Authors: Chugani Diane C. , Muzik Otto , Juhász Csaba , Janisse James J. , Ager Joel , Chugani Harry T.
Published: November 2004

During brain development in nonhuman primates, there are large changes in GABAA receptor binding and subunit expression. An understanding of human GABAA receptor ontogeny is highly relevant in elucidating the pathophysiology of neurodevelopmental disorders in which GABAergic mechanisms play a role as well as in understanding differences that occur during development in the pharmacology of drugs acting on this system. We have measured age‐related changes in the brain distribution of the GABAA receptor complex in vivo using positron emission tomography (PET) in epileptic children under evaluation for surgical treatment. PET imaging was performed using the tracer [11C]flumazenil (FMZ), a ligand that binds to α subunits of the GABAA receptor. FMZ binding was quantified using a two‐compartment model yielding values for the volume of distribution (VD) of the tracer in tissue. All brain regions studied showed the highest value for FMZ VD at the youngest age measured (2 years), and the values then decreased exponentially with age. Medial temporal lobe structures, primary visual cortex, and thalamus showed larger differences between values for age 2 years and adults (approximately 50% decrease) than did basal ganglia, cerebellum, and other cortical regions (25–40% decreases). Furthermore, subcortical regions reached adult values earlier (14–17.5 years) than did cortical regions (18–22 years). The ontogeny data of FMZ VD from children may contribute to understanding regional differences in synaptic plasticity as well as improve rational therapeutic use of drugs acting at the GABAA receptor in the pediatric population.
Hemispheric influence on autonomic modulation and baroreflex sensitivity
Authors: Hilz Max J. , Dütsch Matthias , Perrine Ken , Nelson Peter K. , Rauhut Ute , Devinsky Orrin
Published: November 2004

Several studies suggest hemispheric lateralization of autonomic cardiovascular control. There is controversy regarding which hemisphere dominates sympathetic or parasympathetic activity. Hemispheric influences on baroreflex sensitivity (BRS) have not yet been evaluated. To determine hemispheric autonomic control in epilepsy patients, we assessed cardiovascular and baroreflex modulation before and during hemispheric inactivation. For 15 patients with drug‐refractory epilepsy, we analyzed autonomic heart rate (HR) and blood pressure (BP) modulation and BRS before and during left and right intracarotid amobarbital procedure (IAP). After Blackman‐Tukey spectral analysis, we calculated the low‐frequency (LF: 0.04–0.15 Hz) and high‐frequency (HF: 0.15–0.5 Hz) power of HR and BP as well as BRS as the LF transfer function gain between BP and HR. Right hemispheric inactivation induced a significant decrease of BP and an increase of HF power of HR and BP (p< 0.05). Left inactivation increased HR, BP, and LF power of both signals and decreased BRS by nearly 30% (p< 0.05). The results confirm previous IAP studies showing sympathetic lateralization in the right hemisphere and, moreover, demonstrate parasympathetic predominance and up‐regulation of BRS in the left hemisphere. In epilepsy patients, unilateral electrical activity might derange autonomic balance between both hemispheres and contribute to cardiovascular dysregulation and sudden fatalities.
Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis
Authors: Johnston James B. , Silva Claudia , Gonzalez Guido , Holden Janet , Warren Kennith G. , Metz Luanne M. , Power Christopher
Published: November 2004

The nucleoside adenosine has been shown to control the production of proinflammatory molecules through its actions on cell surface purine receptors. Previously, we have reported that the adenosine A1 receptor (A1AR) regulates tumor necrosis factor‐α (TNF‐α) and interleukin‐6 (IL‐6) expression and exhibits diminished function in patients with multiple sclerosis (MS; Mayne et al., Ann Neurol 1999;45:633–639). In the present study, A1AR expression in both brain and peripheral blood mononuclear cells (PBMC) from MS and control groups was characterized by fluorescence‐activated cell sorting (FACS), reverse transcriptase‐polymerase chain reaction (RT‐PCR), and immunohistochemical analyses. FACS analyses of PBMC revealed that A1AR expression was chiefly detectable on CD14‐positive cells and was reduced by 53.1% (p < 0.01) in MS patients compared to controls. A1AR mRNA levels were reduced by 43.1% (p < 0.001) in the brains of MS patients compared to patients with other neurological diseases and controls. A1AR protein expression in brain was detected primarily in CD45‐positive glial cells and was markedly diminished in MS patients. The analysis of A1AR transcripts in the brain revealed that the A1AR‐β transcript was diminished (49.2%) in MS patients compared to controls (p < 0.002). These results indicate that the A1AR, expressed principally on cells of monocyte/macrophage lineage in both brain and blood, is selectively diminished in MS patients. Reduction of the A1AR‐β transcript in MS patients suggests that dysregulated splicing may influence A1AR protein levels, potentially leading to increased macrophage activation and central nervous system inflammation.
Subclinical cerebellar impairment in the common types of migraine: A three‐dimensional analysis of reaching movements
Authors: Sándor Peter S. , Mascia Addolorata , Seidel Laurence , De Pasqua Victor , Schoenen Jean
Published: November 2004

Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or cerebellar ataxia. CACNA1A codes for the α1 subunit of P/Q‐Ca2+ channels and is highly expressed in the cerebellum. Using a pointing paradigm and infrared optoelectronic tracking system, we found subclinical hypermetria and other subtle cerebellar signs in the common forms of migraine. These were more pronounced in migraine with than without aura. Whether this reflects involvement of Ca2+ channel genes in the common types of migraine needs to be investigated by genetic analyses.
Parkinson's disease is not associated with the combined α‐synuclein/apolipoprotein E susceptibility genotype
Authors: Khan Naheed , Graham Elizabeth , Dixon Peter , Morris Christopher , Mander Adrian , Clayton David , Vaughan J. , Quinn Niall , Lees Andrew , Daniel Susan , Wood Nicholas , De Silva Rohan
Published: November 2004

A recent study showed significant association of sporadic Parkinson's disease with a polymorphism within the α‐synuclein gene and closely linked DNA markers on chromosome 4q and the APOE ε4 allele. A combined α‐synuclein/APOE‐ε4 genotype increased the relative risk of developing Parkinson's disease 12‐fold. We failed to confirm this association in a much larger sample of histopathologically proven cases of Parkinson's disease and controls.
Potential for creatine and other therapies targeting cellular energy dysfunction in neurological disorders
Authors: Tarnopolsky Mark A. , Beal M. Flint
Published: November 2004

Substantial evidence indicates that bioenergetic dysfunction plays either a primary or secondary role in the pathophysiology of cell death in neurodegenerative and neuromuscular disorders, and even in normal aging. Agents that ameliorate bioenergetic defects may therefore be useful in therapy. Creatine, which increases muscle and brain phosphocreatine concentrations, and may inhibit the activation of the mitochondrial permeability transition, protects against neuronal degeneration in transgenic murine models of amyotrophic lateral sclerosis and Huntington's disease and in chemically mediated neurotoxicity. Initial studies of creatine use in humans appear promising; however, further long‐term, well‐designed trials are needed. Coenzyme Q10, Gingko biloba, nicotinamide, riboflavin, carnitine, lipoic acid, and dichloroacetate are other agents which may have beneficial effects on energy metabolism, but the preclinical and clinical evidence for efficacy in neurological diseases remains limited. These compounds are widely used as dietary supplements; however, they must be subjected to rigorous evaluation through randomized, double‐blinded trials to establish efficacy, cost‐effectiveness and safety in neurological disorders.
The resistance to ischemia of white and gray matter after stroke
Authors: Falcao Antonio L. E. , Reutens David C. , Markus Romesh , Koga Masatoshi , Read Stephen J. , Tochon‐Danguy Henri , Sachinidis John , Howells David W. , Donnan Geoffrey A.
Published: November 2004

A contributing factor to the failure of trials of neuroprotectants in acute ischemic stroke may be the differing vulnerability to ischemia of white compared with gray matter. To address this issue, we determined to establish the existence of potentially viable tissue in white matter and its evolution to infarction or salvage in both gray and white matter compartments in patients with ischemic stroke. Twenty‐seven patients (mean age, 73.4 years) at a median of 16.5 hours after symptom onset were studied using the hypoxic marker 18F‐misonidazole with positron emission tomography (PET). Tissue was segmented using an magnetic resonance probabilistic map. Although there was a greater volume of initially “at‐risk tissue” in gray matter (58.3cm3, 29.9–93.0cm3) than white matter (42.0cm3, 15.8–74.0cm3; p < 0.001) at the time of PET imaging, a higher proportion of this was still potentially viable in white matter (41.4%, 4.6–74.5%) than in gray matter (23.6%, 3.2–61.1%; p < 0.05). However, a similar proportion in each compartment spontaneously survived. These data provide evidence for the existence of potentially salvageable tissue in human white matter and is consistent with it having a similar or even greater resistance to ischemia than gray matter. For the latter possibility, alternative therapeutic strategies may be required for its salvage. Ann Neurol 2004;56:695–701
Vertical conjugate eye deviation in postresuscitation coma
Authors: Johkura Ken , Komiyama Atsushi , Kuroiwa Yoshiyuki
Published: November 2004

Vertical eye deviation in hypoxic coma is considered to be rare. In contrast, we found that in a consecutive series of 50 postresuscitation comatose patients, 28 (56.0%) developed tonic upward or downward eye deviation. We suggest that both the upward and the downward deviations resulted from diffuse cerebrocerebellar damage sparing the brainstem. Upward deviation is an early sign, whereas downward deviation appears later and generally implies a transition to the vegetative state. Ann Neurol 2004
Surface chemistry and mechanical property changes of wood‐flour/high‐density‐polyethylene composites after accelerated weathering
Authors: Stark Nicole M. , Matuana Laurent M.
Published: November 2004

Although wood–plastic composites have become more accepted and used in recent years and are promoted as low‐maintenance, high‐durability building products, they do experience a color change and a loss in mechanical properties with accelerated weathering. In this study, we attempted to characterize the modulus‐of‐elasticity (MOE) loss of photostabilized high‐density polyethylene (HDPE) and composites of wood flour and high‐density polyethylene (WF/HDPE) with accelerated weathering. We then examined how weathering changed the surface chemistry of the composites and looked at whether or not the surface changes were related to the MOE loss. By examining surface chemistry changes, we hoped to begin to understand what caused the weathering changes. The materials were left unstabilized or were stabilized with either an ultraviolet absorber or pigment. After 1000 and 2000 h of accelerated weathering, the samples were tested for MOE loss. Fourier transform infrared (FTIR) spectroscopy was employed to monitor carbonyl and vinyl group formation at the surface. Changes in the HDPE crystallinity were also determined with FTIR techniques. It was determined that structural changes in the samples (carbonyl group formation, terminal vinyl group formation, and crystallinity changes) could not be reliably used to predict changes in MOE with a simple linear relationship. This indicated that the effects of crosslinking, chain scission, and crystallinity changes due to ultraviolet exposure and interfacial degradation due to moisture exposure were interrelated factors for the weathering of HDPE and WF/HDPE composites. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2263–2273, 2004
Studies on the blends of polycarbonate and highly branched polystyrene
Authors: Qiang Ren , Aiying Li , Bibiao Jiang , Dongliang Zhang , Jianhai Chen
Published: November 2004

A highly branched polystyrene (HBPS) was synthesized via the copolymerization of 4‐(chloromethyl) styrene with styrene using the self‐condensing atom transfer radical polymerization method. The addition of this highly branched polystyrene as a melt modifier for polycarbonate (PC) was attempted. Indeed, the results show that the addition of highly branched polystyrene can decrease the melt viscosity of PC with little change in mechanical properties, although the blends do exhibit lower thermal stability compared with pure PC. Extrapolation shows that all of the blends have an initial weight loss temperature above 450°C with a statistic heat‐resistant index Ts above 225°C. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2425–2430, 2004
Effect of lignin particles as a nucleating agent on crystallization of poly(3‐hydroxybutyrate)
Authors: Weihua Kai , He Yong , Asakawa Naoki , Inoue Yoshio
Published: November 2004

The effect of lignin fine powder, as a new kind of nucleating agent, on the crystallization process of poly(3‐hydroxybutyrate) (PHB) was studied. The kinetics of both isothermal and nonisothermal crystallization processes from the melt for both pure PHB and PHB/lignin blend was studied by means of differential scanning calorimetry. Lignin shortened the crystallization half‐time t1/2 for isothermal crystallization. The activation energy ΔE for PHB/lignin and pure PHB in the isothermal crystallization process was −237.40 and −131.22 kJ/mol, respectively, clearly indicating that the crystallization of the PHB/lignin blend was more favorable than that of pure PHB from a thermodynamic perspective. At the same time, according to polarized optical microscopy, the rate of spherulitic growth from the melt increased with the addition of lignin, which is ascribed to the reduction of surface fold energy σe, that is, σe is 59.2 × 10−3 and 41.6 × 10−3 J m−2 for pure PHB and PHB/lignin, respectively. Polarized optical microscopy also showed that the spherulites found in PHB with lignin were smaller in size and greater in number than those found in pure PHB. The wide‐angle X‐ray diffraction indicated that an addition of lignin caused no change in the crystal structure and degree of crystallinity. These results indicated that lignin is a good nucleating agent for the crystallization of PHB. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2466–2474, 2004
Synthesis and characterization of copolymers of bromoacrylated methyl oleate
Authors: Eren Tarik , Küsefoğlu Selim H.
Published: November 2004

In this study, methyl oleate was bromoacrylated in the presence of N‐bromosuccinimide and acrylic acid in one step. Homopolymers and copolymers of bromoacrylated methyl oleate (BAMO) were synthesized by free radical bulk polymerization and photopolymerization techniques. Azobisisobutyronitrile (AIBN) and 2,2‐dimethoxy‐2‐phenyl‐acetophenone were used as initiators. The new monomer BAMO was characterized by FTIR, GC‐MS, 1H, and 13C‐NMR spectroscopy. Styrene (STY), methylmethacrylate (MMA), and vinyl acetate (VA) were used for copolymerization. The polymers synthesized were characterized by FTIR, 1H‐NMR, 13C‐NMR, and differential scanning calorimetry (DSC). Molecular weight and polydispersities of the copolymers were determined by GPC analysis. Ten different feed ratios of the monomers STY and BAMO were used for the calculation of reactivity ratios. The reactivity ratios were determined by the Fineman–Ross and Kelen–Tudos methods using 1H‐NMR spectroscopic data. The reactivity ratios were found to be rsty = 0.891 (Fineman–Ross method), 0.859 (Kelen–Tudos method); rbamo = 0.671 (Fineman–Ross method), 0.524 (Kelen–Tudos method). © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 94: 2475–2488, 2004
A Novel Dipeptide‐based HIV Protease Inhibitor Containing Allophenylnorstatine
Authors: Abdel‐Rahman Hamdy M. , El‐Koussi Nawal A. , Alkaramany Gamal S. , Youssef Adel F. , Kiso Yoshiaki
Published: November 2004

Dipeptide analogues incorporating allophenylnorstatine [Apns; (2S, 3S)‐3amino‐2‐hydroxy‐4‐phenylbutyric acid] as a transition state mimic at the scissile bond were designed and synthesized in the hope of obtaining a novel KNI series of HIV protease inhibitors. The precursors, N‐P2′‐3‐(2S, 3S)‐3‐(tert‐butyloxy‐carbonyl)amino‐2‐hydroxy‐4‐phenylbutanoyl)‐5, 5‐dimethylthiazolidine‐4‐carboxamide (N‐Boc‐Apns‐Dmt‐P2′) 4a–p were prepared by deprotection of the synthones N‐P2′‐(tert‐butyloxycarbonyl)‐5, 5‐dimethylthiazolidine‐4‐carboxamide (Boc‐Dmt‐P2′) 2a–p, then coupling with (2S, 3S)3‐(tert‐butyloxycarbonyl)amino‐2‐hydroxy‐4‐phenylbutanoic acid (N‐Boc‐Apns‐OH) 3. The deprotected intermediates 4 were coupled with the activated carboxyl groups of the P2 ligands to afford the target dipeptides. In this work, we fixed at the P2 site either a 2, 6‐dimethylphenoxyacetyl or a 3‐hydroxy‐2‐methylbenzoyl group. Substitutes at the P2′ site were varied to afford the members of the series 7 and 8. Improved activity of most of the members of series 8 relative to their analogues of series 7 can be partially attributed to the differences in the structures of the P2 moieties. Positional isomerism in the P2′ moieties significantly affected the activity and polarity of the target.
From hypocaust to hyperbola: ground‐penetrating radar surveys over mainly Roman remains in the UK
Authors: Linford Neil
Published: November 2004

Ground‐penetrating radar (GPR) survey can provide a wealth of information when applied to the investigation of buried remains. The strength of the GPR technique lies both in its suitability to a wide range of site conditions and the complementary nature of the data in comparison with other geophysical techniques. However, GPR is not infallible, relying on the careful selection of suitable sites and the application of appropriate data processing and visualization routines to maximize the potential of the acquired data. This paper demonstrates the use of GPR over a variety of mainly Roman remains surveyed recently by English Heritage, within the UK, ranging in scale from an in situ mosaic pavement threatened by water damage at Bignor Roman villa, West Sussex to an entire, suspected amphitheatre at Richborough Castle, Kent. The influence of site conditions, such as soil conductivity and topography, is also considered and a novel application of principal components analysis is presented to enhance the identification of significant anomalies from data where rapid signal attenuation has occurred. This latter technique considers the correlation of GPR response between adjacent amplitude time‐slices in an attempt to isolate the response due to significant buried wall footings from the more cluttered signal of the surrounding clay‐rich soil. Where appropriate, URL links are provided to computer animations of the GPR data that may often serve to accentuate subtle variations through the stratigraphy of the site. Copyright © 2004 John Wiley & Sons, Ltd.