bluuebunny/crossref_metadata_2025 huggingface dataset:
Acrylonitrile–butadiene–styrene toughened nylon 6: The influences of compatibilizer on morphology and impact properties
Authors: Araújo E. M. , Hage E. , Carvalho A. J. F.
Published: December 2002

Polymer alloys have been used as an alternative to obtain polymeric materials with unique physical properties. Generally, the polymer mixture is incompatible, which makes it necessary to use a compatibilizer to improve the interfacial adhesion. Nylon 6 (PA6) is an attractive polymer to use in engineering applications, but it has processing instability and relatively low notched impact strength. In this study, the acrylonitrile–butadiene–styrene (ABS) triblock copolymer was used as an impact modifier for PA6. Poly(methyl methacrylate‐co‐maleic anyhydride) (MMA‐MA) and poly(methyl methacrylate‐co‐glycidyl methacrylate) (MMA‐GMA) were used as compatibilizers for this blend. The morphology and impact strength of the blends were evaluated as a function of blend composition and the presence of compatibilizers. The blends compatibilized with maleated copolymer exhibited an impact strength up to 800 J/m and a morphology with ABS domains more efi8ciently dispersed. Moderate amounts of MA functionality in the compatibilizer (∼5%) and small amounts of compatibilizer in the blend (∼5%) appear sufficient to improve the impact properties and ABS dispersion. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 842–847, 2003
Failure analysis of rubber toughened epoxy resin
Authors: Nigam Vineeta , Setua D. K. , Mathur G. N.
Published: December 2002

Failure of the blends of epoxy cresol novolac resin (ECN) with varied proportions of carboxy terminated polybutadiene (CTPB) liquid functional rubber was studied. Addition of CTPB improves toughness as reflected in the improvement of tensile, flexural, and impact properties. However, 10 wt % of CTPB was the optimum concentration beyond which a rapid fall of properties, in all cases, was observed. Surface topography of the fractured surfaces, studied by scanning electron microscopy and atomic force microscopy, revealed marked changes in the phase morphology due to addition of rubber and also accounted for the variation of the strength properties. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 87: 861–868, 2003
Mitochondrial localization of glucocortocoid receptor in glial (Müller) cells in the salamander retina
Authors: Psarra Anna‐Maria G. , Bochaton‐Piallat Marie‐Luce , Gabbiani Giulio , Sekeris Constantine E. , Tsacopoulos Marcos
Published: December 2002

Glucocorticoid hormones regulate the transcription of nuclear genes by way of their receptors. In addition, these hormones modulate mitochondrial gene transcription by mechanisms that remain poorly understood. Using immunofluorescence labeling in isolated Müller and photoreceptor cells and in intact salamander retina, we found that the glucocorticoid receptor (GR) is localized in both cell types. Confocal laser scanning microscopy and double staining with cytochrome oxidase (COX) showed that GR is localized in the mitochondria of Müller cells, but not in the mitochondria of photoreceptors. GR also colocalizes with glutamine synthetase (GS) in the cytoplasm of Müller cells. GR is also localized in the microvilli of the distal process of Müller cells and in the synaptic terminal of photoreceptors. Pre‐incubation of Müller cells with 1 μM dexamethasone (DEX) for 7 h led to greater than 50% inhibition of the glutamate‐induced increase in mitochondrial NADH. This late effect of glucocorticoids on glutamate metabolism could be ascribed, in part, to a direct action of steroid hormones on mitochondrial metabolism. GLIA 41:38–49, 2003. © 2003 Wiley‐Liss, Inc.
Induction of matrix metalloproteinase‐9 (MMP‐9) in lipopolysaccharide‐stimulated primary astrocytes is mediated by extracellular signal‐regulated protein kinase 1/2 (Erk1/2)
Authors: Lee Woo Jong , Shin Chan Young , Yoo Byoung Kwon , Ryu Jae Ryun , Choi Eui Yul , Cheong Jae Hoon , Ryu Jong Hoon , Ko Kwang Ho
Published: December 2002

In the present study, we investigated whether the activation of protein kinase C (PKC) and extracellular signal‐regulated kinase 1/2 (Erk1/2) are involved in the induction of MMP‐9 in lipopolysaccharide (LPS)–stimulated primary astrocytes. The expression of MMP‐9 but not MMP‐2 was increased by LPS. LPS treatment induced activation of Erk1/2 within 30 min, which was dose‐dependently inhibited by PD98059, a specific inhibitor of the Erk kinase (MEK). In this condition, PD98059 blocked the increase in MMP‐9 protein and mRNA level as well as gelatin‐digesting activity. Inhibition of PKC activity blocked the LPS‐induced activation of Erk1/2 as well as MMP‐9 expression. In addition, activation of PKC by phorbol myristoyl acetate (PMA) activated Erk1/2 with concomitant increase in MMP‐9 production. Moreover, treatment of PD98059 dose‐dependently decreased the PMA‐induced MMP‐9 expression. The results from the present study suggest that induction of MMP‐9 by LPS in rat primary astrocytes is mediated, at least in part, by the sequential activation of PKC and Erk1/2. The Erk1/2‐mediated MMP‐9 induction may provide insights into the regulation of MMP‐9 production in CNS, which may occur in vivo in pathological situations such as CNS inflammation. GLIA 41:15–24, 2003. © 2003 Wiley‐Liss, Inc.
Loss of microglial ramification in microglia‐astrocyte cocultures: Involvement of adenylate cyclase, calcium, phosphatase, and Gi‐protein systems
Authors: Kalla Roger , Bohatschek Marion , Kloss Christian U.A. , Krol Janna , Von Maltzan Xenia , Raivich Gennadij
Published: December 2002

Reduction in microglial branching is a common feature in brain pathology and culminates in the transformation into small, rounded, microglia‐derived phagocytes in the presence of neural debris. The molecular factors responsible for this transformation are unknown. Here we explored the effect of different classes of intra‐ and extracellular stimuli in vitro on the morphology of ramified microglia cultured on a confluent astrocyte substrate. These studies showed a strong dose‐dependent effect for the Ca2+ ionophore calcimycine/A21837 (50 μM) and for dibutyryl‐cAMP (1 mM), with a loss of microglial ramification. Direct activation of the adenylate cyclase with forskolin (0.1 mM) also led to the disappearance of microglial branching. Okadaic acid (70 nM), the inhibitor of protein phosphatases 1 and 2A (PP1/PP2A), and pertussis toxin (12.5 μg/ml), a Gi‐protein inhibitor, also showed similar effects. No effect was observed for dibutyryl‐cGMP or for UTP; addition of ATP had a moderate effect, but only at very high, probably nonphysiological concentrations (100 mM). Extracellular matrix components such as keratatan‐sulfate, integrin receptor blockers, the disintegrins kistrin, echistatin, and flavoridin, or the serine protease thrombin all had no effect. Addition of prostaglandin D2 (PGD2), a molecule produced by activated microglial cells, had a transforming effect, but at concentrations two orders of magnitude higher than that of established PGD2 receptors. In summary, addition of agents causing intracellular elevation of Ca2+ and cAMP or inhibition of Gi‐proteins and phosphatases to ramified microglia cultured on top of confluent astrocytes leads to a rapid loss of microglial branching. Signaling cascades controlled by these molecules may play an important role in the regulation of this common physiological process in the injured brain. GLIA 41:50–63, 2003. © 2003 Wiley‐Liss, Inc.
Single neuron burst firing in the human hippocampus during sleep
Authors: Staba Richard J. , Wilson Charles L. , Fried Itzhak , Engel Jerome
Published: December 2002

Although there are numerous non‐primate studies of the single neuron correlates of sleep‐related hippocampal EEG patterns, very limited hippocampal neuronal data are available for correlation with human sleep. We recorded human hippocampal single neuron activity in subjects implanted with depth electrodes required for medical diagnosis and quantitatively evaluated discharge activity from each neuron during episodes of wakefulness (Aw), combined stage 3 and 4 slow‐wave sleep (SWS), and rapid eye movement (REM) sleep. The mean firing rate of the population of single neurons was significantly higher during SWS and Aw compared with REM sleep (p = 0.002; p < 0.0001). In addition, burst firing was significantly greater during SWS compared with Aw (p = 0.001) and REM sleep (p < 0.0001). The synchronized state of SWS and associated high‐frequency burst discharge found in human hippocampus may subserve functions similar to those reported in non‐primate hippocampus that require burst firing to induce synaptic modifications in hippocampal circuitry and in hippocampal projections to neocortical targets that participate in memory consolidation. Hippocampus 2002;12:724–734. © 2002 Wiley‐Liss, Inc.
Transcriptional profiling reveals regulated genes in the hippocampus during memory formation
Authors: Donahue Christine P. , Jensen Roderick V. , Ochiishi Tomoyo , Eisenstein Ingrid , Zhao Mingrui , Shors Tracey , Kosik Kenneth S.
Published: December 2002

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real‐time polymerase chain reaction. These genes were growth hormone (GH), c‐kit receptor tyrosine kinase (c‐kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor‐β (NGF‐β), Jun oncogene (c‐Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal‐dependent associative memories. Hippocampus 2002;12:821–833. © 2002 Wiley‐Liss, Inc.
Human hippocampus and viewpoint dependence in spatial memory
Authors: King John A. , Burgess Neil , Hartley Tom , Vargha‐Khadem Faraneh , O'Keefe John
Published: December 2002

Virtual reality was used to sequentially present objects within a town square and to test recognition of object locations from the same viewpoint as presentation, or from a shifted viewpoint. A developmental amnesic case with focal bilateral hippocampal pathology showed a massive additional impairment when tested from the shifted viewpoint compared with a mild, list length‐dependent, impairment when tested from the same viewpoint. While the same‐view condition could be solved by visual pattern matching, the shifted‐view condition requires a viewpoint independent representation or an equivalent mechanism for translating or rotating viewpoints in memory. The latter mechanism was indicated by control subjects' response latencies in the shifted‐view condition, although the amnesic case is not impaired in tests of mental rotation of single objects. These results show that the human hippocampus supports viewpoint independence in spatial memory, and suggest that it does so by providing a mechanism for viewpoint manipulation in memory. In addition, they suggest an extremely sensitive test for human hippocampal damage, and hint at the nature of the hipppocampal role in episodic recollection. Hippocampus 2002;12:811–820. © 2002 Wiley‐Liss, Inc.
Motor response to levodopa and the evolution of motor fluctuations in the first decade of treatment of Parkinson's disease
Authors: McColl Craig D. , Reardon Katrina A. , Shiff Mark , Kempster Peter A.
Published: December 2002

Thirty‐four patients with Parkinson's disease were followed for a mean period of 8 years from the time of initiation of levodopa medication. Levodopa response was charted from the starting point of pharmacological treatment to give a longitudinal point of view of the changes that evolve as the disease progresses. Objective measurements of the motor response to levodopa test‐doses were made at approximately three yearly intervals. Motor fluctuations developed in 58% of the patient group after a mean treatment period of 35 months. Dyskinesia developed in parallel with fluctuations but appeared on average 7 months before symptomatic wearing‐off effects of levodopa doses. The patients with motor fluctuations had significantly better responses to levodopa. By contrast, nonfluctuators were more prone to develop increasing midline motor disability affecting speech, gait and balance. Comparison of test‐dose and pretreatment scores suggested that a substantial long‐duration response to levodopa remains after many years of treatment, and that lateralized motor deficits show a stronger long duration response than midline ones. Motor fluctuations are a consequence of disease progression but their early development is, on balance, associated with better long‐term functional ability because these patients have the greater capacity to respond to pharmacological treatment. © 2002 Movement Disorder Society
Switching of movement direction is central to parkinsonian bradykinesia in sit‐to‐stand
Authors: Mak Margaret K.Y. , Hui‐Chan Christina W.Y.
Published: December 2002

Patients with Parkinson's disease (PD) are known to manifest slowness in movements. We sought to identify the particular kinematic and kinetic disorders that contribute to the slowness in performing sit‐to‐stand in these patients. Two inter‐related studies were carried out. In the first study, 20 patients with PD and 20 control subjects were instructed to perform sit‐to‐stand at a natural speed. In the second study, 15 control subjects were instructed to simulate the slower speed of sit‐to‐stand of the patients identified in the first study. Kinematic and kinetic data were recorded by a PEAK motion analysis system and two force platforms. The results showed that patients with PD generated smaller peak horizontal and vertical velocities during the task. They took a longer time to complete each individual phase as well as the whole movement of sit‐to‐stand. Patients also produced smaller peak hip flexion and ankle dorsiflexion joint torques and had prolonged time‐to‐peak torques from sit‐to‐stand onset. When control subjects simulated the patients' speed of sit‐to‐stand, there was no difference in all the kinematic and kinetic data between groups. The only exception was that they exhibited a shorter transition time between peak horizontal velocity (flexion phase) and seat‐off (extension phase) than the patients. This study demonstrated that the slowness of PD patients during sit‐to‐stand at a natural speed could be attributed to inadequate peak hip flexion and ankle dorsiflexion torques, a prolonged torque production, as well as a difficulty in switching from the flexion to extension direction during sit‐to‐stand. As the latter difficulty persisted when the control subjects performed the task at a speed similar to that of the patients, our findings suggest that a fundamental problem of patients with Parkinson's disease could be a switch between movement directions. © 2002 Movement Disorder Society
Selective loss of pyramidal neurons in the pre‐supplementary motor cortex in Parkinson's disease
Authors: MacDonald Virginia , Halliday Glenda M.
Published: December 2002

The nonprimary motor cortices have not previously been studied in Parkinson's disease, despite the selective pattern of dysfunction observed in these regions. In particular, the pre‐supplementary motor region is consistently underactive, with successful treatments correlating with increased excitatory drive to nonprimary motor regions. This finding could suggest a primary cortical abnormality in the pre‐supplementary motor area (pre‐SMA) in Parkinson's disease. We analysed and compared neuronal number in the pre‐SMA and dorsolateral premotor cortical regions in 5 cases of Parkinson's disease and 5 controls. For each cortical region, the total neuronal number as well as the estimated numbers of subpopulations of interneurons and pyramidal neurons was quantified using previously published unbiased techniques. The results showed a significant loss of cortico–cortical projecting pyramidal neurons in the pre‐SMA with no loss of other pyramidal neurons or interneurons either in this region or in the dorsolateral premotor region. These findings indicate a highly selective loss of pyramidal cells in the pre‐SMA in Parkinson's disease, consistent with previous imaging findings in this disease. Our results implicate the degeneration of the premotor projection from the pre‐SMA, along with dopaminergic basal ganglia dysfunction, in the pathogenesis of Parkinson's disease. © 2002 Movement Disorder Society
Progressive delayed‐onset dystonia after cerebral anoxic insult in adults
Authors: Kuoppamäki Mikko , Bhatia Kailash P. , Quinn Niall
Published: December 2002

The basal ganglia, especially the globi pallidi (GP), are highly vulnerable to generalized cerebral anoxia/hypoxia. We report on 2 new cases with delayed‐onset generalized dystonia due to cerebral anoxia. The onset of dystonia in both of our patients was delayed by about 2 months. In both cases, the unusual feature was the progressive worsening and the spread of dystonia over many years after delayed onset. Dystonia progressed for 16 years in Case 1 and for 4 years in Case 2. Furthermore, initial magnetic resonance imaging (MRI) scan of Case 1 showed mild changes of the internal capsule sparing the basal ganglia. Years later, in line with clinical progression, the follow‐up MRI scan showed isolated bilateral lesions involving the entire GP. MRI scans in Case 2 showed bilateral lesions of caudate and lentiform nuclei. There may be several mechanisms underlying delayed and progressive symptoms after time‐limited brain anoxia. We hypothesize that anoxia‐induced excitotoxicity resulting in mitochondrial dysfunction and subsequent apoptosis may explain, at least partly, the delayed‐onset and progressive extrapyramidal syndromes seen in these patients. © 2002 Movement Disorder Society
An imaging study of parkinsonism among African‐Caribbean and Indian London communities
Authors: Hu Michele T.M. , Chaudhuri K. Ray , Jarosz Jozef , Yaguez Lidia , Brooks David J.
Published: December 2002

We previously reported on 131 parkinsonian patients of African‐Caribbean and Indian origin attending movement disorders clinics in six London Hospitals, of whom approximately 20% manifested atypical parkinsonism with a late‐onset, akinetic‐rigid predominant syndrome, postural instability and minimal resting tremor refractory to levodopa therapy and dopamine agonists (see Hu et al., Neurology 2000;54[Suppl.3]: A188 and Hu et al., Mov Disord 2000;15[Suppl.3]:S212). To better elucidate the phenotype of these atypical patients 18FDG/18F‐dopa positron emission tomography (PET) were performed in a subgroup to look for cortical and striatal metabolic changes suggestive of multiple system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), or dementia with Lewy bodies. Magnetic resonance imaging (MRI) rating of cerebral vascular lesion load, putaminal atrophy, and neuropsychological testing were also performed. Discriminant function analysis of 18F‐dopa/18FDG striatal metabolism in 43 patients failed to separate atypical ethnic minority from typical Caucasian Parkinson's disease (PD) patients. Additionally, atypical Indian and African‐Caribbean patients did not show cortical reductions in glucose metabolism suggestive of PSP, CBD, or DLB. Cerebral vascular lesion load rated in these patients did not differ between atypical and typical PD groups, and none of the atypical patients had MRI changes suggestive of MSA or PSP. Our results suggest the atypical parkinsonian phenotype seen in African‐Caribbean and Indian patients represents a levodopa‐refractory form of PD separate from MSA or PSP in most patients. © 2002 Movement Disorder Society
Beginning‐of‐dose and rebound worsening in MPTP‐treated common marmosets treated with levodopa
Authors: Kuoppamäki Mikko , Al‐Barghouthy Ghassan , Jackson Michael , Smith Lance , Zeng Bai‐Yun , Quinn Niall , Jenner Peter
Published: December 2002

A wide range of motor fluctuations develop in Parkinson's disease (PD) patients after prolonged levodopa (L‐dopa) treatment, but few experimental models exist in which these can be investigated. We report on motor fluctuations occurring in MPTP‐treated common marmosets (Callithrix jacchus) treated repeatedly with L‐dopa. All animals showed an improvement in motor function in response to L‐dopa, and rapidly developed peak‐dose dyskinesia. During the period of L‐dopa action, brief periods of immobility were occasionally observed. After acute L‐dopa challenge, animals exhibited a worsening of motor function before improvement, and after the beneficial response to L‐dopa declined, motor performance showed rebound worsening to below‐baseline values. Before L‐dopa challenge and during wearing‐off and rebound worsening, leg dystonias were observed. Although these findings cannot necessarily be generalized to all MPTP‐treated nonhuman primates, they demonstrate that MPTP‐treated marmosets show a range of different motor fluctuations analogous to those seen in PD patients chronically treated with L‐dopa. Therefore, 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐treated primates can provide a model in which the pathophysiology of treatment complications can be investigated. © 2002 Movement Disorder Society
Steele‐Richardson‐Olszewski syndrome in a patient with a single C212Y mutation in the parkin protein
Authors: Morales Blas , Martínez Armando , Gonzalo Isabel , Vidal Lidice , Ros Raquel , Gomez‐Tortosa Estrella , Rabano Alberto , Ampuero Israel , Sánchez Marina , Hoenicka Janet , García de Yébenes Justo
Published: December 2002

Steele‐Richardson‐Olszewski syndrome (SROS) is a neurodegenerative disorder of unknown aetiology, most frequently sporadic. Familial cases of SROS have been described. An intronic polymorphism of the tau gene is associated with sporadic SROS and mutations of the tau gene are present in atypical cases of SROS. The role of tau has been excluded in other families with pathology proven SROS, suggesting that this syndrome may have multiple causes. An 82‐year‐old patient, father of 3 children with autosomal recessive juvenile parkinsonism due to combined heterozygous mutations of the parkin gene, developed clinical features of SROS 2 years before death. The diagnosis was confirmed by pathology. He carried the C212Y mutation of the parkin gene and was homozygous for the A0 polymorphism and for the H1 haplotype. The role of parkin in the processing of tau is discussed. © 2002 Movement Disorder Society
Phenomenology of “Lubag” or X‐linked dystonia–parkinsonism
Authors: Evidente Virgilio Gerald H. , Advincula Joel , Esteban Raymund , Pasco Paul , Alfon Jhoe Anthony , Natividad Filipinas F. , Cuanang Joven , Luis Amado San , Gwinn‐Hardy Katrina , Hardy John , Hernandez Dena , Singleton Andrew
Published: December 2002

X‐linked dystonia–parkinsonism (XDP), or Lubag syndrome, is known to cause progressive dystonia, with or without parkinsonism, among Filipino male adults with maternal roots from the Philippine island of Panay. We present cinematographic material of 11 cases of Lubag carrying the XDP haplotypes who manifest with a wide spectrum of movement disorders, including dystonia, tremor, parkinsonism, myoclonus, chorea, and myorhythmia. Because of overlapping features, Lubag patients are commonly misdiagnosed as idiopathic dystonia, essential tremor, Parkinson's disease, or Parkinson's‐plus syndromes. Thus, it is imperative to elicit an exhaustive family history in any Filipino male adult who presents with a movement disorder. © 2002 Movement Disorder Society
Clinical relevance of electrophysiological tests in the assessment of patients with Huntington's disease
Authors: Lefaucheur Jean‐Pascal , Bachoud‐Levi Anne‐Catherine , Bourdet Catherine , Grandmougin Thierry , Hantraye Philippe , Cesaro Pierre , Degos Jean‐Denis , Peschanski Marc , Lisovoski Fabrice
Published: December 2002

Assessment programs recently designed to follow‐up patients with Huntington's disease (HD) in therapeutic trials have not included electrophysiological testing in the list of mandatory examinations. This omission is likely due to the current lack of data establishing a clear correlation between the electrophysiological results and those of clinical assessment. We address this issue in a cohort of 36 patients at relatively early stages of the disease (I and II). Electrophysiological studies comprised the recording of palmar sympathetic skin responses (SSRs), blink reflexes (BRs), thenar long latency reflexes (LLRs), cortical somatosensory evoked potentials (SEPs), and electromyographic silent periods evoked by transcranial magnetic stimulation (SPs). Results were analyzed with reference to disease duration and staging and to specific cognitive, psychiatric, and motor alteration. SEPs were the most and very sensitive markers, because they were abnormal in 94% of patients. Except for LLRs, alteration of electrophysiological results increased in parallel to the evolution of the disease. Except for LLRs and SSR latency, electrophysiological results correlated with those of specific clinical examinations. In particular, an increased BR latency or a reduced amplitude of the N20 component of SEPs correlated with the extent of bradykinesia, whereas a reduced amplitude of SSRs or of the N30 component of SEPs correlated with hyperkinesia. Overall, electrophysiological tests, in particular SEPs and BRs, appeared sensitive and interesting in the follow‐up of HD patients and correlated with various clinical parameters, suggesting that these easy to perform and noninvasive repeatable examinations could be added fruitfully to the assessment programs for HD. © 2002 Movement Disorder Society
Parkinson's disease and dementia with Lewy bodies: One disease or two?
Authors: Richard Irene Hegeman , Papka Michelle , Rubio Ana , Kurlan Roger
Published: December 2002

Parkinson's disease (PD) and dementia with Lewy bodies (DLB) have clinical features in common and are both characterized neuropathologically by the presence of Lewy bodies (LBs). We conducted a clinicopathological correlation pilot study to better understand whether PD and DLB represent two distinct nosological entities or rather exist along the spectrum of a single LB disease. A neuropathologist blinded to clinical diagnoses evaluated brains with largely pure LB pathology to determine LB distribution and frequency. Research clinicians blinded to LB distribution and frequency determined consensus clinical diagnoses. Clinical features separated cases into two groups, one having features most compatible with PD and the other with DLB. The groups were distinguishable mainly by the time course of clinical symptoms. Although the presence of neocortical LBs was more common in the group of patients with clinical features of DLB, neocortical LBs were also present in 1 member of the PD group and even in the clinically normal control subject. Thus, there appear to be two clinical syndromes, distinguished mainly by the time course of symptoms. The mechanisms responsible for the different clinical presentations are not known, and the issue of whether PD and DLB represent two distinct diseases remains unsettled. © 2002 Movement Disorder Society
Practice effects in three‐dimensional sequential rapid aiming in Parkinson's disease
Authors: Smiley‐Oyen Ann L. , Worringham Charles J. , Cross Carol L.
Published: December 2002

One hypothesized role of the basal ganglia, based largely on findings in Parkinson's disease (PD) patients, is the control of movement sequences. We examined changes in performance with practice of a movement sequence in PD patients and age‐matched controls (n = 8 per group). Subjects practiced a complex three‐dimensional sequential aiming task over 2 days, completing 180 trials, with the goal to minimize response time within specified accuracy limits. The results indicated that both groups became faster in planning the movement, and both groups moved more quickly through the sequence with practice. The PD group's decrease in movement time occurred primarily within the first 45 trials, whereas the control group continued to improve through the first 150 trials. Flight time (time between targets) to a small target decreased with practice in both groups, but flight time to a large target decreased only in the control group. This finding indicates that error corrective processes are more amenable to practice than ballistic processes in people with PD. There was little evidence that either group improved their performance by planning shorter (lower) trajectories, but rather increased mean velocity. Contact time (time on target) decreased with practice in both groups, and there were no group differences. These data indicate that practice can improve performance, both in planning and in specific execution processes. © 2002 Movement Disorder Society
Memory and executive function impairment predict dementia in Parkinson's disease
Authors: Levy Gilberto , Jacobs Diane M. , Tang Ming‐Xin , Côté Lucien J. , Louis Elan D. , Alfaro Brenda , Mejia Helen , Stern Yaakov , Marder Karen
Published: December 2002

We analyzed the association of neuropsychological test impairment at baseline with the development of dementia in idiopathic Parkinson's disease (PD) patients. A cohort of nondemented PD patients from northern Manhattan, NY was followed annually with neurological and neuropsychological evaluations. The neuropsychological battery included tests of verbal and nonverbal memory, orientation, visuospatial ability, language, and abstract reasoning. The association of baseline neuropsychological tests scores with incident dementia was analyzed using Cox proportional hazards models. The analysis controlled for age, gender, education, duration of PD, and the total Unified Parkinson's Disease Rating Scale motor score at baseline. Forty‐five out of 164 patients (27%) became demented during a mean follow‐up of 3.7 ± 2.3 years. Four neuropsychological test scores were significantly associated with incident dementia in the Cox model: total immediate recall (RR: 0.92, 95% CI: 0.87–0.97, P = 0.001) and delayed recall (RR: 0.73, 95% CI: 0.59–0.91, P = 0.005) of the Selective Reminding Test (SRT), letter fluency (RR: 0.87, 95% CI: 0.77–0.99, P = 0.03), and Identities and Oddities of the Mattis Dementia Rating Scale (RR: 0.85, 95% CI: 0.73–0.98, P = 0.03). When the analysis was performed excluding patients with a clinical dementia rating of 0.5 (questionable dementia) at baseline evaluation, total immediate recall and delayed recall were still predictive of dementia in PD. Our results indicate that impairment in verbal memory and executive function are associated with the development of dementia in patients with PD. © 2002 Movement Disorder Society
Clozapine withdrawal symptoms in a Parkinson's disease patient
Authors: Zesiewicz Theresa A. , Borra Sujatha , Hauser Robert A.
Published: December 2002

Abrupt clozapine withdrawal can cause rebound psychosis and severe somatic symptoms in psychiatric patients. We report on the case of an advanced Parkinson's disease patient who developed myoclonus, tremor, rigidity, hyperreflexia, and stupor after abrupt clozapine withdrawal. The patient's symptoms resolved with treatment with cyproheptadine. This clinical picture suggests serotonergic rebound as an explanation for the patient's symptoms, although other pharmacological mechanisms are possible. Clozapine should be gradually withdrawn over a period of 1 to 2 weeks when possible, and abruptly discontinued only when necessary. © 2002 Movement Disorder Society
Application of the International Cooperative Ataxia Scale rating in multiple system atrophy
Authors: Tison François , Yekhlef Farid , Balestre Eric , Chrysostome Virginie , Quinn Niall , Wenning Gregor K. , Poewe Werner
Published: December 2002

We assessed the International Cooperative Ataxia Scale (ICARS) as a means of extracting and rating cerebellar signs in multiple system atrophy (MSA). Cross‐sectional analysis of internal consistency, factor structure, and correlation with parkinsonism severity (Unified Parkinson's Disease Rating Scale [UPDRS] III) of the ICARS, in 50 unselected MSA patients (mean age, 67.6 years; mean disease duration, 5.5 years), 50 age‐matched and disease duration‐matched Parkinson' disease (PD) patients, and 50 control subjects. Fifteen patients (30%) had MSA‐C (cerebellar subtype) and 35 (70%) MSA‐P (parkinsonism subtype), and 66% had at least one cerebellar sign. The total ICARS score was much higher (fivefold) in MSA compared to PD patients. The ICARS score was twofold higher in MSA‐C than in MSA‐P patients. MSA‐C patients had a higher score than MSA‐P mainly on posture and gait disturbances and kinetic functions subscores. All the ICARS items were significantly more severe in MSA than in PD patients, who in turn scored higher than the controls. In MSA, internal consistency was excellent (Cronbach = 0.93). Factor structure analysis revealed four clinically distinct subscores, in accordance with the scale structure, which accounted for 70% of the variance. The ICARS showed less consistency and accuracy in PD patients; however, the ICARS scores significantly correlated with the UPDRS‐III scores in both MSA and PD patients. The ICARS appears a useful tool to extract and rate the severity of cerebellar signs in MSA; however, it is clearly contaminated by parkinsonian features. © 2002 Movement Disorder Society
A method for measuring cerebral glucose metabolism in vivo by 13C‐NMR spectroscopy
Authors: Cohen David M. , Wei Jingna , O'Brian Smith E. , Gao Xiaolian , Quast Michael J. , Sokoloff Louis
Published: December 2002

Current methods for estimating the rate of cerebral glucose utilization (CMRglc) typically measure metabolic activity for 40 min or longer subsequent to administration of [13C]glucose, 2‐[14C]deoxyglucose, or 2‐[18F]deoxyglucose. We report preliminary findings on estimating CMRglc for a period of 15 min by use of 2‐[6‐13C]deoxyglucose. After a 24‐hr fast, rats were anesthetized, infused with [1‐13C]glucose for 50 min, and injected with 2‐[6‐13C]deoxyglucose (500 mg/kg). During the subsequent 12.95 min the estimated value of CMRglc was 0.6 ± 0.4 micromol/min/g (mean ± SD, N = 7), in agreement with values reported for anesthetized rats studied with the 2‐[14C]deoxyglucose method and other 13C‐NMR methods that measure CMRglc. In rats injected with bicuculline methiodide (a known stimulant of CMRglc), CMRglc increased by more than 75% during 12.95 min following injection of bicuculline (Wilcoxon signed rank test, P = 0.042, N = 8). Magn Reson Med 48:1063–1067, 2002. © 2002 Wiley‐Liss, Inc.
Magnetization structure contrast based on intermolecular multiple‐quantum coherences
Authors: Bouchard Louis‐Serge , Rizi Rahim R. , Warren Warren S.
Published: December 2002

In vivo and ex vivo MRI based on intermolecular multiple‐quantum coherences (iMQC) is predicted to provide a fundamentally different source of contrast for MRI. This article investigates the dependence of image contrast upon the choice of correlation distance for a heterogeneous material. A closely packed array of parallel hollow cylinders was used to demonstrate signal intensity variations when the correlation distance becomes comparable to the gap size between the cylinders. The observed effects agree well with three‐dimensional calculations of the time evolution of magnetization under the nonlinear Bloch equations. Magn Reson Med 48:973–979, 2002. © 2002 Wiley‐Liss, Inc.
Mapping of the B1 field distribution of a surface coil resonator using EPR imaging
Authors: He Guanglong , Evalappan Sathesh P. , Hirata Hiroshi , Deng Yuanmu , Petryakov Sergey , Kuppusamy Periannan , Zweier Jay L.
Published: December 2002

Surface coil resonators have been widely used to perform topical EPR spectroscopy. They are usually positioned adjacent to or implanted within the body. For EPR applications these resonators have a number of important advantages over other resonator designs due to their ease of sample accessibility, mechanical fabrication, implementation of electronic tuning and coupling functions, and low susceptibility to sample motions. However, a disadvantage is their B1 field inhomogeneity, which limits their usefulness for 3D imaging applications. We show that this problem can be addressed by mapping and correcting the B1 field distribution. We report the use of EPR imaging (EPRI) to map the B1 distribution of a surface coil resonator. We show that EPRI provides a fast, accurate, and reliable technique to evaluate the B1 distribution. 3D EPRI was performed on phantoms, prepared using three different saline concentrations, to obtain the B1 distribution. The information obtained from the phantoms was used to correct the images of living animals. With the use of this B1 correction technique, surface coil resonators can be applied to perform 3D mapping of the distribution of free radicals in biological samples and living systems. Magn Reson Med 48:1057–1062, 2002. © 2002 Wiley‐Liss, Inc.
Application of sensitivity‐encoded echo‐planar imaging for blood oxygen level‐dependent functional brain imaging †
Authors: de Zwart Jacco A. , van Gelderen Peter , Kellman Peter , Duyn Jeff H.
Published: December 2002

The benefits of sensitivity‐encoded (SENSE) echo‐planar imaging (EPI) for functional MRI (fMRI) based on blood oxygen level‐dependent (BOLD) contrast were quantitatively investigated at 1.5 T. For experiments with 3.4 × 3.4 × 4.0 mm3 resolution, SENSE allowed the single‐shot EPI image acquisition duration to be shortened from 24.1 to 12.4 ms, resulting in a reduced sensitivity to geometric distortions and T blurring. Finger‐tapping fMRI experiments, performed on eight normal volunteers, showed an overall 18% loss in t‐score in the activated area, which was substantially smaller than expected based on the image signal‐to‐noise ratio (SNR) and g‐factor, but similar to the loss predicted by a model that takes physiologic noise into account. Magn Reson Med 48:1011–1020, 2002. Published 2002 Wiley‐Liss, Inc.
Phased array ghost elimination (PAGE) for segmented SSFP imaging with interrupted steady‐state
Authors: Kellman Peter , Guttman Michael A. , Herzka Daniel A. , McVeigh Elliot R.
Published: December 2002

Steady‐state free precession (SSFP) has recently proven to be valuable for cardiac imaging due to its high signal‐to‐noise ratio and blood‐myocardium contrast. Data acquired using ECG‐triggered, segmented sequences during the approach to steady‐state, or return to steady‐state after interruption, may have ghost artifacts due to periodic k‐space distortion. Schemes involving several preparatory RF pulses have been proposed to restore steady‐state, but these consume imaging time during early systole. Alternatively, the phased‐array ghost elimination (PAGE) method may be used to remove ghost artifacts from the first several frames. PAGE was demonstrated for cardiac cine SSFP imaging with interrupted steady‐state using a simple alpha/2 magnetization preparation and storage scheme and a spatial tagging preparation. Magn Reson Med 48:1076–1080, 2002. Published 2002 Wiley‐Liss, Inc.
RF heating due to conductive wires during MRI depends on the phase distribution of the transmit field
Authors: Yeung Christopher J. , Susil Robert C. , Atalar Ergin
Published: December 2002

In many studies concerning wire heating during MR imaging, a “resonant wire length” that maximizes RF heating is determined. This may lead to the nonintuitive conclusion that adding more wire, so as to avoid this resonant length, will actually improve heating safety. Through a theoretical analysis using the method of moments, we show that this behavior depends on the phase distribution of the RF transmit field. If the RF transmit field has linear phase, with slope equal to the real part of the wavenumber in the tissue, long wires always heat more than short wires. In order to characterize the intrinsic safety of a device without reference to a specific body coil design, this maximum‐tip heating phase distribution must be considered. Finally, adjusting the phase distribution of the electric field generated by an RF transmit coil may lead to an “implant‐friendly” coil design. Magn Reson Med 48:1096–1098, 2002. © 2002 Wiley‐Liss, Inc.
Interleaved pulsed MAMBA: A new parallel slice imaging method
Authors: Paley Martyn N.J. , Lee Kuan J. , Wild James M. , Whitby Elspeth H. , Griffiths Paul D.
Published: December 2002

A method of acquiring slices in parallel is described which uses interleaved sets of pulsed B0 field coils to generate discrete regions of uniform field within the main magnetic field known as interleaved MAMBA (multiple acquisition micro B0 array). Simulations of a number of coil designs were performed using the Biot‐Savart law. A six‐step coil was built and interfaced to a 0.17 T Niche MRI system and the field steps measured using an imaging technique. Measured field steps were in good agreement with the values predicted by simulation. The coil design was then scaled up by a factor of three, interfaced to a 1.5 T whole‐body MRI system, and scans of the hands and arms of volunteers were acquired from up to four field steps using standard spin and gradient echo sequences. Images were also acquired simultaneously from two field steps with no frequency encode aliasing and one excitation. The one‐dimensional interleaved pulsed MAMBA step field technique shows great promise for enabling many slices to be acquired simultaneously along the axis of the coil for rapid volumetric studies without the need for multiple shot Hadamard encoding. Extension of interleaved coil design to two or three dimensions is feasible, which could provide full spatial coverage combined with ultra‐rapid data acquisition. Magn Reson Med 48:1043–1050, 2002. © 2002 Wiley‐Liss, Inc.
Magnetic resonance relaxivity of dendrimer‐linked nitroxides
Authors: Winalski Carl S. , Shortkroff Sonya , Mulkern Robert V. , Schneider Erika , Rosen Gerald M.
Published: December 2002

The relaxivity and bioreduction rates of eight dendrimer‐linked nitroxides varying in the number of nitroxides per molecule were measured and the potential use of these compounds as MR contrast agents was demonstrated. The T1 and T2 relaxivities, measured at room temperature and 1.5 T, varied linearly with the number of nitroxides per molecule for compounds with up to 16 nitroxides per molecule. Fourth‐generation polypropylenimide‐ (DAB) and third‐generation polyamidoamine‐ (PAMAM) dendrimer‐linked nitroxides were found to have greater relaxivity than gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). The greater number of nitroxides per dendrimer increased relaxivity over that of a single nitroxide, allowing a decreased dose to achieve differential contrast with MR evaluations. Rates of nitroxide bioreduction were below detection threshold using EPR spectroscopy for generation 2 dendrimers and higher. A pilot assessment of in vivo cartilage uptake that compared intraarticular injection of three structurally different dendrimer‐linked nitroxides with Gd‐DTPA and with saline demonstrated high affinity of the DAB‐dendrimer‐linked nitroxides for normal rabbit articular cartilage. From these results, it is evident that target‐specific dendrimer‐linked nitroxides can be designed. Magn Reson Med 48:965–972, 2002. © 2002 Wiley‐Liss, Inc.
Anomalous nuclear magnetic relaxation of aqueous solutions of ferritin: An unprecedented first‐order mechanism
Authors: Gossuin Yves , Roch Alain , Muller Robert N. , Gillis Pierre , Lo Bue Francesco
Published: December 2002

Ferritin, the iron‐storing protein, speeds up proton transverse magnetic relaxation in aqueous solutions. This T2 shortening is used in MRI to quantify iron in the brain and liver. Current theoretical models underestimate the relaxation enhancement by ferritin at imaging fields, and they do not predict the measured dependence of the rate enhancement on the magnetization of the particles. Here it is shown that a proton exchange dephasing model (PEDM) overcomes these limitations by allowing a first‐order relaxation mechanism. The PEDM considers proton exchange between bulk water and exchangeable protons located at the surface of the hydrated iron oxide nanometric core of the protein. Relaxation is shown to depend on the distribution of the frequency shifts of the adsorption sites; the observed properties agree with a Lorentzian distribution. Computer simulations utilizing recent Mössbauer spectroscopy data show that the distribution of these shifts is effectively Lorentzian. Magn Reson Med 48:959–964, 2002. © 2002 Wiley‐Liss, Inc.
How does blood oxygen level‐dependent (BOLD) contrast correlate with oxygen partial pressure (pO2) inside tumors?
Authors: Baudelet Christine , Gallez Bernard
Published: December 2002

Blood oxygen level‐dependent (BOLD) contrast‐based functional MRI (fMRI) has been reported as a method to assess the evolution of tumor oxygenation after hyperoxic treatments, because of its sensitivity to changes in blood flow and deoxyhemoglobin content. However a number of questions remain: 1) In view of tumor heterogeneity, how good is the correlation between the MR parameters in gradient‐echo imaging (signal intensity (SI) or effective transverse relaxation time (T)) and local tumor oxygen partial pressure (pO2)? 2) Is the magnitude of the change in SI or T a quantitative marker for variation in pO2? 3) Is initial T a good marker for initial pO2? To address these questions, murine tumors were imaged during respiratory challenges at 4.7 Tesla, using fiber‐optic microprobes to simultaneously acquire tumor pO2 and erythrocyte flux. The BOLD signal response (SI and T) was temporally correlated with changes in pO2. However, the magnitude of the signal bore no absolute relation to pO2 across tumors, i.e., a given change in SI corresponded to a 25 mmHg pO2 change in one tumor, but to a 100 mmHg change in another. The initial T value did not reliably predict tumor oxygenation at the beginning of the experiment. In conclusion, the major advantages of the technique include noninvasiveness, high spatial resolution, and real‐time detection of pO2 fluctuations. Information afforded by the BOLD imaging technique is qualitative in nature and may be combined with other techniques capable of providing an absolute measure of pO2. Magn Reson Med 48:980–986, 2002. © 2002 Wiley‐Liss, Inc.