bluuebunny/crossref_metadata_2025 huggingface dataset:
Employment of persons with disabilities in information technology jobs: literature review for “IT works”
Authors: Schartz Kevin , Schartz Helen A. , Blanck Peter
Published: December 2002

This article reviews relevant literature as to the labor pool of qualified individuals with disabilities and employment in information technology (IT) sector jobs. First, the article reviews the empirical literature on barriers to employment in IT for persons with disabilities. The examination then is extended to studies of barriers to employment for individuals with disabilities in other employment sectors. Findings illustrate the limited experiences that IT and non‐IT companies have in employing and accommodating employees with disabilities. Implications are discussed for enhancing the employment of qualified workers with disabilities in IT through research, education, training, and mentoring programs. Copyright © 2002 John Wiley & Sons, Ltd.
Applicability of the ADA to “Ticket to Work” employment networks
Authors: Blanck Peter , Clay Lisa , Schmeling James , Morris Michael , Ritchie Heather
Published: December 2002

This article examines the applicability of the antidiscrimination provisions of the Americans with Disabilities Act (ADA) of 1990 to The Ticket to Work and Work Incentives Improvement Act (TWWIIA) passed in 1999. Among other policy changes, under the Ticket to Work program, eligible recipients of disability insurance (SSDI) and supplemental income (SSI) receive a voucher or “ticket” to obtain services from qualified employment networks (ENs). ENs provide employment services and supports to designated beneficiaries and must meet certain qualification requirements. The ADA is applicable to ENs in several ways: primarily, in the EN's responsibility to provide appropriate access and services to program participants. This article discusses application of the ADA to the Ticket Program as ENs begin to serve program beneficiaries. Copyright © 2002 John Wiley & Sons, Ltd.
Violence against women: is psychology part of the problem or the solution? A content analysis of psychological research from 1990 through 1999
Authors: Salazar Laura F. , Cook Sarah L.
Published: December 2002

Previous critiques of traditional psychology portrayed a discipline that examines social problems from an exceptionalistic perspective and decontextualizes the subjects of its inquiries. We analysed 10 years of psychological research on domestic violence, sexual assault, and sexual harassment to determine whether this criticism applied to violence against women research. Specifically, we examined the purpose, level of analysis, sample, and context of 1396 PsychLit abstracts. We found that almost half reported an examination of causal factors. Only one quarter reported intervention studies. Most studies focused at the individual level of analysis and few included contextual factors. Investigators explored questions about domestic violence most frequently among samples of victims and perpetrators drawn from clinical settings. Sexual assault and sexual harassment researchers depended on victims and perpetrators to a lesser extent, but tended to rely upon convenience samples from college settings. Representative community samples were used in only 9% of studies. These findings support the view that psychological research on violence against women suffers from a heavy emphasis on exceptionalism at the expense of a universalistic perspective, the latter of which we contend is critical to advancing the field and reducing a major threat to women's health and wellbeing. Copyright © 2002 John Wiley & Sons, Ltd.
Xath5 regulates neurogenesis in the Xenopus olfactory placode
Authors: Burns Carole J. , Vetter Monica L.
Published: December 2002

Helix‐loop‐helix (HLH) genes function as important regulators of neurogenesis in both the peripheral and central nervous systems. The olfactory system is an ideal tissue in which to study the role of these genes in regulating the acquisition of neuronal cell fate, particularly that of the olfactory receptor neuron (ORN). Here we describe the expression of several basic HLH (bHLH) and repeat HLH (rHLH) factors during olfactory placode development in Xenopus laevis. Our work reveals that a combination of both bHLH and rHLH genes are sequentially expressed within the nascent olfactory placode during normal development. Moreover, overexpression of the bHLH factor, Xenopus atonal homologue 5 (Xath5), promotes olfactory neural fate independent of cellular proliferation within a restricted domain at the anterior of the embryo. Collectively, our data argue that HLH genes are expressed in a cascade during olfactory placode development and that the activity of an atonal homologue, Xath5, can promote ORN fate but only in the appropriate developmental context. © 2002 Wiley‐Liss, Inc.
Expression of Brachyury during development of the dendrobatid frog Colostethus machalilla
Authors: Benítez María‐Soledad , Del Pino Eugenia M.
Published: December 2002

The expression of Brachyury (Bra) during development of Colostethus machalilla was analyzed with a polyclonal antibody. The observed molecular mass of Bra was of 48 kDa, as in Xenopus laevis. During cleavage, low levels of Bra were expressed. In contrast, in the blastula Bra became up‐regulated, and Bra protein was present in a wide ring of surface cells. The surface expression of Bra disappeared in the gastrula, and a new ring of Bra‐positive nuclei was detected in deep cells around the closing blastopore. The C. machalilla external and internal rings of Bra‐positive nuclei apparently mark the prospective mesoderm in the blastula and gastrula, respectively. The two Bra expression rings were dissociated in time in the fairly slow developing embryos of this frog. Brachyury expression in the notochord became visible only after the blastopore closed, in contrast with X. laevis. In addition, Bra expression in the notochord indicated that dorsal convergence and extension occurred after blastopore closure. The C. machalilla Bra‐positive notochord was originally exposed on the gastrocoel roof, in agreement with a superficial component of the prospective mesoderm. © 2002 Wiley‐Liss, Inc.
Activation of microglia: A neuroinflammatory role for CAP37
Authors: Pereira H. Anne , Ruan Xin , Kumar Padmasini
Published: December 2002

Recent evidence suggests that inflammation and immune function in the central nervous system (CNS) may play a considerable role in the progression of many neurodegenerative diseases. It is known that microglia, the CNS equivalent of peripheral blood monocytes, may be instrumental in causing neurotoxicity. However, the mediator(s) that activates microglia to produce toxic substances that orchestrate cell death has yet to be elucidated. We have identified a novel inflammatory molecule, cationic antimicrobial protein of molecular weight 37 kDa (CAP37), to the brains of patients dying from Alzheimer's disease. CAP37 is known to be a potent activator and regulator of monocyte function in the systemic circulation. We hypothesize that CAP37, a mediator previously shown to recruit and activate monocytes in the systemic circulation, may also play a role in CNS inflammation by modulating microglial function. Here we demonstrate that CAP37 is a chemoattractant for microglia and that CAP37‐treated microglia express class II major histocompatibility antigens and produce proinflammatory cytokines and chemokines. We conclude that CAP37 has the ability to activate microglial cells and suggest that it has the potential to serve as a neuroinflammatory molecule. GLIA 41:64–72, 2003. © 2003 Wiley‐Liss, Inc.
Role of enteric glial cells in inflammatory bowel disease
Authors: Cabarrocas Julie , Savidge Tor C. , Liblau Roland S.
Published: December 2002

Enteric glial cells (EGCs) represent an extensive but relatively poorly described cell population within the gastrointestinal tract. Accumulating data suggest that EGCs represent the morphological and functional equivalent of CNS astrocytes within the enteric nervous system (ENS). The EGC network has trophic and protective functions toward enteric neurons and is fully implicated in the integration and the modulation of neuronal activities. Moreover, EGCs seem to be active elements of the ENS during intestinal inflammatory and immune responses, sharing with astrocytes the ability to act as antigen‐presenting cells and interacting with the mucosal immune system via the expression of cytokines and cytokine receptors. Transgenic mouse systems have demonstrated that specific ablation of EGC by chemical ablation or autoimmune T‐cell targeting induces an intestinal pathology that shows similarities to the early intestinal immunopathology of Crohn's disease. EGCs may also share with astrocytes the ability to regulate tissue integrity, thereby postulating that similar interactions to those observed for the blood‐brain barrier may also be partly responsible for regulating mucosal and vascular permeability in the gastrointestinal tract. Disruption of the EGC network in Crohn's disease patients may represent one possible cause for the enhanced mucosal permeability state and vascular dysfunction that are thought to favor mucosal inflammation. GLIA 41:81–93, 2003. © 2003 Wiley‐Liss, Inc.
Formation of a β1 integrin signaling complex in Schwann cells is independent of rho
Authors: Taylor Anna R. , Geden Sandra E. , Fernandez‐Valle Cristina
Published: December 2002

Schwann cell adhesion to basal lamina is essential for peripheral nerve development. β1 integrin receptors for extracellular matrix cooperate with other receptors to transmit signals that coordinate cell cycle progression and initiation of differentiation, including myelin‐specific gene expression. In Schwann cell/sensory neuron cocultures, β1 integrins complex with focal adhesion kinase (FAK), fyn kinase, paxillin, and schwannomin in response to basal lamina adhesion. To study the assembly of this signaling complex in Schwann cells (SCs), we induced β1 integrin clustering on suspended cells using an immobilized antibody and recovered a complex containing β1 integrin, FAK, paxillin, and schwannomin. In adherent subconfluent cells, the proteins colocalized to filopodia, ruffling membranes and focal contacts. We assessed the role of rhoGTPase in the process of integrin complex assembly by introducing C3 transferase (C3T), a rho inhibitor, into the cells. Although C3T caused dose‐dependent morphological abnormalities, FAK, paxillin, and schwannomin were able to coimmunoprecipitate with β1 integrin. Additionally, colocalization of FAK, paxillin, and schwannomin with β1 integrin in filopodia and small focal contacts remained unchanged. We conclude that SCs do not require active rho to recruit signaling and structural proteins to β1 integrins clustered at the plasma membrane. Rho is required to establish large focal adhesions and to spread and stabilize plasma membrane extensions. GLIA 41:94–104, 2003. © 2003 Wiley‐Liss, Inc.
Coexistence of serotonin 3 (5‐HT3) and CB1 cannabinoid receptors in interneurons of hippocampus and dentate gyrus
Authors: Morales Marisela , Bäckman Cristina
Published: December 2002

Using in situ hybridization histochemistry, a high degree of coexpression of the functional 5‐HT3A subunit of the 5‐HT3 receptor and the central CB1 cannabinoid receptor was detected in all subfields of the hippocampus and subgranular layer of the dentate gyrus (DG). Semiquantitative analysis demonstrated that, depending on the hippocampal layer, 72–88% of CB1‐expressing interneurons coexpress the 5‐HT3A subunit. Within the DG, 5‐HT3A/CB1 double‐labeled neurons were confined to the subgranular layer, where close to 80% of all CB1‐expressing basket neurons were found to contain 5‐HT3A subunit transcripts. These results provide the first evidence indicating that the only ion channel receptor for serotonin and central CB1 cannabinoid receptor coexist in neurons containing the inhibitory neurotransmitter γ‐aminobutyric acid (GABA). These findings suggest possible interactions between the cannabinoid and serotonergic systems at the level of GABA neurotransmission. However, activation of 5‐HT3‐ or CB1‐receptors are likely to have opposing regulatory effects on GABA neurotransmission, as 5‐HT3 receptor activation by serotonin results in the release of GABA, while CB1 activation by cannabinoids results in inhibition of GABA release. Hippocampus 2002;12:756–764. © 2002 Wiley‐Liss, Inc.
Trans‐synaptic increase of hypoxic tolerance in hippocampus upon physical challenge with two‐photon microscopy
Authors: Büchner Maren , Huber Roman , Riepe Matthias W.
Published: December 2002

Neuronal hypoxic tolerance is modulated by preceding challenges. We investigated hypoxic tolerance in CA1 pyramidal cells of murine hippocampal slices upon preceding physical challenge with two‐photon illumination in close spatial proximity to the recorded area, at distant presynaptic neurons, or preceding chemical treatment with acetylsalicylic acid while zinc fluorescence was assessed with fluorescence measurement upon staining with N‐(6‐methoxy‐8‐quinolyl)‐para‐toluenesulfonamide (TSQ). Posthypoxic recovery (15 min hypoxia, 45 min recovery) of CA1 population spike amplitude (PSAP) upon stimulation of Schaffer collaterals in hippocampal region CA3 was 20 ± 38% (mean ±SD; n = 15) in control slices. At the end of hypoxia, zinc fluorescence increased to 120 ± 16% (P < 0.05 to control) in slices that later recovered and 141 ± 20% in slices that did not recover (P < 0.01 to control; P < 0.05 compared with returns). Multi‐photon illumination alone was an appropriate physical challenge to improve hypoxic tolerance, even trans‐synaptically. Depending on the number of illuminations posthypoxic PSAP increased up to 84 ± 25% (P < 0.01 to control) upon illumination of hippocampal region CA1 and 85 ± 28% (P < 0.01 to control) upon illumination of CA3. With the latter treatment, zinc fluorescence in CA1 increased to 126 ± 20% before hypoxia (P < 0.05 to control), and no further zinc increase was observed upon subsequent hypoxia. Similar results were obtained upon chemical preconditioning with acetylsalicylate. We conclude that observation of live specimen with multi‐photon imaging alters the physiology of neuronal cell ensembles, including hypoxic tolerance, even trans‐synaptically at long distances from the imaged area. This is mediated in part through endogenous modulation by zinc. Mild zinc increase improves hypoxic tolerance while pronounced increase predicts neuronal cell death. Hippocampus 2002;12:765–773. © 2002 Wiley‐Liss, Inc.
Posttraining but not pretraining lesions of the hippocampus interfere with feature‐negative discrimination of fear‐potentiated startle
Authors: Heldt Scott A. , Coover Gary D. , Falls William A.
Published: December 2002

Previous studies have suggested that the hippocampus may play an important role in some forms of inhibitory learning. The goal of the present study was to assess whether the hippocampus is also important for inhibition of fear acquired after serial feature‐negative discrimination training. Rats were given aspiration lesions of the hippocampus either before or after training in which a target light was paired with shock when presented alone, but not paired with shock when presented in serial compound with a noise feature (light+/noise→light−). Conditioned fear to the target stimulus and feature‐target compound were measured with fear‐potentiated startle. Pretraining lesion of the hippocampus did not disrupt feature‐negative discrimination performance relative to sham‐operated and cortical lesioned controls. In contrast, hippocampal lesions performed after training severely disrupted performance. Specifically, rats with hippocampal lesions failed to inhibit fear when the noise feature was presented in compound with the target. However, these rats could reacquire the feature‐negative discrimination. These observations suggest that the hippocampus may normally be involved in retention or retrieval of serial feature‐negative discrimination; however, in its absence feature‐negative discrimination can still be acquired. Hippocampus 2002;12:774–786. © 2002 Wiley‐Liss, Inc.
Identification of differentially expressed genes in immortalized human bronchial epithelial cell line as a model for in vitro study of lung carcinogenesis
Authors: An Qian , Pacyna‐Gengelbach Manuela , Schlüns Karsten , Deutschmann Nicole , Guo Suping , Gao Yanning , Zhang Jianjun , Cheng Shujun , Petersen Iver
Published: December 2002

Suppression subtractive hybridization (SSH) was applied to identify differentially expressed genes in the SV40LT immortalized human bronchial epithelial cell line Y‐BE, with normal human bronchial epithelial cells (HBEC) as a control. Two cDNA libraries of up‐ and downregulated genes were generated, comprising 218 known genes and 131 unknown genes in total. The expression of 22 clones from the 2 libraries was investigated by Northern blot analysis, and 86.4% (19/22) of them showed differential expression between Y‐BE cells and HBEC. Although the Y‐BE cells are nontumorigenic in nude mice, Comparative genomic hybridization (CGH) detected some DNA imbalances in Y‐BE cells that were similar to lung cancer cells. Our data demonstrate that the studied cell line Y‐BE and SSH is a reliable approach for identifying new genes that are associated with immortalization and early tumor development that may help to understand the pathogenesis of lung cancer. © 2002 Wiley‐Liss, Inc.
EMDR and the role of the clinician in psychotherapy evaluation: Towards a more comprehensive integration of science and practice
Authors: Shapiro Francine
Published: December 2002

Eye Movement Desensitization and Reprocessing (EMDR) is an integrative psychotherapy approach that has been consistently evaluated as efficacious in the treatment of posttraumatic stress disorder (PTSD). The information processing model that guides its clinical application posits that EMDR should be effective in treating other psychological disorders that have experiential contributors. Research is needed to assess such applications. This special issue features three case series in which EMDR was applied to the treatment of complex PTSD, phobias, and chronic pain, respectively. The authors discuss deficits in the research literature, provide preliminary data on EMDR treatment of these conditions, and offer descriptive guidelines for evaluation that are achievable by the practicing clinician. Two additional articles offer preliminary data on physiological and cognitive/affective concomitants of therapeutic change. It is argued that clinicians should play a greater role in the rigorous and extensive examination of psychological treatments in the context of the exigencies of clinical practice. © 2002 Wiley Periodicals, Inc. J Clin Psychol 58: 1453–1463, 2002.
Diagnosing multiple system atrophy with greater accuracy: Combined analysis of the clonidine–growth hormone test and external anal sphincter electromyography
Authors: Lee Eun Ah , Kim B. Joon , Lee Won Yong
Published: December 2002

The clonidine–growth hormone test (CGHT) has been proposed as a means of differentiating multiple system atrophy (MSA) from idiopathic Parkinson's disease (PD). However, it is controversial whether the CGHT is valid. We sought to confirm the validity of the CGHT and to compare the diagnostic accuracy of the CGHT with that of external anal sphincter electromyelography (Sph‐EMG) for MSA. We performed the CGHT and the Sph‐EMG on 21 PD patients, 23 patients with probable MSA of parkinsonian type (MSA‐p), and 22 patients with probable MSA of cerebellar type (MSA‐c). We compared the sensitivity, specificity, and positive and negative predictive values (PPV and NPV) of CGHT, Sph‐EMG, and a combination of the two tests. We also evaluated the correlations of Unified Parkinson's Disease Rating Scale (UPDRS) scores with the results of the two tests. There was no significant difference between the UPDRS scores for the PD and MSA‐p groups. Serum growth hormone concentrations after clonidine significantly increased in PD (mean increase ± SEM, 4.19 ± 0.92 ng/ml; P < 0.0001), but remained unchanged in both MSA‐p (0.83 ± 0.61 ng/ml) and MSA‐c (1.45 ± 0.58 ng/ml). The growth hormone responses to clonidine in MSA‐p were significantly different from those in PD (P < 0.05). Abnormal, denervated Sph‐EMG was observed in 95.7% of MSA‐p, 86.4% of MSA‐c, and 33.3% of PD patients. Compared to Sph‐EMG, the CGHT was less sensitive but more specific in both MSA‐p and MSA‐c. The result of neither test correlated with the severity of parkinsonism. Interestingly, combining the results of the CGHT and Sph‐EMG markedly increased the specificity (85.7% in the CGHT and 66.7% in Sph‐EMG vs. 95.2% in the combination study) and the PPV in both MSA‐p (85.7% and 75.9% vs. 94.4%) and MSA‐c (82.4% and 73.1% vs. 91.7%). We confirm that the CGHT can distinguish MSA‐p from PD. Its sensitivity is lower and its specificity higher than Sph‐EMG. Compared to either test alone, combined testing with the CGHT and Sph‐EMG increased specificity and PPV, thereby enhancing accuracy in the diagnosis of MSA. © 2002 Movement Disorder Society
Hemichorea as an initial manifestation of moyamoya disease: Reversible striatal hypoperfusion demonstrated on single photon emission computed tomography
Authors: Hong Yoon‐Ho , Ahn Tae‐Beom , Oh Chang Wan , Jeon Beom S.
Published: December 2002

We describe a case with unilateral moyamoya disease that showed progressive hemichorea as an initial manifestation. Single photon emission computed tomography showed perfusion defect in the contralateral basal ganglia although magnetic resonance imaging was unremarkable. Hemichorea improved along with normalization of perfusion after bypass surgery, suggestive of striatal hypoperfusion as the cause of hemichorea. © 2002 Movement Disorder Society
Long‐term efficacy of botulinum toxin A in treatment of various movement disorders over a 10‐year period
Authors: Hsiung G‐Y.R. , Das S.K. , Ranawaya R. , Lafontaine A.‐L. , Suchowersky O.
Published: December 2002

Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long‐term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10‐year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty‐eight percent of patients discontinued treatment during the follow‐up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction. © 2002 Movement Disorder Society
Metric characteristics of the drug‐induced extrapyramidal symptoms scale (DIEPSS): A practical combined rating scale for drug‐induced movement disorders
Authors: Kim Jong‐Hoon , Jung Hee Yeon , Kang Ung Gu , Jeong Seong Hoon , Ahn Yong Min , Byun Hee‐Jung , Ha Kyoo‐Seob , Kim Yong Sik
Published: December 2002

The metric properties of the Drug‐Induced Extrapyramidal Symptoms Scale (DIEPSS) were examined in 182 subjects treated with antipsychotics. Inter‐rater reliability, test–retest reliability, and concurrent validity with other rating scales for EPS were high. Four factors were identified and the optimal diagnostic cut‐off scores were obtained. These results suggest that the DIEPSS is a reliable and valid multidimensional rating scale. © 2002 Movement Disorder Society
Levodopa but not ropinirole induces an internalization of D1 dopamine receptors in parkinsonian rats
Authors: Muriel Marie‐Paule , Orieux Gaël , Hirsch Etienne C.
Published: December 2002

Levodopa therapy in Parkinson's disease is mediated by dopamine receptors and, in a recent study, we showed that a Dl full agonist can induce an internalization of D1 dopamine receptors. The aim of the present study was to determine whether levodopa or a dopamine agonist such as ropinirole can also induce the internalization of D1 dopamine receptors in the striatum of control and hemiparkinsonian rats. The distribution of D1 dopamine receptors was analyzed by immunohistochemistry using a specific antibody. In control animals and 6‐hydroxydopamine (6‐OHDA)‐lesioned animals treated with saline, D1 dopamine receptors were localized at the level of the plasma membrane. In contrast, in both lesioned and nonlesioned animals receiving a single dose of levodopa, but not in animals receiving ropinirole, D1 dopamine receptors were internalized in the cytoplasm. This result is likely explained by the fact that ropinirole binds to non‐D1 dopamine receptors, whereas levodopa, which increases dopamine levels, indirectly acts on both D1 and D2 receptors. Ropinirole is consequently less likely to desensitize D1 dopamine receptors than levodopa and, thus, to reduce the efficacy of the treatment. © 2002 Movement Disorder Society
Large French‐Canadian family with Lewy body parkinsonism: Exclusion of known loci
Authors: Grimes David A. , Grimes J. David , Racacho Lem , Scoggan Kylie A. , Han Fabin , Schwarz Betty Anne , Woulfe John , Bulman Dennise
Published: December 2002

The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French‐Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two‐point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well‐documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of α‐synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The α‐synuclein(4q21.3‐23), Parkin(6q25.2‐27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase‐L1 (4p14‐16.3) and PARK6 and PARK7 (1p35‐36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome‐wide screen has been undertaken in an effort to identify a novel PD gene. © 2002 Movement Disorder Society
Apomorphine monotherapy in the treatment of refractory motor complications of Parkinson's disease: Long‐term follow‐up study of 64 patients
Authors: Manson Alice J. , Turner Kirsten , Lees Andrew J.
Published: December 2002

Continuous subcutaneous infusion of apomorphine is now increasingly recognized as an effective treatment for refractory off periods and peak‐dose dyskinesias in Parkinson's disease. We have reviewed our experience with apomorphine infusions, after a strategy decision in 1995 based on emerging preclinical data, to treat all patients with steady‐state plasma levels of apomorphine throughout the waking day, minimizing additional pulsatile stimulation either by oral dopaminergic medication or bolus parenteral injections of apomorphine. Sixty‐four patients have been treated with apomorphine pumps and 45 of these successfully converted to monotherapy, managing to discontinue all other forms of dopaminergic stimulation during the daytime treatment period with apomorphine. Patients were followed up for a mean of 33.8 months (range, 4–108 months) and clinical data analyzed retrospectively. The mean maintenance dose of apomorphine was 98 mg per 24 hours (monotherapy group: 103 mg/24 hours; polytherapy group: 93 mg/24 hours), which did not significantly increase at final follow‐up. There was a mean maximum dyskinesia reduction of 64% (S.D. = 20) in the monotherapy group, compared to 30% (S.D. = 33) in those continuing on polytherapy (P < 0.001), despite a maintained increase in on time (monotherapy group: 55%, P < 0.005; polytherapy group: 50%, P = 0.05). Fifteen patients failed to successfully convert to monotherapy but benefited nonetheless, and only 3 failed apomorphine infusional therapy altogether. Reasons for failure were mixed, including difficulty with compliance and adverse effects such as daytime somnolence, skin complications, and painful dystonias. There was a significantly higher success rate in patients able to manage the treatment either independently or with the help of their caregiver. These results confirm that subcutaneous apomorphine monotherapy can reset peak‐dose dyskinesia threshold in levodopa‐treated patients and further reduce off‐period disability after all available forms of oral medication, including long‐acting dopamine agonists, have been tried. © 2002 Movement Disorder Society
Dystonia: A disorder of motor programming or motor execution?
Authors: Kaňovský Petr
Published: December 2002

For some time, dystonia has been seen as purely a motor disorder. Relatively novel concepts published approximately 10 years ago also presumed that in the development of dystonic dyskinesias, only motor behaviour was abnormal. Neurophysiological observations of various types of dystonic disorders, which were performed using sophisticated electromyography, polymyography, H‐reflex examination, long‐latency reflex, etc., as well as new insights into the behaviour of dystonia, have urged the inclusion of sensory (particularly somatosensory) mechanisms into the pathophysiological background of dystonia. The major role has been considered to be played by abnormal proprioceptive input by means of the Ia proprioceptive afferents, with the source of this abnormality found in the abnormal processing of muscle spindle afferent information. However, neurophysiological investigations have also provided evidence that the abnormality in the central nervous system is located not only at the spinal and subcortical level, but also at the cortical level; specifically, the cortical excitability and intracortical inhibition have been revealed as abnormal. This evidence was revealed by SEP recordings, paired transcranial magnetic stimulation recordings, and BP and CNV recordings. The current concept of dystonic movement connects the abnormal function of somatosensory pathways and somatosensory analysers with the dystonic performance of motor action, which is based on the abnormality of sensorimotor integration. © 2002 Movement Disorder Society
Hemiballism after subthalamotomy in patients with Parkinson's disease: Report of 2 cases
Authors: Chen Chiung‐Chu , Lee Shih‐Tseng , Wu Tony , Chen Chi‐Jen , Huang Chin‐Chang , Lu Chin‐Song
Published: December 2002

The occurrence of persistent hemiballism after subthalamotomy for Parkinson's disease (PD) has not been described as frequently as mild or transient dyskinesia. We report on 2 patients with advanced PD who developed hemiballism and/or dyskinesia after subthalamotomy. One patient with a small lesion confined to the subthalamic nucleus (STN) developed persistent hemiballism; the other with a larger lesion involving the STN and also the zona incerta presented with a transient dyskinesia in a single limb. We conclude that a precise STN lesion might bear a potential risk of persistent hemiballism. © 2002 Movement Disorder Society
Neurophysiological investigations in patients with primary writing tremor
Authors: Modugno Nicola , Nakamura Yusaku , Bestmann Sven , Curra Antonio , Berardelli Alfredo , Rothwell John
Published: December 2002

The pathophysiology of primary writing tremor (PWT) is still unknown: it has been classified as a focal form of essential tremor and as a tremulous form of writer's cramp. We studied cortical and spinal excitability in patients with PWT and compared the results with published data of patients with essential tremor, and writer's cramp. We used electrical stimulation of median and radial nerve to study reciprocal inhibition of forearm antagonist muscles and paired transcranial magnetic stimulation at short and long interstimulus intervals (ISIs) to assess intracortical excitability. Both studies were conducted on patients with PWT and on control subjects. The early (presynaptic) and late (disynaptic) phases of reciprocal inhibition were normal as was intracortical excitability at short and long ISIs. Our study suggests that the pathophysiology of PWT is different from that of writer's cramp and partially also from that of essential tremor. © 2002 Movement Disorder Society
A broadband ADEQUATE pulse sequence using chirp pulses
Authors: Köck Matthias , Kerssebaum Rainer , Bermel Wolfgang
Published: December 2002

Recently, we have introduced the ADEQUATE pulse sequence as a sensitive method to observe 13C,13C correlations in natural products. This kind of experiment suffers from offset‐dependent effects of the 180°(13C) pulses. Here we describe an application of smoothed chirp pulses in the ADEQUATE pulse sequence which allows 13C,13C correlations to be run without any offset dependences. This experiment is called chirp ADEQUATE and was applied to δ‐valerolactone and cholesteryl acetate. This modification will allow a general application of the ADEQUATE pulse sequence. Copyright © 2002 John Wiley & Sons, Ltd.
Full multinuclear magnetic resonance analysis of 2,4‐dinitrofluorobenzene
Authors: Ariza‐Castolo Armando , Guerrero‐Alvarez Jorge Antonio , Peralta‐Cruz Javier
Published: December 2002

The complete assignment of the high‐resolution NMR spectra 2,4‐dinitrofluorobenzene was made, including the 1H, 13C, 15N, 17O and 19F nuclei. The 13C,19F, 13C,1H, 15N,19F and 15N,1H one‐bond and long‐range coupling constants were determinated and the signs were obtained by means of two‐dimensional correlation spectroscopy: 1H–1H‐COSY, 13C–1H‐COSY, 13C–1H‐COLOC and 1H–15N, 19F–15N and 19F–13C HMQC. The spin–lattice relaxation times of 13C revealed their anisotropy components and it was evident that the dipole–dipole contribution of fluorine was an efficient mechanism for C‐1 relaxation. The T1s of 1H agreed with the classical description: at low temperature the main contribution is dipole–dipole relaxation and at high temperature the relaxation is dominated by the spin–rotation mechanism. A linear relationship between δ13C(exp) and σC using GIAO (hybrid functional B3LYP) was found. 3J(13C, 1H) and the 1J(13C, 13C) have a relationship with the delocalization energies estimated by the NBO approach. Copyright © 2002 John Wiley & Sons, Ltd.
Brain metabolite composition during early human brain development as measured by quantitative in vivo 1H magnetic resonance spectroscopy
Authors: Kreis R. , Hofmann L. , Kuhlmann B. , Boesch C. , Bossi E. , Hüppi P.S.
Published: December 2002

Biochemical maturation of the brain can be studied noninvasively by 1H magnetic resonance spectroscopy (MRS) in human infants. Detailed time courses of cerebral tissue contents are known for the most abundant metabolites only, and whether or not premature birth affects biochemical maturation of the brain is disputed. Hence, the last trimester of gestation was observed in infants born prematurely, and their cerebral metabolite contents at birth and at expected term were compared with those of fullterm infants. Successful quantitative short‐TE 1H MRS was performed in three cerebral locations in 21 infants in 28 sessions (gestational age 32–43 weeks). The spectra were analyzed with linear combination model fitting, considerably extending the range of observable metabolites to include acetate, alanine, aspartate, cholines, creatines, γ‐aminobutyrate, glucose, glutamine, glutamate, glutathione, glycine, lactate, myo‐inositol, macromolecular contributions, N‐acetylaspartate, N‐acetylaspartylglutamate, o‐phosphoethanolamine, scyllo‐inositol, taurine, and threonine. Significant effects of age and location were found for many metabolites, including the previously observed neuronal maturation reflected by an increase in N‐acetylaspartate. Absolute brain metabolite content in premature infants at term was not considerably different from that in fullterm infants, indicating that prematurity did not affect biochemical brain maturation substantially in the studied population, which did not include infants of extremely low birthweight. Magn Reson Med 48:949–958, 2002. © 2002 Wiley‐Liss, Inc.
Water ADC, extracellular space volume, and tortuosity in the rat cortex after traumatic injury
Authors: Voříšek I. , Hájek M. , Tintěra J. , Nicolay K. , Syková E.
Published: December 2002

The diffusion parameters in rat cortex were studied 3–35 days following a cortical stab wound, using diffusion‐weighted MR to determine the apparent diffusion coefficient of water (ADCW) in the tissue, and the real‐time iontophoretic tetramethylammonium (TMA) method to measure the extracellular space (ECS) diffusion parameters: ECS volume fraction α and the ADC of TMA+ (ADCTMA). Severe astrogliosis was found close to the wound, and mild astrogliosis was found in the ipsilateral but not the contralateral cortex. Chondroitin sulfate proteoglycan (CSPG) expression was increased throughout the ipsilateral cortex. In the hemisphere contralateral to the wound, α, ADCTMA, and ADCW were not significantly different from control values. ECS volume fraction was increased only in the vicinity of the wound, in the region of cell death and severe astrogliosis, at 3 and 7 days after injury. However, both ADCTMA and ADCW were significantly decreased after lesion in the vicinity of the wound as well as in the rest of the ipsilateral hemisphere distant from the wound. Thus, both ADCW and ADCTMA decreased in regions wherein α did not change but CSPG increased. An increase in extracellular matrix expression may therefore impose diffusion barriers for water as well as for TMA molecules. Magn Reson Med 48:994–1003, 2002. © 2002 Wiley‐Liss, Inc.
Application of image registration to measurement of intervertebral rotation in the lumbar spine
Authors: Rogers Baxter P. , Haughton Victor M. , Arfanakis Konstantinos , Meyerand M. Elizabeth
Published: December 2002

In this study, the precision and accuracy of a new method for measuring axial rotations of the lumbar vertebrae, which are thought to be increased in patients with degenerative spinal instability, were estimated. A standard image registration algorithm involving a user‐selected center of rotation was adapted for this purpose. Accuracy was tested on a phantom containing a rotating lumbar vertebra. Calculated rotations were compared to the known values. Images were also obtained in subjects, using a tilting table that provided rotation between thorax and hips. For these measurements precision was estimated by varying the center of rotation. In the phantom the method had an accuracy of 0.2°. In the human subject measurements the precision was 0.60–1.5°. The method measured rotations of lumbar vertebrae with sufficient accuracy and precision to detect clinically significant differences in patients with back pain. Magn Reson Med 48:1072–1075, 2002. © 2002 Wiley‐Liss, Inc.
Remote control of catheter tip deflection: An opportunity for interventional MRI
Authors: Roberts T.P.L. , Hassenzahl W.V. , Hetts S.W. , Arenson R.L.
Published: December 2002

This study seeks to exploit the high magnetic field environment of a clinical MRI scanner and demonstrate the technical feasibility of developing a catheter whose tip can be remotely oriented within the magnetic field by applying a DC current to a coil wound around the catheter tip to generate a magnetic moment and consequent deflection. To achieve arbitrary three‐dimensional deflections, a three‐axis coil was wound on a 1.5 Fr cylindrical catheter. By applying DC currents in the 100 mA range, this catheter was successfully guided through a 3D phantom maze, mimicking the vasculature, under MR imaging guidance. Feasibility was demonstrated that the strong ambient magnetic field of the MR scanner offers a special opportunity to develop simple devices that can be remotely steered to sites of clinical interest. Magn Reson Med 48:1091–1095, 2002. © 2002 Wiley‐Liss, Inc.
Effects of raw garlic on physical performance and learning behaviour in rats
Authors: Sookvanichsilp Nongluck , Tiangda Chongkol , Yuennan Pirin
Published: December 2002

The effects of garlic (Allium sativum Linn.) on physical performance and learning behaviour were evaluated in male rats (7–8 months old, weighing 250–400 g) by comparison with the effects of pentoxifylline, a haemorheological agent with antiplatelet activity. The tests were designated as experiment A and experiment B, both conducted in two consecutive 4‐week sessions. In experiment A, the rats performed in a learning maze model during the first 4 weeks then followed by moving along the rope model for another 4 weeks. In experiment B, the rats were first tested in a rotarod treadmill for 4 weeks and then a step down test model for another 4 weeks. Each experiment consisted of four groups with 6–8 rats per group. Aqueous garlic homogenate at doses of 1 and 2 g (of raw garlic)/kg/day were given orally to group 1 and group 2, respectively, while pentoxifylline dispersion at a dose of 200 mg/kg/day was given to group 3. Group 4 served as the control group and was given water. All tests (maze model, rope model, rotarod model and step down model) were performed three times a week. The number of successful tasks and the acquisition time in 1 week intervals were used for the statistical analysis. The present results demonstrated that neither aqueous garlic homogenate at both doses nor pentoxifylline exhibited any benefit in the maze model or the rotarod model. Garlic only at the lower dose and pentoxifylline however, showed benefit in the rope model and step down model. These findings may provide some evidence to support the beneficial effect of long‐term garlic consumption on physical performance and learning behaviour in normal subjects. Copyright © 2002 John Wiley & Sons, Ltd.
Age and severity of nigrostriatal damage at onset of Parkinson's disease
Authors: de la Fuente‐Fernández Raúl , Lim Andrew S. , Sossi Vesna , Adam Michael J. , Ruth Thomas J. , Calne Donald B. , Stoessl A. Jon , Lee Chong S.
Published: December 2002

The clinical evolution of Parkinson's disease (PD) is known to be partly dependent on the age of onset. For example, motor complications associated with chronic dopaminomimetic treatment occur more often in younger patients. However, few attempts have been made to characterize the functional pathological differences underlying this age effect. We investigated the relationship between age and severity of nigrostriatal damage at onset of PD. Twenty patients with early PD (symptom duration ≤5 years) with onset before age 50 (n = 10) and with onset after age 50 (n = 10) were studied. The two groups were compared with respect to severity of nigrostriatal damage as evaluated by positron emission tomography (PET) scanning with 6‐[18F]fluoro‐L‐dopa ([18F]‐dopa), (±)‐α‐[11C]dihydrotetrabenazine ([11C]DTBZ), and d‐threo‐[11C]methylphenidate ([11C]MP). We found no significant differences between younger‐ and older‐onset PD patients with regard to any of the three presynaptic markers. For putamen, the P‐values corresponding to the different PET measurements ranged from P = 0.34 ([18F]‐dopa) to P = 0.79 ([11C]DTBZ). However, after adjusting for treatment and PD duration, regression analysis showed that [18F]‐dopa uptake correlated positively with age of onset (r = 0.59; P = 0.010). No correlation was found between [11C]DTBZ and [11C]MP binding potentials and age of onset (P = 0.26 and P = 0.90, respectively). These data suggest that age‐of‐onset‐dependent differences in clinical evolution are not likely to reflect early differences in nigrostriatal pathology in PD. Age‐related differences in [18F]‐dopa uptake may be related to changes in dopamine turnover. Synapse 47:152–158, 2003. © 2002 Wiley‐Liss, Inc.
The immunological synapse: the more you look the less you know…
Authors: Blanchard Nicolas , Hivroz Claire
Published: December 2002

Before T cells of the immune system can recognize pathogens, antigen presenting cells (APCs) must process pathogen‐derived peptides and present them together with major histocompatibility complex molecules (MHC) to T lymphocytes. T lymphocytes then scan the surface of APCs and antigen‐specific activation of the T cell will happen after interaction of T cell antigen receptor (TCR) with MHC—peptide complexes expressed at the membrane of APCs. This interaction takes place in a nanometer scale gap between the two cells, referred to as an immunological synapse. Recent three‐dimensional fluorescence analysis of this synapse revealed a dynamic spatial organization of membrane receptors, cytoskeleton and intracellular signaling complexes on the T cell side showing specific patterns, which depend on the nature of the T cell: APC pair. Although it is obvious that establishment of an intimate contact between T cells and APCs will facilitate cell:cell communication it is not clear what is the role, if any, of this receptors patterning. This molecular reorganization has long been thought to enhance and/or sustain TCR signaling and thus T cell activation, but this is now a matter of controversy. Moreover, mechanisms controlling immunological synapse formation are still unraveled. Segregation of proteins may occur spontaneously as proposed by mathematical modeling taking into account membrane fluidity, protein size and receptor/ligand affinity. Alternatively patterning of the molecules at the cell:cell interface could be driven by active processes involving T cell signaling and/or specific features of the APC. These different questions will be discussed herein.
Poly(A)‐binding protein and eRF3 are associated in vivo in human and Xenopus cells
Authors: Cosson Bertrand , Berkova Nadia , Couturier Anne , Chabelskaya Svetlana , Philippe Michel , Zhouravleva Galina
Published: December 2002

An interaction between human poly(A)‐binding protein (PABP) et human eRF3 has been demonstrated using a double‐hybrid approach and in vitro assays. Here, we show that the binding of both proteins is conserved through evolution. We also demonstrate that the last 39 C‐terminal amino acids of PABP contain the interface that interacts with eRF3. This region includes helix 5, identified by RMN, which is conserved in all known PABPs. Lastly, we demonstrate that eRF3 et PABP molecules interact in vivo.