bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene expression changes following androgen receptor elimination in LNCaP prostate cancer cells
Authors: Eder Iris E. , Haag Petra , Basik Mark , Mousses Spyro , Bektic Jasmin , Bartsch Georg , Klocker Helmut
Published: July 2003

We have shown recently that inhibition of androgen receptor (AR) expression with an antisense AR oligonucleotide (ODN) inhibits LNCaP prostate tumor cells in vitro as well as in vivo. In this study, we investigated gene expression changes that occur after AR signaling blockade, either through AR elimination by antisense treatment or through complete androgen receptor inhibition by androgen deprivation combined with the antiandrogen bicalutamide, in order to search for genes that are directly or indirectly regulated through the AR. Gene expression changes were investigated with cDNA NIH 10K gene microarrays in response to treatment over 48 h. Expression of selected genes was further analyzed by real‐time reverse transcriptase (RT)‐polymerase chain reaction (PCR), Western blotting, and radioimmunoassay. A comparison of antisense‐treated and androgen‐deprived cells revealed several concordances such as significant downregulation of prostate‐specific genes, cell‐cycle regulatory genes, genes of the cholesterol biosynthesis pathway, and several cytoskeletal genes. However, there were also several genes that were differentially regulated. Among the genes that were exclusively changed by treatment with the antisense AR ODN were the insulin‐like growth factor binding protein 2 (IGFBP2) and the phosphatidylinositol‐4‐phosphate 5‐kinase type I alpha (PIP5KIA). On the other hand, complete androgen receptor blockade induced changes in the expression of the prostate overexpressed gene 1 and the S100 calcium binding protein P. In summary, we identified a cohort of interesting genes whose expression was highly affected by elimination of the AR in LNCaP prostate cancer cells. Further investigations are warranted to clarify their role in the AR signaling pathway and their susceptibility as a target for the treatment of prostate cancer. © 2003 Wiley‐Liss, Inc.
Reduced gap junctional intercellular communication and altered biological effects in mouse osteoblast and rat liver oval cell lines transfected with dominant‐negative connexin 43
Authors: Upham Brad L. , Suzuki Junji , Chen Gang , Wang Yurong , McCabe Laura R. , Chang Chia‐Cheng , Krutovskikh Vladimir A. , Yamasaki Hiroshi , Trosko James E.
Published: July 2003

Gap junctional intercellular communication (GJIC) maintains normal growth and differentiation of cells in a tissue. The intercellular molecules traversing gap junctions are largely unknown, but the molecular weight (MW) cutoff is normally 1200 Da. No differences in dye transfer were observed in normal or vector controls of WB‐F344 rat liver epithelial or mouse osteoblastic MC3T3‐E1 cells with either Lucifer Yellow (LY) with a MW of 457 Da (LY‐457) or LY with a MW of 649 Da (LY‐649). Transfection of a dominant negative‐connexin 43 (Cx43) gene decreased GJIC (>50%) when LY‐649 was used, however, normal GJIC was observed in both cell lines when LY‐457 was used. Therefore, the MW cut off in these clones was considerably less than the wild type. The dominant negative clones of the MC3T3‐E1 cells exhibited over 90% less alkaline phosphatase (ALPase) activity and calcium deposition after the induction of differentiation. Similarly, dominant negative Cx43 inhibited gene expression of ALPase and bone sialoprotein but not osteocalcin in MC3T3‐E1. WB‐F344 cells normally exhibit a biphasic response to 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) where inhibition of GJIC recovers after 2 h, but the dominant negative clones showed no recovery from inhibition of GJIC by TPA. Dominant negative Cx43 also inhibited the formation of network‐like structures by WB‐F344 cells on Matrigel. These results demonstrate that the dominant negative gene transfected into cell types containing the wild‐type connexins result in diminished channel sizes, thus allowing the determination of whether distinct biological endpoints, i.e., differentiation, are dependent upon either small or high MW intercellular signals. © 2003 Wiley‐Liss, Inc.
Polymorphisms of estrogen receptor alpha in prostate cancer
Authors: Tanaka Yuichiro , Sasaki Masahiro , Kaneuchi Masanori , Shiina Hiroaki , Igawa Mikio , Dahiya Rajvir
Published: July 2003

Estrogen receptor (ER) α polymorphisms have been shown to be involved in the oncogenesis of several organs. We hypothesize that polymorphisms of the ERα gene are risk factors for prostate cancer. The genotypic distributions of six different loci (codons: 10 T → C, 87 G → C, 243 C → T, 325 C → G, 594 G → A, and intron 1 C → T) of the ERα gene were analyzed in prostate cancer tissues. The DNA from 115 cases of prostate cancer (Japanese population) was analyzed by sequence‐specific polymerase chain reaction (PCR) and direct sequencing to determine the genotypic and allelic frequencies of the six different polymorphic loci of ERα. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. Results of this study showed that the frequency of the variant genotype (C/C) on codon 10 was significantly higher in prostate cancer patients. The odds ratio (OR) was calculated as 3.26 compared to wild‐type (T/T) with a 95% confidence interval (CI) of 1.58–6.73. Allele frequency at codon 10 also differed between groups. No association was found between codon 10 polymorphism and the stage of cancer. Polymorphism was not observed in codon 87, and frequencies of genotypes and alleles at other loci (intron 1, codons 243, 325, and 594) were not statistically different between cancer and controls. The present study suggests that polymorphism in codon 10 of ERα may be a risk factor for prostate cancer. These results are important in understanding the role of ERα polymorphism in the pathogenesis of prostate cancer. © 2003 Wiley‐Liss, Inc.
Microarray analysis of xenograft‐derived cancer cell lines representing multiple experimental models of human prostate cancer
Authors: Glinsky Gennadi V. , Krones‐Herzig Anja , Glinskii Anna B. , Gebauer Gerhard
Published: July 2003

Expression analysis of 7129 transcripts was carried out in five human prostate cancer cell lines derived from orthotopic xenografts after one to five passages in nude mice and primary cultures of human normal prostate epithelial (NPE) cells. These experiments identified a consensus class of 214 genes (43 up‐ and 171 downregulated transcripts), expression of which was altered at least twofold in the same direction in all the cell lines relative to NPE cells. To validate the relevance of altered expression behavior of these genes for human prostate cancer, their expression pattern was evaluated in multiple additional experimental and clinical settings. Expression of 170 of these 214 genes (79%) was altered in the same direction in vivo in experimental human prostate tumors in mice. Similarly, the expression of 151 of the 214 genes (71%) was altered in the same direction in M12 cells, a variant of an SV40 large T antigen transformed normal human prostate epithelial cell line selected for increased malignancy in vivo. In clinical samples of human prostate tumors, the changes in transcript expression levels of majority of these genes (85% of downregulated and 76% of upregulated transcripts) are consistent with alterations of their expression pattern in xenograft‐derived cancer cell lines. These results imply that the expression pattern of a large class of genes is consistently altered in multiple experimental models and clinical samples of human prostate cancer and underscore the potential relevance of the xenograft models and cell lines derived from them for expression analysis studies relevant to human cancer. © 2003 Wiley‐Liss, Inc.
Lower risk of Parkinson's disease in an admixed population of European and Indian origins
Authors: Ragothaman Mona , Murgod Uday A. , Gururaj Gopalkrishna , Kumaraswamy Subbakrishna D. , Muthane Uday
Published: July 2003

We studied whether the occurrence of Parkinson's disease (PD) in the Anglo‐Indians, an admixed population of European and Asian Indian origin, differs from Indians living in the same environment. Epidemiological studies show considerably higher prevalence of PD amongst white compared to non‐white populations. Normal Indians contain a ∼40% lower number of melanized nigral neurons compared to Caucasians from the UK. Anglo‐Indians are an admixed population of European and Indian origin. We used the UK Parkinson's Disease Society Brain Bank clinical diagnostic criteria (steps 1 and 2) to diagnose PD in 84 of 493 residents (Indians, 409; Anglo‐Indians, 84) living in elderly homes in Bangalore, India. Of these 84, 80 were Indians (19.5%) and 4 were Anglo‐Indians (4.8%). Occurrence of PD is nearly five times higher amongst Indians compared to the Anglo‐Indians (odds ratio, 3.9; 95% confidence interval, 1.3–12.9). We conclude that an admixture population of European and Indian origins, rather than averaging, might result in reduced occurrences of PD. Hence, studying an admixed population could provide crucial insights into understanding genetic mechanisms in the etiopathogenesis of PD. © 2003 Movement Disorder Society
Head retraction reflex in stiff‐man syndrome and related disorders
Authors: Berger Christian , Meinck Hans‐Michael
Published: July 2003

The head retraction reflex (HRR) is a vestigial withdrawal reflex of the face and is suppressed in healthy subjects. We investigated the prevalence and electrophysiological patterns of the HRR in patients suffering from stiff‐man syndrome (SMS, n = 28) and related disorders, stiff‐limb syndrome (SLS, n = 2), and progressive encephalomyelitis with rigidity and myoclonus (PERM, n = 20). In patients with a positive HRR, the electromyographic (EMG) pattern was analyzed with surface recordings from the orbicularis oculi, sternocleidomastoid, trapezius, and the paraspinal extensor muscles at midthoracic and lumbar levels. On clinical testing, 17 of 28 SMS patients, 10 of 20 PERM patients, and 0 of 2 SLS patients had a positive HRR, ranging from a brief contraction of the neck extensors to violent retropulsion of the upper body. In all muscles, EMG reflex patterns elicited by gentle taps to the face or by electrical stimulation of the trigeminal nerve branches consisted of two components: an early, synchronous, brief burst with the shortest latency in trapezius (12.5–20.0 msec) and a late, asynchronous, longer response with latencies between 44 and 70 msec. We conclude that the HRR is an abnormal cutaneomuscular brainstem reflex that occurs in a considerable proportion of patients with SMS and related disorders. Although neither specific nor particularly sensitive for SMS, presence of the HRR in a setting with otherwise unexplained stiffness and spasms might help to avoid the otherwise frequent misdiagnosis of a psychogenic motor disturbance in patients with SMS. © 2003 Movement Disorder Society
Altered corticomotor representation in patients with Parkinson's disease
Authors: Kagerer Florian A. , Summers Jeff J. , Byblow Winston D. , Taylor Bruce
Published: July 2003

In 6 patients with Parkinson's disease (PD) and 6 age‐matched controls, transcranial magnetic stimulation was applied at 56 regions over the motor cortex and premotor cortex of each hemisphere, with the first dorsal interosseous (FDI) muscle of both hands activated at 15% maximum voluntary contraction during stimulation. For each site, motor evoked potential (MEP) landmarks were recovered, including MEP amplitude, MEP onset latency, and silent period duration. Scaled MEP amplitudes were used to construct individual cortical maps of the FDI muscles. The maps revealed an anterior displacement of the muscle representation in PD patients. This anterior shift over motor cortical areas may reflect increased contributions of corticocortical connections between motor cortex and premotor cortical areas, possibly enhanced by the visual feedback aspect of the task. These alterations may reflect adaptations to the impairments in striatocortical circuits in PD. © 2003 Movement Disorder Society
Unique form of propriospinal myoclonus as a possible complication of an enteropathogenic toxin
Authors: Espay Alberto J. , Ashby Peter , Hanajima Ritsuko , Jog Mandar S. , Lang Anthony E.
Published: July 2003

Propriospinal myoclonus is an uncommon form of spinal myoclonus propagated, presumably, by slowly conducting polysynaptic intraspinal pathways. Although most patients demonstrate no clear etiology, a variety of disorders have been linked to this abnormal movement, including trauma, multiple sclerosis, tumors, and infectious disorders such as herpes zoster, human immunodeficiency virus, and Lyme disease. We describe 2 young male patients from the same town in Northern Ontario, Canada, exposed to an outbreak of Escherichia coli O157:H7 from contaminated municipal water, who developed identical clinical and electrophysiological features suggestive of a rhythmic form of propriospinal myoclonus with activity alternating between abdominal and paraspinal muscles. A toxin‐mediated microvascular thrombosis is proposed as a possible pathogenic mechanism underlying this novel association. © 2003 Movement Disorder Society
Multiple sclerosis tremor and the Stewart‐Holmes manoeuvre
Authors: Waubant Emmanuelle , Tezenas du Montcel Sophie , Jedynak Charles , Obadia Michael , Hosseini Hassan , Damier Philippe , Lubetzki Catherine , Agid Yves , Degos Jean‐Denis
Published: July 2003

The objective of this study is to define tremor and cerebellar dysfunction and determine whether kinetic and postural tremor correlate with cerebellar dysfunction in patients with multiple sclerosis (MS). Cerebellar symptoms such as dysmetria often interfere with tremor evaluation in MS. The Stewart‐Holmes (SH) manoeuvre, which has been recently quantified, may offer a selective evaluation of cerebellar dysfunction in such patients. Thirty‐two patients with definite MS and arm tremor were evaluated (simplified Fahn tremor scale for kinetic and postural tremor, finger‐to‐nose test, clinical SH manoeuvre, quantitative study of the SH manoeuvre). Median severity of kinetic and postural tremor on the most disabled side was, respectively, 2 (range 0–4) and 1.5 (range 0–4). Clinical SH scores were moderately correlated to quantified SH measures (r = 0.36, P < 0.05). Kinetic and postural tremors were strongly correlated (r = 0.73, P < 0.0001) but did not correlate with clinical or quantified SH scores. Patients with bilateral tremor had higher scores for quantified SH, and a trend to higher clinical SH and finger‐to‐nose scores than patients with unilateral tremor. Although clinically associated, cerebellar dysfunction and tremor may be partly independent symptoms, suggesting they may relate to dysfunction of different neuronal systems. The SH manoeuvre should be part of the evaluation of MS patients considered for surgery of tremor. © 2003 Movement Disorder Society
Extrapyramidal features in Parkinson's disease with and without dementia and dementia with Lewy bodies: A cross‐sectional comparative study
Authors: Burn David J. , Rowan Elise N. , Minett Thais , Sanders Jonathon , Myint Pat , Richardson Jonathon , Thomas Alan , Newby Jane , Reid Jenny , O'Brien John T. , McKeith Ian G.
Published: July 2003

Risk factors predicting an increased risk of dementia in Parkinson's disease (PD) are not fully established. The dementia associated with PD (PDD) closely resembles dementia with Lewy bodies (DLB). Based upon a high frequency of non‐dopaminergic mediated clinical features in DLB, we predicted that a motor subtype comprising postural instability and balance problems would be more common in PDD. We examined extrapyramidal, cognitive, and affective features in 38 PD, 43 PDD, and 26 DLB patients in a cross‐sectional study design. Motor subtype was subdivided into postural‐instability gait difficulty (PIGD) or tremor (TD) dominant. The PIGD‐subtype was more common in PDD (88% of cases) and DLB (69% of cases) groups compared with the PD group (38% of cases), in which TD and PIGD sub‐types were more equally represented (P < 0.001). Although the mean depression scores overall were modest, PDD patients scored significantly higher than PD, but not DLB patients (Cornell; P = 0.006, and Geriatric Depression scale, GDS‐15; P = 0.001), while within the PD group, those patients with a PIGD subtype had greater depression scores than the TD subtype (GDS‐15; P < 0.05). We conclude that non‐dopaminergic motor features are frequent in PDD. Neurodegeneration within the cholinergic system is likely to mediate many of these motor problems, as well as playing a significant role in determining the neuropsychiatric symptomatology of both PDD and DLB. © 2003 Movement Disorder Society
Life‐threatening respiratory failure due to cranial dystonia after dental procedure in a patient with multiple system atrophy
Authors: Hamzei Farsin , Rijntjes Michel , Gbadamosi Joystone , Fuchs Kornelius , Weiller Cornelius , Münchau Alexander
Published: July 2003

We report on a woman with a an 8‐year history of multiple system atrophy with predominance of parkinsonism who developed jaw‐locking oromandibular dystonia within hours after insertion of ill‐fitting dentures. Dystonia spread rapidly to involve other facial muscles and the larynx causing stridor with respiratory failure necessitating crush intubation. © 2003 Movement Disorder Society
Staged lesions through implanted deep brain stimulating electrodes: A new surgical procedure for treating tremor or dyskinesias
Authors: Raoul Sylvie , Faighel Mirella , Rivier Isabelle , Vérin Marc , Lajat Youenn , Damier Philippe
Published: July 2003

Thalamotomy and pallidotomy have been shown to have some efficacy for treating some movement disorders such as disabling tremor or parkinsonian levodopa‐induced dyskinesias (LID). Compared to continuous deep brain stimulation (DBS), this surgical procedure has the disadvantage of irreversibility and a lack of adaptability. Making a lesion involves a risk of inducing permanent side effects, especially if the lesion is large, or of observing a resurgence of the symptoms if the lesion is too small. We performed unilateral pallidotomy in one patient suffering from LID and unilateral thalamotomy in two patients suffering from tremor through the lead classically used for DBS. The technique of lead implantation was similar to that used for DBS treatment but, instead of connecting the lead to a pulse generator, it was left in place and used to make a radiofrequency lesion. This technique allowed the lesion to be kept as small as possible, thereby minimizing the risk of permanent side effects and made possible to extend the lesion if the symptoms reappeared. One lesioning session was enough to relieve tremor in the two patients treated by thalamotomy; three lesioning sessions over a 7‐month period were required to relieve drug‐induced dyskinesias in the patient treated by pallidotomy. In all 3 patients, disabling symptoms were still relieved without any permanent side effects 6 months after the last lesion was performed. © 2003 Movement Disorder Society
Cardiac MIBG scintigraphy is a sensitive tool for detecting cardiac sympathetic denervation in Parkinson's disease
Authors: Courbon Frédéric , Brefel‐Courbon Christine , Thalamas Claire , Alibelli Marie Jeanne , Berry Isabelle , Montastruc Jean‐Louis , Rascol Olivier , Senard Jean‐Michel
Published: July 2003

[123I]Metaiodobenzylguanidine ([123I]MIBG) cardiac scintigraphy could be helpful to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), demonstrating that, in PD with autonomic failure but not in MSA, there is a myocardial postganglionic sympathetic dysfunction. To investigate whether this method is more sensitive than standard autonomic testing to detect early involvement of sympathetic cardiac efferent, we analyse MIBG myocardial uptake in 8 PD patients with normal autonomic testing (nondysautonomia PD group, NDPD) in comparison with 10 PD patients with abnormal autonomic testing (dysautonomia PD group, DPD) and 10 MSA patients. Global MIBG uptake was assessed using the ratio of [123I]MIBG uptake in the heart to the upper mediastinum (H/M) on planar scintigraphic data. Regional MIBG uptake was determined on two single photon emission tomography scans in regions of the left ventricle. The mean H/M ratios were significantly different among the three groups (P < 0.0001). H/M ratios of both NDPD and DPD patients groups (H/M = 1.83 ± 0.50 and 1.24 ± 0.40, respectively) were significantly lower than in MSA patients (H/M = 2.52 ± 0.60). However, in NDPD patients, H/M was significantly higher than in DPD patients. When compared to MSA patients, NDPD patients showed a regional reduction in MIBG uptake in all left ventricle regions markedly in the apex and the inferior wall. Our results suggest that MIBG myocardial scintigraphy (analysis of both H/M ratio and regional MIBG uptake) may be more sensitive than standard autonomic testing for the early detection of silent autonomic dysfunction in PD. © 2003 Movement Disorder Society
Influence of monocyte chemoattractant protein 1 gene polymorphism on age at onset of sporadic Parkinson's disease
Authors: Nishimura Masataka , Kuno Sadako , Mizuta Ikuko , Ohta Mitsuhiro , Maruyama Hirofumi , Kaji Ryuji , Kawakami Hideshi
Published: July 2003

We studied polymorphisms in the genes for monocyte chemoattractant protein 1 (MCP‐1) and CC chemokine receptor (CCR)‐2 in 171 Parkinson's disease (PD) patients and 340 controls. Although no associations were found in alleles or genotypes, MCP‐1 −2518A/G genotype affected the age‐at‐onset of PD patients. This effect was also detected in a second PD group, suggesting a possible involvement of MCP‐1 in PD. © 2003 Movement Disorder Society
Transplantation in Parkinson's disease: PET changes correlate with the amount of grafted tissue
Authors: Cochen Valérie , Ribeiro Maria‐Joao , Nguyen Jean‐Paul , Gurruchaga Jean‐Marc , Villafane Gabriel , Loc'h Christian , Defer Gilles , Samson Yves , Peschanski Marc , Hantraye Philippe , Cesaro Pierre , Remy Philippe
Published: July 2003

An erratum for this article appears in the January, 2004 issue of Movement Disorders (Mov Disord 2004;12:119).

We compared the striatal uptake of [18F]fluorodopa with [76Br]‐FE‐CBT, a positron emission tomography (PET) ligand of the dopamine transporter (DAT), which estimates the density of dopamine nerve terminals, in 6 patients with Parkinson's disease grafted with fetal mesencephalic cells. There was no change in DAT ligand binding in the grafted putamen, despite a significant increase of [18F]fluorodopa uptake. This finding suggests that the clinical benefit induced by the graft is more related to increased dopaminergic activity than improved dopaminergic innervation in the host striatum and, therefore, that [18F]fluorodopa remains the optimal tracer to evaluate grafted PD patients. Further analysis showed that the clinical and [18F]fluorodopa uptake changes after the grafts were correlated with the number of ventral mesencephalae used for implantation. © 2003 Movement Disorder Society
Fipamezole (JP‐1730) is a potent α2 adrenergic receptor antagonist that reduces levodopa‐induced dyskinesia in the MPTP‐lesioned primate model of Parkinson's disease
Authors: Savola Juha‐Matti , Hill Michael , Engstrom Mia , Merivuori Hannele , Wurster Siegfried , McGuire Steven G. , Fox Susan H. , Crossman Alan R. , Brotchie Jonathan M.
Published: July 2003

Previous studies in the MPTP‐lesioned primate model of Parkinson's disease have demonstrated that α2 adrenergic receptor antagonists such as idazoxan, rauwolscine, and yohimbine can alleviate L‐dopa–induced dyskinesia and, in the case of idazoxan, enhance the duration of anti‐parkinsonian action of L‐dopa. Here we describe a novel α2 antagonist, fipamezole (JP‐1730), which has high affinity at human α2A (Ki, 9.2 nM), α2B (17 nM), and α2C (55 nM) receptors. In functional assays, the potent antagonist properties of JP‐1730 were demonstrated by its ability to reduce adrenaline‐induced 35S‐GTPγS binding with KB values of 8.4 nM, 16 nM, 4.7 nM at human α2A, α2B, and α2C receptors, respectively. Assessment of the ability of JP‐1730 to bind to a range of 30 other binding sites showed that JP‐1730 also had moderate affinity at histamine H1 and H3 receptors and the serotonin (5‐HT) transporter (IC50 100 nM to 1 μM). In the MPTP‐lesioned marmoset, JP‐1730 (10 mg/kg) significantly reduced L‐dopa–induced dyskinesia without compromising the anti‐parkinsonian action of L‐dopa. The duration of action of the combination of L‐dopa and JP‐1730 (10 mg/kg) was 66% greater than that of L‐dopa alone. These data suggest that JP‐1730 is a potent α2 adrenergic receptor antagonist with potential as an anti‐dyskinetic agent in the treatment of Parkinson's disease. © 2003 Movement Disorder Society
Cabergoline versus levodopa monotherapy: A decision analysis
Authors: Smala Antje M. , Spottke E. Annika , Machat Olaf , Siebert Uwe , Meyer Dieter , Köhne‐Volland Rudolf , Reuther Martin , DuChane Janeen , Oertel Wolfgang H. , Berger Karin B. , Dodel Richard C.
Published: July 2003

We evaluated the incremental cost‐effectiveness of cabergoline compared with levodopa monotherapy in patients with early Parkinson's disease (PD) in the German healthcare system. The study design was based on cost‐effectiveness analysis using a Markov model with a 10‐year time horizon. Model input data was based on a clinical trial “Early Treatment of PD with Cabergoline” as well as on cost data of a German hospital/office‐based PD network. Direct and indirect medical and nonmedical costs were included. Outcomes were costs, disease stage, cumulative complication incidence, and mortality. An annual discount rate of 5% was applied and the societal perspective was chosen. The target population included patients in Hoehn and Yahr Stages I to III. It was found that the occurrence of motor complications was significantly lower in patients on cabergoline monotherapy. For patients aged ≥60 years of age, cabergoline monotherapy was cost effective when considering costs per decreased UPDRS score. Each point decrease in the UPDRS (I‐IV) resulted in costs of €1,031. Incremental costs per additional motor complication‐free patient were €104,400 for patients <60 years of age and €57,900 for patients ≥60 years of age. In conclusion, this decision‐analytic model calculation for PD was based almost entirely on clinical and observed data with a limited number of assumptions. Although costs were higher in patients on cabergoline, the corresponding cost‐effectiveness ratio for cabergoline was at least as favourable as the ratios for many commonly accepted therapies. © 20032003 Movement Disorder Society
Olfactory bulb in multiple system atrophy
Authors: Kovács Tibor , Papp Mátyás I. , Cairns Nigel J. , Khan M. Nadeem , Lantos Peter L.
Published: July 2003

Olfactory dysfunction is a characteristic clinical sign in Parkinson's disease (PD); it is also present in multiple system atrophy (MSA). The pathological basis of hyposmia or anosmia in PD is well known: the olfactory bulb (OB) contains numerous Lewy bodies and severe neuronal loss is present in the anterior olfactory nucleus (AON). We established that glial cytoplasmic inclusions (GCIs) are present in all the OBs from MSA cases. Their presence in the OB is diagnostic for MSA. Additionally, neuronal loss is present in the AON in MSA. These pathological changes might be responsible for the olfactory dysfunction seen in MSA. © 2003 Movement Disorder Society
Mutation analysis of the parkin gene in Russian families with autosomal recessive juvenile parkinsonism
Authors: Illarioshkin Sergei N. , Periquet Magali , Rawal Nina , Lücking Christoph B. , Zagorovskaya Tatyana B. , Slominsky Pyotr A. , Miloserdova Olga V. , Markova Elena D. , Limborska Svetlana A. , Ivanova‐Smolenskaya Irina A. , Brice Alexis
Published: July 2003

Autosomal recessive juvenile parkinsonism (AR‐JP) is a form of hereditary parkinsonism characterized by variable clinical presentations and caused by mutations in a novel gene, parkin, on chromosome 6q25.2–27. Until now, no Russian cases of parkin‐associated AR‐JP have been reported on. We recruited 16 patients from 11 Russian families with dopa‐responsive movement disorders according to the following criteria: 1) family history compatible with autosomal recessive inheritance; 2) onset of symptoms at ≤30 years of age; and 3) the lack of mutations in the GTP cyclohydrolase I gene (in sporadic cases). Mutation screening of the parkin gene was carried out by a semiquantitative PCR assay and direct sequencing of the coding region. Six different parkin mutations (both deletions and point mutations) were identified in the index cases from four families, including a novel point mutation in the donor splice site (IVS1+1G→A). The majority of our parkin‐associated cases were characterized by early‐onset dopa‐responsive parkinsonism with benign course and slow progression (5 patients from two families have been followed for as long as 18–36 years), and 1 patient had a phenotype of dopa‐responsive dystonia. This first description of Russian patients with AR‐JP and molecularly proven parkin mutations confirms the widespread occurrence of this polymorphic hereditary extrapyramidal disorder. © 2003 Movement Disorder Society
Delineating the sites and progression of in vivo atrophy in multiple system atrophy using fluid‐registered MRI
Authors: Schott Jonathan M. , Simon Jessica E. , Fox Nick C. , King Andrew P. , Khan M. Nadeem , Cipolotti Lisa , Paviour Dominic C. , Stevens John M. , Rossor Martin N.
Published: July 2003

We describe the pattern and progression of atrophy delineated using fluid registration of serial magnetic resonance imaging scans in a case of multiple system atrophy (MSA). The in vivo findings were consistent with those found at postmortem, including significant supratentorial atrophy concurrent with an unusual degree of cognitive impairment for MSA. © 2003 Movement Disorder Society
Myoclonus in spinal dysraphism
Authors: Warren Jane E. , Vidailhet Marie , Kneebone Christopher S. , Quinn Niall P. , Thompson Philip D.
Published: July 2003

Two cases of segmental myoclonus occurring in association with spinal dysraphism are described. In one, myoclonus of paralysed legs arose below a region of spinal cord lacking any normal function, illustrating the capacity of the isolated spinal cord to generate and maintain rhythmic activity independent of supraspinal influences. © 2003 Movement Disorder Society
From functional neurosurgery to “interventional” neurology: Survey of publications on thalamotomy, pallidotomy, and deep brain stimulation for Parkinson's disease from 1966 to 2001
Authors: Hariz Marwan I.
Published: July 2003

Articles on surgery for Parkinson's disease (PD), published between 1966 and 2001, were reviewed with respect to whether the first author had a neurosurgical affiliation, and whether the papers appeared in neurosurgical or non‐neurosurgical journals. Between 1966 and 1979, neurosurgeons and non‐neurosurgeons published almost equally on surgery for PD in both neurosurgical and non‐neurosurgical journals; between 1980 and 1995, the majority of publications were by neurosurgeons in neurosurgical journals; and after 1995, non‐neurosurgeons were more often first authors of surgical publications and these were more frequent in non‐neurosurgical journals. The fact that the first author of surgical publications on PD is often a non‐neurosurgeon may have some bearing on the reported results of surgery. © 2003 Movement Disorder Society
Spatial learning in rats is impaired after degeneration of the nigrostriatal dopaminergic system
Authors: Mura Anna , Feldon Joram
Published: July 2003

We investigated spatial learning in rats with unilateral and bilateral lesions of the nigrostriatal dopaminergic system. We used the Morris water maze paradigm, which tests spatial forms of learning and memory and allows discrimination between sensory‐motor and learning disabilities. Animals were trained preoperatively to learn the location of a spatially fixed hidden platform to escape from the swimming pool (acquisition training). A visual and a probe test were used before and after the acquisition training, respectively. Our results show that animals with unilateral lesions, although displaying longer escape latencies, have normal spatial memory abilities. Animals with bilateral lesions were able to swim as fast or even faster than animals with unilateral lesion. Despite the fact that these animals had learned the spatial navigation tasks preoperatively, bilateral dopaminergic lesions led to a profound deficit in ability to find a hidden platform during an acquisition task. In general, animals with bilateral lesions persisted in swimming along the pool walls and their spatial navigation performance during a probe test was very poor. These results suggest that deficit of the nigrostriatal dopaminergic system can affect the selection and maintenance of behavioral strategies in spatial navigation. © 2003 Movement Disorder Society
Network optimization in supply chain management and financial engineering: An annotated bibliography
Authors: Geunes Joseph , Pardalos Panos M.
Published: July 2003

During the past decade, two relatively new application areas have attracted the attention of a growing number of researchers who specialize in applying optimization techniques to large‐scale real‐world problems. The now well‐known areas of supply chain management and financial engineering have provided extremely rich contexts for the definition of new large‐scale optimization problems, the solutions of which can provide substantial value to organizations. This paper discusses the extent to which network optimization approaches have contributed to the advancement of supply chain management and financial engineering research through an examination of past literature involving network optimization applications within these still emerging fields. © 2003 Wiley Periodicals, Inc.
Cycle embedding in faulty wrapped butterfly graphs
Authors: Tsai Chang‐Hsiung , Liang Tyne , Hsu Lih‐Hsing , Lin Men‐Yang
Published: July 2003

In this paper, we study the maximal length of cycle embedding in a faulty wrapped butterfly graph BFn with at most two faults in vertices and/or edges. When there is one vertex fault and one edge fault, we prove that the maximum cycle length is n2n − 2 if n is even and n2n − 1 if n is odd. When there are two faulty vertices, the maximum cycle length is n2n − 2 for odd n. All these results are optimal because the wrapped butterfly graph is bipartite if and only if n is even. © 2003 Wiley Periodicals, Inc.
The performance of QoS‐aware IP multicast routing protocols
Authors: Tseng Chih‐Jen , Chen Chyou‐Hwa
Published: July 2003

Research in the area of QoS‐aware dynamic multicast routing protocols has been very active in recent years. Protocols based on dynamic Steiner tree strategies, such as YAM and QoSMIC, have been consistently shown to outperform those based on shortest path heuristics, such as PIM and DVMRP. However, these protocols all suffer from the problem of poor scalability for one or more of the following reasons: high control overhead, insufficient robustness with the adoption of a centralized group manager, and excessively long join latency. In addition, these protocols perform well only when group members are either densely populated or sparsely populated, but, unfortunately, not both. In this paper, we propose a protocol, named DSDMR, which can adapt its strategy based on sensed group member densities. Underlying DSDMR is an adaptive two‐direction join mechanism that tries to find good attaching points for new group members either from the source or from the new joining member depending on member densities. We evaluate our scheme using extensive simulations and found that DSDMR can build multicast trees with costs close to the best greedy strategy, very low control overhead, and very short join latency across a wide member density spectrum. Furthermore, its success ratio is only slightly lower than is the best greedy strategy in finding feasible routes subject to both bandwidth and end‐to‐end delay constraints. © 2003 Wiley Periodicals, Inc.
Some recent contributions to routing and location problems
Authors: Corberán A. , Mota E. , Salazar J. J.
Published: July 2003

This report is more than just a summary of some results of the present state of the art in routing and location problems. It summarizes theoretical insights, modeling approaches, and heuristic and exact algorithms for routing and location presented at the CORAL 2003 Workshop held in Tenerife (Spain). © 2003 Wiley Periodicals, Inc.
An annotated bibliography of network interior point methods
Authors: Resende Mauricio G. C. , Veiga Geraldo
Published: July 2003

This paper presents an annotated bibliography on interior point methods for solving network flow problems. We consider single and multi‐commodity network flow problems, as well as preconditioners used in implementations of conjugate gradient methods for solving the normal systems of equations that arise in interior point network flow algorithms. Applications in electrical engineering and miscellaneous papers complete the bibliography. The collection includes papers published in journals and books, Ph.D. dissertations, and unpublished technical reports. © 2003 Wiley Periodicals, Inc.
Analysis of microstructure development in shearbands by energy relaxation of incremental stress potentials: Large‐strain theory for standard dissipative solids
Authors: Miehe Christian , Lambrecht Matthias
Published: July 2003

We propose a fundamentally new approach to the treatment of shearband localizations in strain softening elastic–plastic solids at finite strains based on energy minimization principles associated with microstructure developments. The point of departure is a general internal variable formulation that determines the finite inelastic response as a standard dissipative medium. Consistent with this type of inelasticity we consider an incremental variational formulation of the local constitutive response where a quasi‐hyperelastic stress potential is obtained from a local constitutive minimization problem with respect to the internal variables. The existence of this variational formulation allows the definition of the material stability of an inelastic solid based on weak convexity conditions of the incremental stress potential in analogy to treatments of finite elasticity. Furthermore, localization phenomena are interpreted as microstructure developments on multiple scales associated with non‐convex incremental stress potentials in analogy to elastic phase decomposition problems. These microstructures can be resolved by the relaxation of non‐convex energy functionals based on a convexification of the stress potential. The relaxed problem provides a well‐posed formulation for a mesh‐objective analysis of localizations as close as possible to the non‐convex original problem. Based on an approximated rank‐one convexification of the incremental stress potential we develop a computational two‐scale procedure for a mesh‐objective treatment of localization problems at finite strains. It constitutes a local minimization problem for a relaxed incremental stress potential with just one scalar variable representing the intensity of the microshearing of a rank‐one laminate aligned to the shear band. This problem is sufficiently robust with regard to applications to large‐scale inhomogeneous deformation processes of elastic–plastic solids. The performance of the proposed energy relaxation method is demonstrated for a representative set of numerical simulations of straight and curved shear bands which report on the mesh independence of the results. Copyright © 2003 John Wiley & Sons, Ltd.
Boundary element analysis of curved cracked panels with adhesively bonded patches
Authors: Wen P. H. , Aliabadi M. H. , Young A.
Published: July 2003

A new boundary element formulation for analysis of curved cracked panels with adhesively bonded patches is presented in this paper. The effect of the adhesive layer is modelled by distributed body forces (i.e. two in‐plane forces, two moments and one out‐of‐plane force). A coupled boundary integral formulation of a shear deformable plate and two‐dimensional plane stress elasticity is used to determine bending and membrane forces along the adhesive layer taking into consideration the compatibility conditions in the patch area. Two numerical examples are presented to demonstrate the efficiency of the proposed method. It is shown that the out‐of‐plane bending behaviour and panel curvature have significant influence on the magnitude of the stress intensity factors. Copyright © 2003 John Wiley & Sons, Ltd.
A fictitious domain decomposition method for the solution of partially axisymmetric acoustic scattering problems. Part 2: Neumann boundary conditions
Authors: Hetmaniuk U. , Farhat C.
Published: July 2003

We present a fictitious domain decomposition method for the fast solution of acoustic scattering problems characterized by a partially axisymmetric sound‐hard scatterer. We apply this method to the solution of a mock‐up submarine problem, and highlight its computational advantages and intrinsic parallelism. A key component of our method is an original idea for addressing a Neumann boundary condition in the general framework of a fictitious domain method. This idea is applicable to many other linear partial differential equations besides the Helmholtz equation. Copyright © 2003 John Wiley & Sons, Ltd.
Layout optimization with h‐adaptivity of structures
Authors: Costa Jr João Carlos Arantes , Alves Marcelo Krajnc
Published: July 2003

In this paper, we propose a new procedure for the layout optimization of structures making use of h‐adaptive methods. The method combines the topology optimization and the existing h‐adaptive finite element methods in order to: (i) improve the definition of the material boundary, i.e. the contour between the material and void regions; (ii) reduce the effective number of design variables; and (iii) bound the relative solution error. The refinement strategy is applied to a given element if: (a) the measure of the quality of the element is below a given lower bound; (b) the element is a ‘material element’ or has a side which forms the ‘material boundary’ of the given optimum layout; and (c) the element average error estimate is larger than a multiple of the average error of the mesh. After the h‐adaptive refinement, the mesh quality is improved with the application of a conditional Laplacian smoothing process. The formulation of the optimization problem is defined by the minimization of the compliance of the structure subjected to a volume and side constraints. The design variable is then the average density of the material, which is considered to be constant within each finite element. Copyright © 2003 John Wiley & Sons, Ltd.
A meshfree method for incompressible fluid dynamics problems
Authors: Tsukanov I. , Shapiro V. , Zhang S.
Published: July 2003

We show that meshfree variational methods may be used for the solution of incompressible fluid dynamics problems using the R‐function method (RFM). The proposed approach constructs an approximate solution that satisfies all prescribed boundary conditions exactly using approximate distance fields for portions of the boundary, transfinite interpolation, and computations on a non‐conforming spatial grid. We give detailed implementation of the method for two common formulations of the incompressible fluid dynamics problem: first using scalar stream function formulation and then using vector formulation of the Navier–Stokes problem with artificial compressibility approach. Extensive numerical comparisons with commercial solvers and experimental data for the benchmark back‐facing step channel problem reveal strengths and weaknesses of the proposed meshfree method. Copyright © 2003 John Wiley & Sons, Ltd.
Extended finite element method for quasi‐brittle fracture
Authors: Mariani Stefano , Perego Umberto
Published: July 2003

A methodology for the simulation of quasi‐static cohesive crack propagation in quasi‐brittle materials is presented. In the framework of the recently proposed extended finite element method, the partition of unity property of nodal shape functions has been exploited to introduce a higher‐order displacement discontinuity in a standard finite element model. In this way, a cubic displacement discontinuity, able to reproduce the typical cusp‐like shape of the process zone at the tip of a cohesive crack, is allowed to propagate without any need to modify the background finite element mesh. The effectiveness of the proposed method has been assessed by simulating mode‐I and mixed‐mode experimental tests. Copyright © 2003 John Wiley & Sons, Ltd.
Synthesis and characterization of phenylethynyl‐end‐capped cooligomides from fluorinated dianhydrides 4,4′‐(hexafluoroisopropylidene)dipthalic anhydride and 4,4′‐(2,2,2‐trifluoro‐1‐phenylethylidene)dipthalic anhydride and para‐ and meta‐phenylene diamines and cooligomide blends with phenylethynyl‐end‐capped reactive diluents
Authors: Liu Hongbo , Simone C. D. , Scola D. A.
Published: July 2003

A series of phenylethynyl (PE)‐end‐capped cooligomides with number‐average molecular weights (Mn) of 4000 and 7000 based on 4,4′‐(hexafluoroisopropylidene)dipthalic anhydride (6FDA) and para‐ and meta‐phenylene diamines containing 80/20 and 70/30 p/m molar ratios in the repeat unit were synthesized and characterized for their thermal and rheological properties. The cooligomides with Mn = 7000 exhibited high melt viscosities with respect to the cooligomides with Mn = 4000 at both 80/20 and 70/30 p/m molar ratios. PE‐end‐capped cooligomides with Mn = 4000 based on 4,4′‐(2,2,2‐trifluoro‐1‐phenylethylidene)dipthalic anhydride (3FDA) and para‐ and meta‐phenylene diamines containing 80/20 and 70/30 p/m ratios in the repeat unit were also investigated. The PE‐6FDA cooligomide, blended with 3,4′‐bis(phenylethynyl)phthalimido diphenylether, exhibited lower viscosities than unblended cooligomides. However, a blend of the 3FDA cooligomide and reactive diluents containing 3FDA exhibited a much lower viscosity than a blend of the 6FDA cooligomide and a reactive diluent containing 6FDA. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2630–2649, 2003
Liquid‐crystalline and light‐emitting polyacetylenes
Authors: Lam Jacky W. Y. , Tang Ben Zhong
Published: July 2003

Rigid polymer backbones have often been considered to be detrimental to the packing of mesogenic pendants, and polyacetylenes have generally been regarded as unpromising materials for light‐emitting applications. Our group, however, has succeeded in creating a series of liquid‐crystalline polyacetylenes with rigid backbones and a variety of light‐emitting polyacetylenes with luminescent chromophores. Here we demonstrate that the rigid polyacetylene skeleton can play a constructive role in guiding the alignments of mesogenic pendants and prove that polyacetylenes can be highly emissive with photoluminescence quantum yields of up to 98% and electroluminescence performances comparable or superior to those of the best blue‐light‐emitting polymers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 41: 2607–2629, 2003