bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation between cerebral MRI abnormalities and mental retardation in patients with mucopolysaccharidoses
Authors: Gabrielli Orazio , Polonara Gabriele , Regnicolo Luana , Petroni Valeria , Scarabino Tommaso , Coppa Giovanni V. , Salvolini Ugo 
Published: February 2004

AbstractMucopolysaccharidoses (MPSs) are a group of inherited disorders due to lysosomal enzyme deficiencies which lead to multi‐organ accumulation of glycosaminoglycans. Some forms of MPS disorders are characterized by various degrees of mental retardation. Magnetic Resonance Imaging (MRI) is the primary imaging technique to detect CNS alterations. The aim of this study is to evaluate the correlation between white matter (WM) alterations and the presence of mental retardation. We analyzed 20 patients with different forms of MPSs, 11 with mental retardation and 9 with a normal cognitive function; all of them underwent brain MRI and received a score on the basis of the alterations (WM alterations; perivascular, subarachnoid, and ventricular space enlargement; abnormalities of the basal ganglia, of the corpus callosum and of the atlanto‐axial joint). All patients with mental retardation presented severe WM alterations, while only five out of the nine subjects without mental retardation showed certainly WM abnormalities. As far as the other cerebral abnormalities are concerned, no difference between the two groups has been found. These data seem to show that there is a significant correlation between the presence of WM alterations and mental retardation. © 2003 Wiley‐Liss, Inc.
Limb deficiency defects, MSX1, and exposure to tobacco smoke
Authors: Carmichael Suzan L. , Shaw Gary M. , Yang Wei , Lammer Edward J. , Zhu Huiping , Finnell Richard H. 
Published: February 2004

AbstractThere is increasing evidence from epidemiologic studies that genetic susceptibilities may modify the teratogenic effects of smoking. A previous study suggested that maternal smoking in the presence of a dinucleotide repeat polymorphism for MSX1 produced an almost fivefold increased risk for limb anomalies, providing evidence for a gene–environment interaction. The current study examined this potential interaction, using case‐control data with several methodologic improvements, including a larger sample size and more detailed information on cigarette smoke exposures. Cases (n = 92) were ascertained from pregnancies ending in 1987–1989, and controls (n = 180) were randomly selected from eligible liveborn infants. In telephone interviews, women reported smoking behaviors during the month before pregnancy through the end of the first trimester. Odds ratios (OR) for maternal and paternal smoking ranged from 1.0 to 1.4, risk estimates were imprecise; for example, the OR for maternal smoking ≥20 cigarettes per day, versus none, was 1.3 (95% confidence interval (CI) 0.5–3.4). Relative to the homozygous wildtype, the OR was 1.5 (95% CI 0.7–3.5) for the homozygous variant genotype and 0.8 (95% CI 0.5–1.4) for the heterozygous variant genotype. There was no evidence that maternal smoking or both parents smoking, in combination with a susceptible MSX1 genotype, conferred an additional increase in risk of limb defects. This study did not find a gene–environment interaction between maternal smoking, infant MSX1 CA repeat polymorphism, and risk of limb deficiency defects. This finding contrasts with results of a previous study, which provided initial evidence for such an interaction. Several important methodological differences may have contributed to the differences in findings between the two studies. © 2003 Wiley‐Liss, Inc.
Dyschromatosis universalis hereditaria: Familial case and ultrastructural skin investigation
Authors: Nuber Ulrike A. , Tinschert Sigrid , Mundlos Stefan , Hauber Ingrid 
Published: February 2004

AbstractWe report a familial case of dyschromatosis universalis hereditaria (DUH) which is compatible with an autosomal dominant inheritance. The male proband from Bangladesh presented with randomly distributed hyper‐ and hypo‐pigmented skin lesions of variable shape and size with a mottled appearance. Three additional members of the non‐consangineous family are similarly affected. Light and electron microscopy show normal numbers of active melanocytes, but different amounts of fully melanized melanosomes in hyper‐pigmented and hypo‐pigmented macules. Our findings indicate that DUH is not a disorder of number. It appears to be a disorder of melanosome synthesis rate or in addition melanocyte activity. © 2003 Wiley‐Liss, Inc.
Focal caspase activation underlies the endplate myopathy in slow‐channel syndrome
Authors: Vohra Bhupinder P. S. , Groshong Jason S. , Maselli Ricardo A. , Verity M. Anthony , Wollmann Robert L. , Gomez Christopher M. 
Published: February 2004

AbstractSlow‐channel syndrome (SCS) is a progressive neuromuscular disorder caused by abnormal gating of mutant acetylcholine receptors (AChRs) in the neuromuscular junction (NMJ). The pathological hallmark is selective degeneration of the NMJ termed endplate myopathy. Endplate myopathy consists of a combination of ultrastructural abnormalities, including degenerating subsynaptic nuclei, mitochondria, and postsynaptic folds, caused by localized cation overload through mutant AChRs. Because some of these changes resemble those seen in programmed cell death, we evaluated SCS muscle for evidence of focal activation of apoptotic pathways. Using antisera specific for the activated forms of caspases, the family of cysteine proteases that underlies apoptosis, we demonstrated that active forms of initiator and effector caspases are selectively localized at the NMJ in SCS. In comparison with an electron microscopic assessment of the abnormalities seen in endplate myopathy, we found that activated caspases were present at between 15 and 57% of endplates, similar to the proportion of endplates with degenerating mitochondria or vacuoles. This greatly exceeds the number of NMJs exhibiting nuclear degeneration. These findings provide the first evidence supporting the view that caspase activation in human disease can play a prominent role in localized cellular degenerative processes without causing nuclear or cell death.
Changing incidence of central nervous system diseases in the EuroSIDA cohort
Authors: d'Arminio Monforte Antonella , Cinque Paola , Mocroft Amanda , Goebel Frank‐Detlev , Antunes Francisco , Katlama Christine , Stenz Justesen Ulrik , Vella Stefano , Kirk Ole , Lundgren Jens 
Published: February 2004

AbstractA drastic decrease in incidence has been observed for most human immunodeficiency virus (HIV)–related opportunistic manifestations after use of highly active antiretroviral therapy (HAART). We assessed the trend of incidence of central nervous system (CNS) diseases in a prospective multicenter observational study involving 9,803 patients across Europe in the period 1994 to 2002 and analyzed patient and treatment variables associated with these conditions. Overall, 568 patients (5.8%) received a diagnosis of a new CNS disease. Incidence decreased significantly from 5.9 per 100 person‐year in 1994 to 0.5 in 2002. Overall, the decrease was 40% per calendar year, and it was similar to that of non‐CNS diseases and less evident after year 1998. In multivariable models, low CD4 cell count and high plasma viral load, but not HAART or calendar year, were significantly associated with risk to develop CNS disease, indicating that the effect of HAART was likely mediated by both improved immunological conditions and inhibition of viral replication. In contrast, use of nucleoside reverse transcriptase inhibitors, irrespective of use of protease inhibitors or non‐nucleoside reverse transcriptase inhibitors, appeared to protect specifically against acquired immunodeficiency disease syndrome dementia complex, suggesting that, in this condition, therapy might have a direct, additive effect in the CNS.
Hormonal regulation of atypical absence seizures
Authors: Persad Vasan , Ting Wong C. Guin , Cortez Miguel A. , Wang Yu Tian , Snead O. Carter 
Published: February 2004

AbstractA time course study that examined the effects of the female estrous cycle on the chronic slow spike‐and‐wave discharges (SSWDs), γ‐aminobutyric B receptor (GABABR) binding, and GABABR protein expression was conducted in Long Evans hooded rats treated during development with a cholesterol synthesis inhibitor AY9944 (AY). In addition, a pharmacological study using the hormones progesterone, 17 β‐estradiol, mifepristone (intracellular progesterone receptor antagonist), tamoxifen (intracellular estrogen receptor antagonist), and allopregnanolone (progesterone metabolite) was performed to determine their effects on AY‐induced seizures. The data indicate that there is a significant increase in both the duration of SSWD and GABABR binding in the AY model, during the proestrus stage of the estrous cycle, the stage during which the levels of progesterone are at their highest. No changes in GABABR1a or R2 protein levels were observed. In addition, the administration of both progesterone and allopregnanolone exacerbated seizures in the AY model, whereas 17 β‐estradiol attenuated the SSWD duration. Neither mifepristone nor tamoxifen blocked the effects of progesterone and 17 β‐estradiol, respectively, on SSWD duration in the AY model, suggesting that these two sex hormones are working in a manner independent of their intracellular receptors. These data suggest an important role for steroid hormones in the regulation and maintenance of AY‐induced atypical absence seizures.
Circadian rhythm of restless legs syndrome: Relationship with biological markers
Authors: Michaud Martin , Dumont Marie , Selmaoui Brahim , Paquet Jean , Livia Fantini Maria , Montplaisir Jacques 
Published: February 2004

AbstractRecently, it was suggested that the intensity of restless legs syndrome (RLS) symptoms may be modulated by a circadian factor. The objective of this study was to evaluate, during a 28‐hour modified constant routine, the nycthemeral or circadian variations in subjective leg discomfort and periodic leg movements (PLMs) and to parallel these changes with those of subjective vigilance, core body temperature, and salivary melatonin. Seven patients with primary RLS and seven healthy subjects matched for sex and age entered this study. Although the symptoms were more severe in patients than in controls, a significant circadian variation in leg discomfort and PLM (p < 0.01) was found for both groups. In both groups, the profiles of leg discomfort and PLM were significantly correlated with those of subjective vigilance, core body temperature, and salivary melatonin. However, among these variables, the changes in melatonin secretion were the only ones that preceded the increase in sensory and motor symptoms in RLS patients. This result and those of others studies showing that melatonin exerts an inhibitory effect on central dopamine secretion suggest that melatonin might be implicated in the worsening of RLS symptoms in the evening and during the night.
HIV‐1 inhibits long‐term potentiation and attenuates spatial learning
Authors: Li Sheng‐Tian , Matsushita Masayuki , Moriwaki Akiyoshi , Saheki Yasunori , Lu Yun‐Fei , Tomizawa Kazuhito , Wu Hai‐Yan , Terada Hiroaki , Matsui Hideki 
Published: February 2004

AbstractAlthough memory deficits have been clearly documented in patients with human immunodeficiency virus type‐1 (HIV‐1) infection, the physiological basis of this dysfunction is poorly understood. We focused on Tat, a viral protein released from HIV‐1–infected cells and investigated its effect on spatial learning in adult mice. An intracerebroventricular injection of Tat leads to attenuation of spatial learning accompanied by suppression of long‐term potentiation (LTP), the cellular basis of spatial learning, in hippocampal cornu ammonis 1 pyramidal neurons. Tat facilitates extrasynaptic but not synaptic N‐methyl‐D‐aspartate (NMDA) receptor activity. Taken together, these data provide strong evidence that the Tat pathway underlies the development of memory dysfunction in patients with HIV‐1 infection and suggest a causal relationship between Tat, the facilitation of extrasynaptic NMDA receptor activity, inhibition of LTP, and attenuation of spatial learning.
Influence of interhemispheric interactions on motor function in chronic stroke
Authors: Murase Nagako , Duque Julie , Mazzocchio Riccardo , Cohen Leonardo G. 
Published: February 2004

AbstractIn patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1intact hemisphere) may influence functional recovery, possibly through transcallosal effects exerted over M1 in the lesioned hemisphere (M1lesioned hemisphere). Here, we studied interhemispheric inhibition (IHI) between M1intact hemisphere and M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but remained deep in patients, a finding that correlated with poor motor performance. These results document an abnormally high interhemispheric inhibitory drive from M1intact hemisphere to M1lesioned hemisphere in the process of generation of a voluntary movement by the paretic hand. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke, an interpretation consistent with models of interhemispheric competition in motor and sensory systems.
Irradiation attenuates neurogenesis and exacerbates ischemia‐induced deficits
Authors: Raber Jacob , Fan Yang , Matsumori Yasuhiko , Liu Zhengyan , Weinstein Philip R. , Fike John R. , Liu Jialing 
Published: February 2004

AbstractIncreased neurogenesis after cerebral ischemia suggests that functional recovery after stroke may be attributed, in part, to neural regeneration. In this study, we investigated the role of neurogenesis in the behavioral performance of gerbils after cerebral global ischemia. We used ionizing radiation to decrease neural regeneration, and 2 weeks later cerebral global ischemia was induced by bilateral common carotid artery occlusion. One month after the occlusion, the animals were behaviorally tested. Irradiation alone reduced neurogenesis but did not change vascular or dendritic morphology at the time of behavioral testing. Neither did irradiation, ischemia, or combined treatment impair rotor‐rod performance or alter open‐field activity. Gerbils subjected to both irradiation and ischemia demonstrated impaired performance in the water‐maze task, compared with those that received only ischemia, radiation, or no treatment. These impairments after cerebral global ischemia under conditions of reduced neurogenesis support a role for the production of new cells in mediating functional recovery.
Blood transcriptional signatures of multiple sclerosis: Unique gene expression of disease activity
Authors: Achiron Anat , Gurevich Michael , Friedman Nir , Kaminski Naftali , Mandel Mathilda 
Published: February 2004

AbstractMultiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T‐cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote‐target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Authors: Klunk William E. , Engler Henry , Nordberg Agneta , Wang Yanming , Blomqvist Gunnar , Holt Daniel P. , Bergström Mats , Savitcheva Irina , Huang Guo‐Feng , Estrada Sergio , Ausén Birgitta , Debnath Manik L. , Barletta Julien , Price Julie C. , Sandell Johan , Lopresti Brian J. , Wall Anders , Koivisto Pernilla , Antoni Gunnar , Mathis Chester A. , Långström Bengt 
Published: February 2004

AbstractThis report describes the first human study of a novel amyloid‐imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound‐B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94‐fold, p = 0.0001). Large increases also were observed in parietal (1.71‐fold, p = 0.0002), temporal (1.52‐fold, p = 0.002), and occipital (1.54‐fold, p = 0.002) cortex and the striatum (1.76‐fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 ± 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F‐fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = −0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.
Involvement of medullary serotonergic groups in multiple system atrophy
Authors: Benarroch Eduardo E. , Schmeichel Ann M. , Low Phillip A. , Parisi Joseph E. 
Published: February 2004

AbstractWe sought to determine whether medullary serotonergic neurons were affected in multiple system atrophy (MSA). Immunostaining for tryptophan hydroxylase was performed on serial 50μm sections of the medulla of brains obtained at autopsy from six control subjects, eight subjects with clinical diagnosis of MSA, and four with Parkinson's disease. There was a severe depletion of serotonergic neurons in the nucleus raphe magnus, raphe obscurus, raphe pallidus, and ventrolateral medulla in MSA. Depletion of serotonergic neurons may contribute to impaired control of sympathetic outflow and other abnormalities in MSA. Ann Neurol 2004
CYP2D6 polymorphism, pesticide exposure, and Parkinson's disease
Authors: Elbaz Alexis , Levecque Clotilde , Clavel Jacqueline , Vidal Jean‐Sébastien , Richard Florence , Amouyel Philippe , Alpérovitch Annick , Chartier‐Harlin Marie‐Christine , Tzourio Christophe 
Published: February 2004

AbstractWe performed a case–control study of Parkinson's disease (PD) in a population characterized by a high prevalence of pesticide exposure and studied the joint effect of pesticide exposure and CYP2D6. Although they are based on a small group of subjects with the joint exposure, our findings are consistent with a gene–environment interaction disease model according to which (1) pesticides have a modest effect in subjects who are not CYP2D6 poor metabolizers, (2) pesticides' effect is increased in poor metabolizers (approximately twofold), and (3) poor metabolizers are not at increased PD risk in the absence of pesticide exposure. Ann Neurol 2004
A functional polymorphism regulating dopamine β‐hydroxylase influences against Parkinson's disease
Authors: Healy Daniel G. , Abou‐Sleiman Patrick M. , Ozawa Tetsutaro , Lees Andrew J. , Bhatia Kailash , Ahmadi Kourosh R. , Wullner Ullrich , Berciano Jose , Moller J. Carsten , Kamm Christoph , Burk Katrin , Barrone Paolo , Tolosa Eduardo , Quinn Niall , Goldstein David B. , Wood Nicholas W. 
Published: February 2004

AbstractA functional −1021C → T polymorphism in the dopamine β‐hydroxylase gene has been demonstrated to regulate plasma DBH activity. We report that individuals with genetically determined low serum DBH activity (genotype T/T) have protection against Parkinson's disease (p = 0.01). In particular, we observed an underrepresentation of the T/T genotype odds ratio = 0.46 (CI = 0.27‐0.8). Rather than identifying a haplotype, or a marker in linkage disequilibrium with the risk variant, this to our knowledge is the first report directly linking PD susceptibility with a proven functional variant. Ann Neurol 2004
Pael‐R is accumulated in Lewy bodies of Parkinson's disease
Authors: Murakami Tetsuro , Shoji Mikio , Imai Yuzuru , Inoue Haruhisa , Kawarabayashi Takeshi , Matsubara Etsuro , Harigaya Yasuo , Sasaki Atsushi , Takahashi Ryosuke , Abe Koji 
Published: February 2004

AbstractWe examined the distribution of Pael‐R, a newly identified substrate for Parkin, in Parkinson's disease (PD) and multiple system atrophy (MSA). Pael‐R, Parkin, α‐synuclein, and ubiquitin accumulated in Lewy bodies (LBs) and neurites. Pael‐R was localized in the core of LBs. Parkin and α‐synuclein accumulated in the halo, neuronal cell bodies, and processes. These findings potentially suggest the involvement of Pael‐R in LB formation, and protection role of Parkin in Pael‐R‐mediated neurotoxicity in PD. The absence of Pael‐R and Parkin in glial cytoplasmic inclusions (GCIs) in MSA implies a distinct pathway involved in the formation of LBs and GCIs. Ann Neurol 2004
Synthese und Eigenschaften allenischer Natur‐ und Wirkstoffe
Authors: Hoffmann‐Röder Anja , Krause Norbert 
Published: February 2004

AbstractHeute sind etwa 150 Naturstoffe mit Allen‐ oder Cumulen‐Struktur bekannt. Die Chemie dieser Verbindungen hat sich als ein reizvolles und fruchtbares Gebiet erwiesen: Fortschritte in der Isolierung und Charakterisierung neuer allenischer Naturstoffe haben zur Etablierung effizienter Syntheseverfahren geführt, die häufig einen Zugang zu enantiomerenreinen Produkten eröffneten. Wegen der oftmals beeindruckenden biologischen Eigenschaften allenischer Naturstoffe sind Allengruppierungen mittlerweile systematisch in pharmakologisch aktive Verbindungsklassen (Steroide, Prostaglandine, Aminosäuren, Nucleoside) eingebaut worden. Diese funktionalisierten Allene weisen in vielen Fällen interessante Aktivitäten auf, beispielsweise als Mechanismus‐inhärente Enzyminhibitoren, Cytostatika oder antivirale Wirkstoffe. Eine grundlegende Voraussetzung für weitere Entwicklungen auf diesem Gebiet ist die effiziente stereoselektive Synthese von Allenderivaten.
Crystallographic report: Bis[bis(N,N‐dibenzyldithiocarbamato)cadmium(II)]
Authors: Yin Xia , Zhang Weiguang , Zhang Qijiao , Fan Jun , Lai Chian Sing , Tiekink Edward R. T. 
Published: February 2004

AbstractThe centrosymmetric structure of {Cd[S2CN(CH2Ph)2]2}2 features both bridging and chelating dithiocarbamate ligands so that a square pyramidal S5 coordination geometry results. Copyright © 2004 John Wiley & Sons, Ltd.