bluuebunny/crossref_metadata_2025_split huggingface dataset:
NLGN3/NLGN4 gene mutations are not responsible for autism in the Quebec population
Authors: Gauthier Julie , Bonnel Anna , St‐Onge Judith , Karemera Liliane , Laurent Sandra , Mottron Laurent , Fombonne Éric , Joober Ridha , Rouleau Guy A. 
Published: June 2004

AbstractJamain [2003: Nat Genet 34:27–29] recently reported mutations in two neuroligin genes in sib‐pairs affected with autism. In order to confirm these causative mutations in our autistic population and to determine their frequency we screened 96 individuals affected with autism. We found no mutations in these X‐linked genes. These results indicate that mutations in NLGN3 and NLGN4 genes are responsible for at most a small fraction of autism cases and additional screenings in other autistic populations are needed to better determine the frequency with which mutations in NLGN3 and NLGN4 occur in autism. © 2004 Wiley‐Liss, Inc.
Positive association of the human frizzled 3 (FZD3) gene haplotype with schizophrenia in Chinese Han population
Authors: Zhang Yanbo , Yu Xin , Yuan Yanbo , Ling Yansu , Ruan Yan , Si Tianmei , Lu Tianlian , Wu Suping , Gong Xiaohong , Zhu Zhongjun , Yang Jianzhong , Wang Fei , Zhang Dai 
Published: June 2004

AbstractFrizzled 3 (FZD3) gene is located on chromosome 8p21, a region that has been implicated in schizophrenia in genetic linkage studies. The FZD3 is a transmembrane receptor required for Wnt signal transduction cascades that have been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Previous work has showed a strong association between FZD3 locus and schizophrenia in family‐based study. To confirm this issue further, we investigated a genetic association between four single nucleotide polymorphisms (SNPs) located in the FZD3 gene and schizophrenia by case‐control study using polymerase chain reaction (PCR)‐based restriction fragment length polymorphism (RFLP) in the Chinese Han population. Our studies showed the SNPs rs2323019 and rs880481 have significant differences in both genotype and allele frequencies between control subjects and schizophrenic patients (rs2323019: Allele A > G, χ2 = 6.7277, df = 1, P = 0.0095; Genotype, χ2 = 10.6583, df = 2, P = 0.0049; rs880481: Allele A > G, χ2 = 10.3945, df = 1, P = 0.0013; Genotype, χ2 = 16.8049, df = 2, P = 0.0002). In addition, we constructed three‐locus haplotypes to test their association with schizophrenia. The globe chi‐squared test for haplotype analysis showed a significant association (χ2 = 66.38, df = 7, P < 0.000001). These results suggested that the FZD3 gene might be involved in the predisposition to schizophrenia. © 2004 Wiley‐Liss, Inc.
Myelin oligodendrocyte glycoprotein (MOG) gene is associated with obsessive‐compulsive disorder
Authors: Zai Gwyneth , Bezchlibnyk Yarema B. , Richter Margaret A. , Arnold Paul , Burroughs Eliza , Barr Cathy L. , Kennedy James L. 
Published: June 2004

AbstractObsessive‐compulsive disorder (OCD) is a severe neuropsychiatric disorder with a strong genetic component, and may involve autoimmune processes. Support for this latter hypothesis comes from the identification of a subgroup of children, described by the term pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections (PANDAS), with onset of OCD symptoms following streptococcal infections. Genes involved in immune response therefore represent possible candidate genes for OCD, including the myelin oligodendrocyte glycoprotein (MOG) gene, which plays an important role in mediating the complement cascade in the immune system. Four polymorphisms in the MOG gene, a dinucleotide CA repeat (MOG2), a tetranucleotide TAAA repeat (MOG4), and 2 intronic single nucleotide polymorphisms, C1334T and C10991T, were investigated for the possibility of association with OCD using 160 nuclear families with an OCD proband. We examined the transmission of alleles of these four polymorphisms with the transmission disequilibrium test (TDT). A biased transmission of the 459‐bp allele (allele 2: χ2 = 5.255, P = 0.022) of MOG4 was detected, while MOG2, C1334T, and C10991T showed no statistically significant bias in the transmission of alleles. The transmission of the C1334T.MOG2.C10991T.MOG4 haplotype 1.13.2.2 (χ2 = 6.426, P = 0.011) was also significant. Quantitative analysis using the family‐based association test (FBAT) was significant for MOG4 in total Yale‐Brown Obsessive‐Compulsive Scale severity score (allele 2: z = 2.334, P = 0.020). Further investigations combining genetic, pathological, and pharmacological strategies, are warranted. © 2004 Wiley‐Liss, Inc.
Regulator of G‐protein signaling 4 (RGS4) gene is associated with schizophrenia in Irish high density families
Authors: Chen Xiangning , Dunham Cynthia , Kendler Seth , Wang Xu , O'Neill F. Anthony , Walsh Dermot , Kendler Kenneth S. 
Published: June 2004

AbstractThe regulator of the G‐protein signaling 4 (RGS4) gene was shown to have a different expression pattern in schizophrenia patients in a microarray study. A family‐based study subsequently implicated the association of this gene with schizophrenia. We replicated the study with our sample from the Irish Study of High Density Schizophrenia Families (ISHDSF). Single marker transmission disequilibrium tests (TDT) for the four core SNPs showed modest association for SNP 18 (using a narrow diagnostic approach with FBAT P = 0.044; with PDT P = 0.0073) and a trend for SNP 4 (with FBAT P = 0.1098; with PDT P = 0.0249). For SNP 1 and 7, alleles overtransmitted to affected subjects were the same as previously reported. Haplotype analyses suggested that haplotype G‐G‐G for SNP1–4–18, which is the most abundant haplotype (42.3%) in the Irish families, was associated with the disease (narrow diagnosis, FBAT P = 0.0061, PDT P = 0.0498). This was the same haplotype implicated in the original study. While P values were not corrected for multiple testing because of the clear prior hypothesis, these results could be interpreted as supporting evidence for the association between RGS4 and schizophrenia. © 2004 Wiley‐Liss, Inc.
Diffuse axonal injury in children: Clinical correlation with hemorrhagic lesions
Authors: Tong Karen A. , Ashwal Stephen , Holshouser Barbara A. , Nickerson Joshua P. , Wall Christopher J. , Shutter Lori A. , Osterdock Renatta J. , Haacke E. M. , Kido Daniel 
Published: June 2004

AbstractAn inception cohort of 40 children and adolescents with traumatic brain injury and suspected diffuse axonal injury were studied using a new high‐resolution magnetic resonance imaging susceptibility‐weighted technique that is very sensitive for hemorrhage. A blinded comparison was performed between the extent of parenchymal hemorrhage and initial clinical variables as well as outcomes measured at 6 to 12 months after injury. Children with lower Glasgow Coma Scale scores (≤8, n = 30) or prolonged coma (>4 days, n = 20) had a greater average number (p = 0.007) and volume (p = 0.008) of hemorrhagic lesions. Children with normal outcomes or mild disability (n = 30) at 6 to 12 months had, on average, fewer hemorrhagic lesions (p = 0.003) and lower volume (p = 0.003) of lesions than those who were moderately or severely disabled or in a vegetative state. Significant differences also were observed when comparing regional injury to clinical variables. Because susceptibility‐weighted imaging is much more sensitive than conventional T2*‐weighted gradient‐echo sequences in detecting hemorrhagic diffuse axonal injury, more accurate and objective assessment of injury can be obtained early after insult, and may provide better prognostic information regarding duration of coma as well as long‐term outcome. Ann Neurol 2004;56:36–50
Human T‐lymphotropic virus type II and neurological disease
Authors: Araujo Abelardo , Hall William W. 
Published: June 2004

AbstractHuman T‐lymphotropic virus type I (HTLV‐I) and type II (HTLV‐II) are closely related retroviruses with similar biological properties and common modes of transmission. HTLV‐I infection is endemic in well‐defined geographic regions, and it is estimated that some 20 million individuals are infected worldwide. Although most infected individuals are asymptomatic carriers, some 2 to 5% will develop a chronic encephalomyelopathy, HTLV‐I–associated myelopathy/tropical spastic paraparesis (HAM/TSP). In contrast with HTLV‐I, the role of HTLV‐II in the development of neurological disorders is much less clear. HTLV‐II is endemic in many native Amerindian groups and epidemic in injecting drug users (IDUs) worldwide. To evaluate the role of HTLV‐II in neurological disease, we have critically reviewed all reported cases of HTLV‐II–associated disorders. This has confirmed that although rare infection is associated with a disorder clinically similar or identical to HAM/TSP. However, most reports that have attributed infection to a range of other neurological disorders are difficult to evaluate in that in many cases either the association appears to be fortuitous or the presentations were confounded by a background of concomitant human immunodeficiency virus–1 infection and/or active IDU. In view of the many HTLV‐II–infected individuals in urban areas of North America and Europe, neurologists should be aware of the potential clinical consequences of this infection.
Prevention of neuropathology in the mouse model of hurler syndrome
Authors: Desmaris Nathalie , Verot Lucie , Puech Jean Philippe , Caillaud Catherine , Vanier Marie Thérèse , Heard Jean Michel 
Published: June 2004

AbstractA defect of the lysosomal enzyme α‐L‐iduronidase (IDUA) interrupts heparan and dermatan sulfate degradation and causes neuropathology in children with severe forms of mucopolysaccharidosis type I (MPSI, Hurler syndrome). Enzyme substitution therapy is beneficial but ineffective on the central nervous system. We could deliver the missing enzyme to virtually the entire brain of MPSI mice through a single injection of gene transfer vectors derived from adenoassociated virus serotype 2 (AAV2) or 5 (AAV5) coding for human IDUA. This result was reproducibly achieved with both vector types in 46 mice and persisted for at least 26 weeks. Success was more frequent, enzyme activity was higher, and corrected areas were broader with AAV5 than with AAV2 vectors. Treatment presumably reversed and certainly prevented the accumulation of GM2 and GM3 gangliosides, which presumably participates to neuropathology. Lysosomal distension, which already was present at the time of treatment, had disappeared from both brain hemispheres and was minimal in the cerebellum in mice analyzed 26 weeks after injection. This study shows that pathology associated with MPSI can be prevented in the entire mouse brain by a single AAV vector injection, providing a preliminary evaluation of the feasibility of gene therapy to stop neuropathology in Hurler syndrome. Ann Neurol 2004;56:68–76
Long‐term effect of motor cortical repetitive transcranial magnetic stimulation induces
Authors: Hayashi Takuya , Ohnishi Takashi , Okabe Shingo , Teramoto Noboru , Nonaka Yukio , Watabe Hiroshi , Imabayashi Etsuko , Ohta Yoichiro , Jino Hiroshi , Ejima Norimasa , Sawada Tohru , Iida Hidehiro , Matsuda Hiroshi , Ugawa Yoshikazu 
Published: June 2004

AbstractRepetitive transcranial magnetic stimulation (rTMS) recently has been assessed as a noninvasive treatment modality for movement and psychiatric disorders, whereas the mechanism underlying the therapeutic effects is not fully understood. Studies in rodents showed lasting functional changes in some selected regions, such as limbic‐associated structures, but unfocused brain stimulation did not clarify the regional effects. To address the topographical and temporal profiles of the effects on glucose metabolism in primate brain, we performed rTMS and repeated 18F‐fluorodeoxyglucose positron emission tomography (FDG‐PET) before, during, and up to 16 days after rTMS in anesthetized cynomologous monkeys. We delivered a total of 2,000 pulses of 5Hz‐rTMS over the right precentral gyrus using a small‐sized eight‐figured coil that induced a localized electrical field. Voxel‐based analysis in a standard space of the macaque brain showed statistically robust changes in FDG uptake: a decrease in the motor/premotor cortices and an increase in the limbic‐associated areas involving the anterior/posterior cingulate, and orbitofrontal cortices. Interestingly, these uptake changes continued for at least 8 days and the magnitude of the lasting effects in the limbic‐related areas was negatively correlated across subjects with those in the motor/premotor cortices. The results demonstrate that motor rTMS has a long‐term lasting effect on motor‐related regions and distant limbic‐related areas via functional connections.
Is benign rolandic epilepsy genetically determined?
Authors: Vadlamudi Lata , Harvey A. Simon , Connellan Mary M. , Milne Roger L. , Hopper John L. , Scheffer Ingrid E. , Berkovic Samuel F. 
Published: June 2004

AbstractBenign rolandic epilepsy (BRE) is considered to be a genetically determined idiopathic partial epilepsy. We studied twins with BRE and compared the concordance with a twin sample of idiopathic generalized epilepsy (IGE). All eight BRE pairs (six monozygous [MZ], two dizygous [DZ]) were discordant. MZ pairwise concordance was 0 (95% confidence interval [CI], 0–0.4) for BRE compared with 0.7 (95% CI, 0.5–0.9) for 26 IGE MZ pairs. Our data suggest that conventional genetic influences in BRE are considerably less than for IGE, and other mechanisms need to be explored. Ann Neurol 2004;56:129–132
Heterogeneity of nemaline myopathy cases with skeletal muscle α‐actin gene mutations
Authors: Agrawal Pankaj B. , Strickland Corinne D. , Midgett Charles , Morales Ana , Newburger Daniel E. , Poulos Melisa A. , Tomczak Kinga K. , Ryan Monique M. , Iannaccone Susan T. , Crawford Tom O. , Laing Nigel G. , Beggs Alan H. 
Published: June 2004

AbstractNemaline myopathy (NM) is the most common of several congenital myopathies that present with skeletal muscle weakness and hypotonia. It is clinically heterogeneous and the diagnosis is confirmed by identification of nemaline bodies in affected muscles. The skeletal muscle α‐actin gene (ACTA1) is one of five genes for thin filament proteins identified so far as responsible for different forms of NM. We have screened the ACTA1 gene in a cohort of 109 unrelated patients with NM. Here, we describe clinical and pathological features associated with 29 ACTA1 mutations found in 38 individuals from 28 families. Although ACTA1 mutations cause a remarkably heterogeneous range of phenotypes, they were preferentially associated with severe clinical presentations (p < 0.0001). Most pathogenic ACTA1 mutations were missense changes with two instances of single base pair deletions. Most patients with ACTA1 mutations had no prior family history of neuromuscular disease (24/28). One severe case, caused by compound heterozygous recessive ACTA1 mutations, demonstrated increased α‐cardiac actin expression, suggesting that cardiac actin might partially compensate for ACTA1 abnormalities in the fetal/neonatal period. This cohort also includes the first instance of an ACTA1 mutation manifesting with adult‐onset disease and two pedigrees exhibiting potential incomplete penetrance. Overall, ACTA1 mutations are a common cause of NM, accounting for more than half of severe cases and 26% of all NM cases in this series. Ann Neurol 2004;56:86–96
Persistent NKH with transient or absent symptoms and a homozygous GLDC mutation
Authors: Korman Stanley H. , Boneh Avihu , Ichinohe Akiko , Kojima Kanako , Sato Kenichi , Ergaz Zivanit , Gomori John M. , Gutman Alisa , Kure Shigeo 
Published: June 2004

AbstractThree of four nonketotic hyperglycinemia patients homozygous for a novel GLDC mutation (A802V) were treated by assisted respiration and/or sodium benzoate with or without ketamine and had transient neonatal or absent symptoms and normal developmental outcome, despite persisting biochemical evidence of nonketotic hyperglycinemia. This exceptional outcome may be related to the high residual activity of the mutant protein (32% of wild type) and therapeutic intervention during a critical period of heightened brain exposure and sensitivity to glycine. Ann Neurol 2004;56:139–143
MR molecular imaging of early endothelial activation in focal ischemia
Authors: Barber Philip A. , Foniok Tadeusz , Kirk David , Buchan Alastair M. , Laurent Sophie , Boutry Sébastien , Muller Robert N. , Hoyte Lisa , Tomanek Boguslaw , Tuor Ursula I. 
Published: June 2004

AbstractFocal ischemia followed by reperfusion initiates a harmful P‐ and E‐selectin–mediated recruitment of leukocytes in brain microvasculature. In this study, we tested whether a novel magnetic resonance (MR) contrast agent (Gd‐DTPA‐sLex A), which is designed to bind to activated endothelium could be detected by MR imaging (MRI) in a focal stroke mouse model. MRIs (9.4T) of the brain were acquired 24 hours after transient middle cerebral artery occlusion. T1 maps were acquired repeatedly before and up to 1.5 hours after the intravenous injection of either Gd‐DTPA or Gd‐DTPA‐sLex A. Analysis of images included a pixel‐by‐pixel subtraction of T1 maps from the precontrast T1 maps and quantification of T1 within the ischemic area. After injection of Gd‐DTPA‐sLex A, T1 decreased compared with precontrast levels, and an interhemispheric difference between the pre–post contrast T1 developed within the stroke lesion at a mean time of 52 minutes after injection (p < 0.05). Animals injected with Gd‐DTPA did not exhibit changes in T1 signal intensity between regions of the ipsilateral and contralateral hemispheres, indicating that the reductions in T1 observed with Gd‐DTPA‐sLex A were unrelated to blood–brain barrier breakdown. Fluorescent‐labeled sLex A administered intravenously was observed to bind to the endothelium of injured but not control brain. The study suggests that the contrast agent Gd‐DTPA‐sLex A can be used to visualize early endothelial activation after transient focal ischemia in vivo with MRI. Ann Neurol 2004;56:116–120
High‐frequency oscillations recorded in human medial temporal lobe during sleep
Authors: Staba Richard J. , Wilson Charles L. , Bragin Anatol , Jhung Donald , Fried Itzhak , Engel Jerome 
Published: June 2004

AbstractThe presence of fast ripple oscillations (FRs, 200–500Hz) has been confirmed in rodent epilepsy models but has not been observed in nonepileptic rodents, suggesting that FRs are associated with epileptogenesis. Although studies in human epileptic patients have reported that both FRs and ripples (80–200Hz) chiefly occur during non–rapid eye movement sleep (NREM), and that ripple oscillations in human hippocampus resemble those found in nonprimate slow wave sleep, quantitative studies of these oscillations previously have not been conducted during polysomnographically defined sleep and waking states. Spontaneous FRs and ripples were detected using automated computer techniques in patients with medial temporal lobe epilepsy during sleep and waking, and results showed that the incidence of ripples, which are thought to represent normal activity in animal and human hippocampus, was similar between epileptogenic and nonepileptogenic temporal lobe, whereas rates of FR occurrence were significantly associated with epileptogenic areas. The generation of both FRs and ripples showed the highest rates of occurrence during NREM sleep. During REM sleep, ripple rates were lowest, whereas FR rates remained elevated and were equivalent to rates observed during waking. The predominance of FRs within the epileptogenic zone not only during NREM sleep, but also during epileptiform‐suppressing desynchronized episodes of waking and REM sleep supports the view that FRs are the product of pathological neuronal hypersynchronization associated with seizure‐generating areas. Ann Neurol 2004;56:108–115
Hadamard Transform Time‐of‐Flight Mass Spectrometry: More Signal, More of the Time
Authors: Zare Richard N. , Fernández Facundo M. , Kimmel Joel R. 
Published: June 2004

AbstractHadamard transform time‐of‐flight mass spectrometry (HT‐TOF MS) is a type of mass analysis that was developed to couple continuous ion sources to the inherently pulsed nature of time‐of‐flight measurements. Unlike conventional TOF MS, the Hadamard transform method offers a duty cycle of 50 %, with the possibility of extending it to 100 %. Because it is a multiplexing technique, the attainable signal‐to‐noise ratio (SNR) is also significantly higher than that of conventional TOF MS. This review covers the basic principles behind HT‐TOF MS. We illustrate, through examples, the source of the high‐duty cycle and the increase in SNR. These features translate to a mass spectral storage rate that is the fastest among similar instruments, which enables its use as a detector for high‐speed separations.
Gelsemine: A Thought‐Provoking Target for Total Synthesis
Authors: Lin Hong , Danishefsky Samuel J. 
Published: June 2004

AbstractGelsemine and 21‐oxogelsemine have been synthesized through several routes. This Review focuses on the comparison of the different strategies to assemble the bicyclo[3.2.1]octane core, to introduce the bridgehead quaternary C20 to form the pyrrolidine moiety, to construct the oxindole residue, and to close the tetrahydropyran ring en route to gelsemine.
Polymerization conversion and structure of magnesium methacrylate in ethylene–vinyl acetate rubber vulcanizates
Authors: Du Aihua , Peng Zonglin , Zhang Yong , Zhang Yinxi 
Published: June 2004

AbstractEthylene–vinyl acetate rubber (EVM) filled with magnesium methacrylate (MDMA) was cured with dicumyl peroxide (DCP). The experimental results showed that the mechanical properties of MDMA/EVM vulcanizates were superior to those of high‐abrasion furnace carbon black/EVM vulcanizates. The tensile strength of the MDMA/EVM vulcanizate could reach 22.5 MPa and the tear strength was 83.5 kN/m, whereas its elongation at break remained over 300%, even when the MDMA content was 50 phr. FTIR analysis confirmed that polymerization of MDMA occurred under the initiation of DCP, and the polymerization conversion of MDMA decreased with the increase of MDMA content. When the MDMA content increased from 10 to 50 phr, the conversion of MDMA in EVM decreased from 68 to 20%. SEM and TEM observations indicated that 20 μm particles of MDMA powder changed into about 20 nm particles during the curing process, and the finer particles dispersed evenly in the EVM vulcanizates. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2379–2384, 2004
The effect of paraffin on fiber dispersion and mechanical properties of polyolefin–sawdust composites
Authors: Viksne Armanda , Rence Ligita , Kalnins Martins , Bledzki Andzej K. 
Published: June 2004

AbstractThis article reports on the influence of the paraffin (PAR) on the wood fiber (WF) dispersion in different polyethylene (low‐density polyethylene, high‐density polyethylene, recycled polyethylene) matrices, as well as on the melt flow behavior and mechanical properties of WF‐reinforced polyethylene (PE) composites. In the presence of paraffin, the composites showed improved tensile and flexural strength and modulus, but lower impact strength and elongation at break. The extent of improvement in mechanical properties depends on paraffin content and type of polyethylene; the most effective paraffin was in LDPE‐based composites. Paraffin‐treated WF showed lower moisture absorption ability in comparison with unmodified wood fiber. The phase segregation process was investigated for PE/PAR blends by DSC method. It was shown that an increase of paraffin concentration in the PE/PAR blend leads to a decrease of PE melting temperature and an increase of paraffin melting temperature; it indicates a net exchange of material from paraffin towards polyethylene. However, generally both components of PE/PAR blends remain immiscible. © 2004 Wiley Periodicals, Inc. J Appl Polym Sci 93: 2385–2393, 2004