bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemisorption of n-Butylamine and n-Butylmercaptan on Fluoride-Modified CoMo/Al2O3 Catalysts
Authors: Sarbak Z. , Pogorzelska A.
Published: March 2003

The chemisorption of n-butylamine (n-BA) and n-butylmercaptan (n-BM) on cobalt–molybdenum catalysts supported on alumina containing fluoride ions was studied. The active phases of the catalysts were introduced in two ways: either simultaneously or in two stages. It was shown that the chemisorption of n-BA increased with increasing concentration of fluoride ions, but no such relationship was observed for n-BM. The sequence in which fluoride ions and CoMo were introduced had no significant effect on the effectiveness of chemisorption.
Syndromic form of X‐linked mental retardation with marked hypotonia in early life, severe mental handicap, and difficult adult behavior maps to Xp22
Authors: Turner Gillian , Gedeon Agi , Kerr Bronwyn , Bennett Rachael , Mulley John , Partington Michael
Published: February 2003

An X‐linked recessive syndromic form of mental retardation is described in a family in which 10 males in four generations were affected. The main manifestations were severe to profound intellectual disability, muscular hypotonia in childhood, delayed walking, and difficult, aggressive behavior. There was a moderate reduction both in occipitofrontal circumference (OFC) and height and a similar facial appearance, triangular in shape with a high forehead, prominent ears, and a small pointed chin. Linkage analysis located the gene at Xp22 with maximum lod scores of 4.8 at θ = 0.0 for markers mapping between the closest recombination points at DXS7104 and DXS418. The physical length of this region is ∼6 Mb. Mutations in the GRPR gene and M6b genes were excluded by sequence analysis. Nearby genes in which mutations are known to be associated with mental retardation (RPS6KA3, STK9, and VCXA, B and C), were excluded by position. © 2003 Wiley‐Liss, Inc.
Prenatal diagnosis of mosaic tetrasomy 10p associated with megacisterna magna, echogenic focus of left ventricle, umbilical cord cysts and distal arthrogryposis
Authors: Wu Yi‐Cheng , Yu Ming‐Tsung , Chen Ling‐Chao , Chen Cheng‐Li , Yang Man‐Li
Published: February 2003

We present the first report of mosaic isochromosome 10p associated with multiple congenital anomalies including megacisterna magna, echogenic focus of the left ventricle, umbilical cord cysts, and distal arthrogryposis. The most obvious anomalies found on prenatal ultrasound were enlarged cisterna magna and lower limb flexion contractures which resembled clubfeet. Analyses of GTG‐banded chromosomes of 42 cells harvested from 32 independent tissue culture colonies were examined. Thirty‐five cells from 27 colonies had 46 chromosomes and appeared to be 46,XX, female karyotype. Seven cells from independent colonies had 47 chromosomes with abnormal karyotypes. The extra chromosome material was identified as isochromosome 10p without involvement of the heterochromatic region of the long arm [47,XX,+ i(10p)]. Mosaic tetrasomy 10p was confirmed using fluorescent in situ hybridization (FISH) of a 10p‐specific probe to metaphase chromosomes of this patient. © 2003 Wiley‐Liss, Inc.
Novel perforin mutation in a patient with hemophagocytic lymphohistiocytosis and CD45 abnormal splicing
Authors: McCormick James , Flower Darren R. , Strobel Stephan , Wallace Diana L. , Beverley Peter C.L. , Tchilian Elma Z.
Published: February 2003

Hemophagocytic lymphohistiocytosis (HLH) composes a group of rare heterogenous disorders characterized by uncontrolled accumulation and infiltration of activated T lymphocytes and macrophages. Cytotoxic T and natural killer cell activity is significantly reduced or absent in these patients. Mutations in the important mediator of lymphocyte cytotoxicity perforin were identified in a number of HLH individuals. Here we report a novel missense mutation thr435met in the conserved Ca2+ binding domain of perforin in a patient with HLH. Prediction of the 3‐dimensional structure of the thr435met perforin mutant using comparative molecular modeling indicates that the protein's ability to bind Ca2+, and therefore its cytolytic function, would be strongly compromised. In addition, this patient exhibited abnormal CD45 splicing caused by a C77G mutation in the gene encoding CD45 (PTPRC). Our findings suggest a combined role for perforin mutation and abnormal CD45 splicing as significant contributory factors in the pathogenesis of HLH. © 2003 Wiley‐Liss, Inc.
Familial MCA/MR syndrome due to inherited submicroscopic translocation t(18;21)(q22.1q21.3) with breakpoint at the Down syndrome critical region
Authors: Horn Denise , Neitzel Heidemarie , Tönnies Holger , Kalscheuer Vera , Kunze Jürgen , Hinkel Georg Klaus , Bartsch Oliver
Published: February 2003

We report three generation family that includes two patients with severe mental retardation and additional anomalies who have been studied, clinically, cytogenetically, and molecular cytogenetically. A clinical diagnosis could not be made in the propositus, but facial anomalies of Down syndrome (DS) were recognized in the maternal uncle of the propositus. In view of a strong family history of recurrent miscarriage, a familial translocation was highly suggestive. Standard cytogenetic analysis did not reveal any abnormalities. Fluorescence in situ hybridization (FISH) using subtelomeric DNA probes identified a familial cryptic translocation of chromosomes 18 and 21, resulting in partial trisomy 21 and partial monosomy 18q in both patients. FISH analysis of obligate carriers demonstrated a balanced translocation between the terminal parts of 18q and 21q. Including this family, a total of six different familial cases with cryptic or subtle subtelomeric translocations of chromosome 21q has been reported, of which three involved terminal parts of chromosome 18q. The remarkable similarity of the chromosomal breakpoints of our patients and the described families prompted us to refine the breakpoints and to discuss phenotypic differences between these patients. Our results reinforce the role of cryptic subtelomeric rearrangements in patients with mental retardation associated with physical anomalies and stress the importance of FISH technology to supplement routine cytogenetics. © 2003 Wiley‐Liss, Inc.
FISH and cytogenetic characterization of a terminal chromosome 1q deletion: Clinical case report and phenotypic implications
Authors: Gentile M. , Di Carlo A. , Volpe P. , Pansini A. , Nanna P. , Valenzano M.C. , Buonadonna A.L.
Published: February 2003

We report a 24‐year‐old woman with minor facial anomalies, mental retardation, seizures, and partial agenesis of the corpus callosum. Cytogenetic analysis showed a de novo terminal chromosome 1 long arm deletion. FISH with a panel of chromosome 1q42‐qter bands‐specific BAC and YAC clones located the breakpoint at the 1q42‐q43 junction, with monosomy restricted to the 1q43 and 1q44 bands. The changing craniofacial phenotype of this patient with age is described as part of the del(1)(q) syndrome natural history. The patient's features are compared with those of other patients with similar deletions, and variable phenotypic findings due to different deleted chromosomal segments are discussed. © 2003 Wiley‐Liss, Inc.
Prenatal diagnosis of isolated femoral bent bone skeletal dysplasia: Problems in differential diagnosis and genetic counseling
Authors: Pryde Peter G. , Zelop C. , Pauli R.M.
Published: February 2003

Severe localized and symmetric bowing of the femora, in the absence of other significant skeletal or nonskeletal abnormalities, is a rare prenatal ultrasound finding. A 38‐year‐old woman was referred at 19 weeks gestation and ultrasound of the fetus showed severe shortening, and marked symmetric bowing of the femora. A provisional diagnosis of kyphomelic dysplasia (KD) was made. The patient elected termination of pregnancy and post mortem assessments were most consistent with kyphomelic dysplasia. KD is bent‐bone skeletal dysplasia that, in contrast to campomelic dysplasia, involves principally the femora with relative sparing of the remainder of the skeleton. KD can be difficult to distinguish, particularly from symmetric cases of femoral hypoplasia unusual facies syndrome (FH‐UFS), and few prenatal diagnoses have been reported. Because KD is thought to an be autosomal recessive disorder, the possibility that definitive diagnosis may not be possible prenatally, and even by postmortem assessment in cases choosing to abort, is an important counseling consideration. © 2003 Wiley‐Liss, Inc.
Ring chromosome 12 with variable phenotypic features: Clinical report and review of the literature
Authors: Parmar Ramesh C. , Muranjan Mamta N. , Kotvaliwale S. , Sharma Seema , Bharucha B.A.
Published: February 2003

A ring chromosome 12 (p13; q24.33) was observed in all cells analyzed from peripheral blood lymphocytes of a 15‐year‐old female referred for academic difficulties and growth delay. In addition to clinical manifestations generally observed with ring chromosome 12 such as growth retardation, mental deficiency, microcephaly, the patient had bilateral pseudocamptodactyly of little fingers, mild hirsutism, exaggerated lumbar lordosis, and ostium secundum atrial septal defect (ASD). The clinical features of reported cases are analyzed. The only consistent features were growth retardation and mental deficiency. Breakpoint in all the cases has been at the telomeric region with minimal deletion of chromosomal material. An account of complex changes at mitosis and meiosis in ring chromosome has been given. Examination of 200 metaphases demonstrated 2% cell line was showing 45,XX, ‐12. Serum lactate dehydrogenase (LDH) level was normal ruling out overlapping monosomy 12 syndrome. © 2003 Wiley‐Liss, Inc.
A Series of supernumerary small ring marker autosomes identified by FISH with chromosome probe arrays and literature review excluding chromosome 15
Authors: Daniel Art , Malafiej Paul
Published: February 2003

Seven supernumerary small ring marker autosomes were studied. The pantelomere probe (Oncor) in conjunction with scoring for dicentric rings was used to confirm ring morphology. The small rings were identified mainly by FISH with chromosome probe arrays (Cytocell) containing representations from all 24 chromosomes and the rings were derived from chromosomes 7, 8 (three cases), 11, 12, and 14. The effectiveness of the array methodology in identifying markers was tested. Microsatellite DNA data showed biparental disomy (BPD) was present for the rings from chromosomes 7 and 14 thereby excluding UPD, both were de novo but the ring 14 was of paternal origin. The literature on supernumerary small ring autosomes was reviewed excluding chromosome 15. The grade and distribution of mosaicism was invoked as the major determinant of the differences in phenotype and, in addition, variation was attributed to the possibility of different contributions from each chromosome arm. There are 88 published supernumerary small ring cases in total, with phenotypic data attributable to the respective rings in 77 cases and all chromosomes being represented except chromosome 17. Of the prenatally ascertained cases, where there was adequate phenotypic data, 30% had an abnormal phenotype attributable to the ring, and there were 44% familial cases in this group. Of the postnatally ascertained small rings, 75% had an abnormal phenotype attributable to the ring and there were 13% familial cases. This higher abnormality rate is concordant with the considerable ascertainment bias of this latter group and the prenatal data are recommended for genetic counseling. Although data are small there were some differences between the rings derived from different chromosomes. Chromosomes 3 and 8 demonstrate the extremes. Of the supernumerary small r(8) cases reviewed including the three presently described, 8/11 had an abnormal phenotype attributable to the marker but of the small r(3) cases, only 1/6 had an abnormal phenotype. Two of the present r(8) were studied with the GATA4 probe at 8p23.1. The r(8) in case 2 (patient moderately retarded) was comprised mostly of an intact 8p whereas the larger r(8) in case 3 (normal phenotype) was missing 8p23.1 → pter and had more of 8q contributing to the ring. In other supernumerary rings postnatally ascertained, there is mostly insufficient data but there is an abnormal phenotype in 8/11 cases with multiple small rings, in 5/6 cases with r(20), and in 5/10 with r(1). A novel origin for supernumerary small rings is proposed: that they may originate from incompletely digested superfluous (haploid) pronuclei. The small rings presumptively so formed may occasionally be transfected into the zygote nucleus. The high proportion (∼12.5%) of cases with multiple supernumerary small rings almost always of different centromeric origin is consistent with this concept. © 2003 Wiley‐Liss, Inc.
Submicroscopic terminal deletion of 1p36.3 and Xp23 hidden in complex chromosome rearrangements: Independent mechanism of telomere restitution on the two chromatids
Authors: Reddy Kavita S. , Yang Xiaojing
Published: February 2003

In this study, we report two cases each with a complex chromosome rearrangement concealing a submicroscopic terminal deletion. The first case had a mos 46,XX,der(1)t(1;9)(p36.3;p13). ish der(1)(wcp9 +, 1ptel−, 9ptel +, pan tel +)[88]/46,XX. ish del(1)(1ptel −, 9ptel −, pan tel +)[12] karyotype. Scrutiny by FISH using wcp 9, 1ptel, 9ptel, and pan telomeric probes found a subtelomeric 1ptel deletion on the der(1) in the abnormal cell line and on a chromosome 1 in the apparently normal cell line. The telomere (TTAGGG)n, however, was present on the terminal ends of both copies of chromosome 1 in the apparently normal and abnormal cell lines. The second case had a de novo mos 46,X,der(X)t(X;22)(p22.3;q11.2),inv dup(22)(q11.2).ish der(X)(wcpX +,wcp22 +,KAL +, STS −,Xptel −,BCR +),inv dup(22)(wcp22 +,TUPLE ++,BCR −)[85]/45,X,der(X)t(X;22)(p22.3;q11.2),− 22[15].ish der(X)(wcpX +,wcp22 +, KAL +,STS −,Xptel −,BCR +) karyotype. FISH probes identified a terminal Xpter deletion, distal to the KAL gene. The two rearrangements are hypothesized to have been initiated by a terminal deletion. We propose a model for the formation of the rearrangement in Case 1, which invokes independent telomere stabilization of the sister chromatids. A terminal deletion 1pter in meiosis, was followed by acquiring or regenerating a telomere (TTAGGG)n cap on one chromatid and the other chromatid was involved in a translocation with a chromosome 9 chromatid. Following segregation of this chromosome the viable cell line survives to form the mosaic karyotype. Our findings suggest that subtelomeric deletions should be ruled out in cases with complex and simple rearrangements involving the terminal regions. © 2003 Wiley‐Liss, Inc.
De novo double translocation 3;13 and 4;8;18 in a patient with mental retardation and skeletal abnormalities
Authors: Battisti C. , Bonaglia M.C. , Giglio S. , Anichini C. , Pucci L. , Dotti M.T. , Zuffardi O. , Federico A.
Published: February 2003

A de novo, apparently balanced complex chromosome rearrangement (CCR) involving five chromosomes and six chromosome breakpoints was found in a child with Marfanoid habitus, kyphoscoliosis, axillary pterygium, camptodactyly, joint laxity, and mild mental retardation. Fluorescence in situ hybridization (FISH) revealed a simple translocation involving chromosomes 3 and 13, and a complex rearrangement involving chromosomes 4, 8, and 18 with four breakpoints. © 2003 Wiley‐Liss, Inc.
Zimmermann–Laband syndrome associated with a balanced reciprocal translocation t(3;8)(p21.2;q24.3) in mother and daughter: Molecular cytogenetic characterization of the breakpoint regions
Authors: Stefanova Margarita , Atanassov Dimitar , Krastev Tzaniu , Fuchs Sigrid , Kutsche Kerstin
Published: February 2003

Zimmermann–Laband syndrome (ZLS) is a rare disorder characterized by gingival fibromatosis, abnormalities of the nose and/or ears, and absence or hypoplasia of nails or terminal phalanges of hands and feet. Other more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism, and mental retardation. The genetic basis of ZLS is unknown; autosomal dominant inheritance has been suggested. We report an apparently balanced chromosomal aberration, 46,XX, t(3;8)(p13‐p21.2;q24.1‐q24.3), in a family with an affected mother and daughter. Using fluorescence in situ hybridization with BAC clones, we refined the breakpoints to 3p21.2 and 8q24.3 and, thereby, narrowed down both breakpoint regions to approximately 1.5 Mb. Our data provide additional support to the assumption that ZLS follows autosomal dominant inheritance. The 3;8 translocation described here represents a powerful resource to identify the causative gene for ZLS that maps most likely to one of the breakpoints. © 2003 Wiley‐Liss, Inc.
Waardenburg syndrome: Clinical differentiation between types I and II
Authors: Pardono Eliete , van Bever Yolande , van den Ende Jenneke , Havrenne Poti C. , Iughetti Paula , Maestrelli Sylvia R.P. , Costa F Orozimbo , Richieri‐Costa Antonio , Frota‐Pessoa Oswaldo , Otto Paulo A.
Published: February 2003

Here we present the results of a study performed on 59 patients affected by Waardenburg syndrome (WS), 30 with the I variant, 21 having the type II, and 8 of them being isolated cases without telecanthus. These patients belong to 37 families; the main contributions and conclusions are based on the detailed study of 25 of these families, examined using standard procedures. All patients were examined as to the presence of eight cardinal signs important for the diagnosis of the condition; from each patient, from many of his/her normal relatives, and from a control sample of 300 normal individuals stratified by age and sex, 23 different craniofacial measurements were obtained. We also estimated, using our own data as well those collected from the literature, the frequencies of the cardinal signs, based on a total sample of 461 affected individuals with WSI and 121 with WSII. In order to originate discriminant functions to separate individuals affected by one of the two variants, both metric (from craniofacial measurements) as well as categoric data (based on the frequencies of the cardinal signs or symptoms) were used. Discriminant analysis based on the frequency of the eight cardinal signs can improve the separation of WSI patients without telecanthus from those presenting the variant II. We present also a Table with the conditional probabilities favoring the diagnosis of WSI for suspect subjects without telecanthus and any combination of the other seven signs/symptoms. The discriminant function based on the four ocular measurements (inner and outer intercanthal, interpupillary, and inferior lacrymal distances), on the other side, perfectly classifies patients affected by one of the variants of WS, the same taking place when the average values of the W index of all affected individuals per family are used. The discriminant function based solely in the individual W index values of patients correctly classifies 93% of WSII subjects, but only 60% of the patients with the I variant of WS. © 2003 Wiley‐Liss, Inc.
Two unique patients with trisomy 18 mosaicism and molecular marker studies
Authors: Slavotinek A. , Poyser L. , Wallace A. , Martin F. , Gaunt L. , Kingston H.
Published: February 2003

We report two unusual patients with trisomy 18 mosaicism presenting with minor anomalies and failure to thrive in the first year of life. Chromosome analysis showed trisomy 18 in 30/30 peripheral blood lymphocytes in both children. Analysis of skin fibroblasts in the first child showed normal female chromosomes in 30/30 cells, and the fibroblast karyotype in the second child showed mosaicism for tetrasomy 18p, trisomy 18, and normal female chromosomes (karyotype 47,XX, +i(18)(p10)[47]/47,XX, +18[9] /46,XX[4]). Trisomy 18 commonly results from nondisjunction at maternal meiosis II (MII). Nondisjunction at maternal MII has also been postulated to be the initial step in the formation of tetrasomy 18p. In our second case, the additional chromosome 18 was the result of maternal nondisjunction at MII, consistent with this hypothesis. In the first case, nondisjunction at maternal meiosis I (MI) was responsible for the extra chromosome 18. © 2002 Wiley‐Liss, Inc.
Sudden infant death syndrome: Association with a promoter polymorphism of the serotonin transporter gene
Authors: Weese‐Mayer Debra E. , Berry‐Kravis Elizabeth M. , Maher Brion S. , Silvestri Jean M. , Curran Mark E. , Marazita Mary L.
Published: February 2003

Serotonergic receptor binding in the arcuate nucleus, n. raphé obscurus, and other medullary regions is decreased in sudden infant death syndrome (SIDS) cases. Further, a variable tandem repeat sequence polymorphism in the promoter region of the serotonin transporter protein (5‐HTT) gene has recently been associated with risk of SIDS in a Japanese cohort. This polymorphism differentially regulates 5‐HTT expression, with the long allele (L), the SIDS‐associated allele, being a more effective promoter than the short allele (S). We therefore investigated the 5‐HTT promoter polymorphism in a cohort of 87 SIDS cases (43 African American and 44 Caucasian) and gender/ethnicity‐matched controls. Significant positive associations were found between SIDS and the 5‐HTT genotype distribution (P = 0.022), specifically with the L/L genotype (P = 0.048), and between SIDS and the 5‐HTT L allele (P = 0.005). There was also a significant negative association between SIDS and the S/S genotype (P = 0.011). The comparisons were repeated in the African American and Caucasian subgroups. The data patterns were consistent in the subgroups, i.e., the L/L genotype and L allele were increased in the cases, but not all subgroup comparisons were statistically significant. These results indicate a relationship between SIDS and the L allele of the 5‐HTT gene in African Americans and Caucasians, and if confirmed, will provide an important tool for identifying at‐risk individuals and estimating the risk of recurrence. © 2003 Wiley‐Liss, Inc.
Neurotrophic cross‐talk between the nervous and immune systems: Implications for neurological diseases
Authors: Kerschensteiner Martin , Stadelmann Christine , Dechant Georg , Wekerle Hartmut , Hohlfeld Reinhard
Published: February 2003

Inflammatory reactions in the central nervous system usually are considered detrimental, but recent evidence suggests that they also can be beneficial and even have neuroprotective effects. Intriguingly, immune cells can produce various neurotrophic factors of various molecular families. The concept of “neuroprotective immunity” will have profound consequences for the pathogenesis and treatment of neuroinflammatory diseases such as multiple sclerosis. It also will prove important for neurodegenerative disorders, in which inflammatory reactions often occur. This review focuses on recent findings that immune cells produce brain‐derived neurotrophic factor in multiple sclerosis lesions, whereas neurons and astrocytes express the appropriate tyrosine kinase receptor TrkB. Together with functional evidence for the neuroprotective effects of immune cells, these observations support the concept of “neuroprotective immunity.” We next examine current and future therapeutic strategies for multiple sclerosis and experimental autoimmune encephalomyelitis in light of neuroprotective immunity and finally address the broader implications of this new concept for other neuroinflammatory and neurodegenerative diseases. Ann Neurol 2003
Mechanisms underlying cerebellar motor deficits due to mGluR1‐autoantibodies
Authors: Coesmans Michiel , Sillevis Smitt Peter A. , Linden David J. , Shigemoto Ryuichi , Hirano Tomoo , Yamakawa Yoshinori , Van Alphen Adriaan M. , Luo Chongde , Van Der Geest Josef N. , Kros Johan M. , Gaillard Carlo A. , Frens Maarten A. , De Zeeuw Chris I.
Published: February 2003

Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1‐Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1‐Abs block induction of long‐term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects. Ann Neurol 2003;53:000–000
Chronic hydrocephalus in rats and humans: White matter loss and behavior changes
Authors: Del Bigio Marc R. , Wilson Marla J. , Enno Terry
Published: February 2003

Chronic hydrocephalus that begins in childhood and progresses only very gradually is sometimes called “arrested” hydrocephalus. Data suggest that this state eventually can become symptomatic and may be treatable by shunting. However, the pathological substrate of the disorder is not entirely understood. We studied chronic hydrocephalus in rats, 9 months after induction by kaolin injection into the cisterna magna, and in humans. In both circumstances, destruction of periventricular white matter structures was worst in those with the largest ventricles. Structures damaged include the corpus callosum, corticospinal tract, and fimbria/fornix projections from the hippocampus. Myelin turnover was increased. These changes were associated with deficits of motor and cognitive function. The cerebral cortex was largely spared. There appears to be a threshold of ventricle size beyond which functional changes manifest, but this undoubtedly is modified by factors such as age of onset and rate of enlargement. These data support the need for persistent follow‐up of patients with chronic, apparently stable hydrocephalus. A slight increase in size of already enlarged ventricles might cause significant axonal damage.
Autoantigen diversity in the opsoclonus‐myoclonus syndrome
Authors: Bataller Luis , Rosenfeld Myrna R. , Graus Francesc , Vilchez Juan J. , Cheung Nai‐Kong V. , Dalmau Josep
Published: February 2003

Despite circumstantial evidence that opsoclonus‐myoclonus (OM) is often immune mediated, no specific autoantigen has been identified. Using sera of 21 patients with several types of OM (idiopathic, associated to small cell lung cancer, and associated to neuroblastoma), we probed a brainstem cDNA library to isolate target neuronal antigens. Thirty‐seven clones coding for 25 proteins were isolated, with two groups of autoantigens emerging: (1) proteins of the postsynaptic density, among them the adenomatous polyposis coli, and 2) proteins with expression or function restricted to neurons, including RNA or DNA‐binding proteins and zinc‐finger proteins. Usually, each patient's serum recognized a different autoantigen, except for adenomatous polyposis coli that was recognized by sera of two patients with idiopathic OM and two control patients with nystagmus, diplopia, and paraneoplastic brainstem dysfunction. Overall, in the indicated types of OM, (1) we found frequent and heterogeneous immunity to neuronal autoantigens without a single specific antibody marker of OM, (2) the occasional detection of antibodies to known onconeuronal antigens (ie, Hu proteins) probably is related to cancer‐induced immunity rather than to OM, and (3) the postsynaptic density is a frequent source of novel autoantigens, with several proteins of this complex targeted by antibodies of OM patients. Ann Neurol 2003
Progressive neocortical damage in epilepsy
Authors: Liu Rebecca S. N. , Lemieux Louis , Bell Gail S. , Hammers Alexander , Sisodiya Sanjay M. , Bartlett Philippa A. , Shorvon Simon D. , Sander Josemir W. A. S. , Duncan John S.
Published: February 2003

Our objective was to determine the pattern and extent of generalized and focal neocortical atrophy that develops in patients with epilepsy and the factors associated with such changes. As part of a prospective, longitudinal follow‐up study of 122 patients with chronic epilepsy, 68 newly diagnosed patients, and 90 controls, serial magnetic resonance imaging scans were obtained 3.5 years apart. Image subtraction was used to identify diffuse and focal neocortical change that was quantified with a regional brain atlas and a fully automated segmentation algorithm. New focal or generalized neocortical volume losses were identified in 54% of patients with chronic epilepsy, 39% of newly diagnosed patients and 24% of controls. Patients with chronic epilepsy were significantly more likely to develop neocortical atrophy than control subjects. The increased risk of cerebral atrophy in epilepsy was not related to a history of documented seizures. Risk factors for neocortical atrophy were age and multiple antiepileptic drug exposure. Focal and generalized neocortical atrophy commonly develops in chronic epilepsy. Neocortical changes seen in a quarter of our control group over 3.5 years were likely to reflect physiological changes. Our results show that ongoing cerebral atrophy may be widespread and remote from the putative epileptic focus, possibly reflecting extensive networks and interconnections between cortical regions. Ann Neurol 2003
Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23
Authors: Marconi Roberto , De Fusco Maurizio , Aridon Paolo , Plewnia Katrin , Rossi Maja , Carapelli Sadia , Ballabio Andrea , Morgante Letterio , Musolino Rosa , Epifanio Antonio , Micieli Giuseppe , De Michele Giuseppe , Casari Giorgio
Published: February 2003

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder characterized by episodes of transient hemiparesis followed by headache. Two chromosomal loci are associated to FHM: FHM1 on chromosome 19 and FHM2 on chromosome 1q21‐23. Mutations of the α‐1A subunit of the voltage gated calcium channel (CACNA1A) are responsible for FHM1. FHM2 critical region spans 28cM, hence hampering the identification of the responsible gene. Here, we report the FHM2 locus refining by linkage analysis on two large Italian families affected by pure FHM. The new critical region covers a small area of 0.9Mb in 1q23 and renders feasible a positional candidate approach. By mutation analysis, we excluded the calsequestrin and two potassium channel genes mapping within the narrowed FHM2 locus. Ann Neurol 2003
μ Opioid receptors and analgesia at the site of a peripheral nerve injury
Authors: Truong Wayne , Cheng Chu , Xu Qing‐Gui , Li Xia‐Qing , Zochodne Douglas W.
Published: February 2003

Opioid ligands may exert antinociception through receptors expressed on peripheral afferent axons. Whether local opioid receptors might attenuate neuropathic pain is uncertain. In this work, we examined the function and expression of local μ opioid receptors (MORs) associated with the chronic constriction injury (CCI) model of sciatic neuropathic pain in rats. Low‐dose morphine or its carrier were percutaneously superfused over the CCI site with the injector blinded to the identity of the injectate. Morphine, but not its carrier, and not equimolar systemic doses of morphine reversed thermal hyperalgesia in a dose‐related, naloxone‐sensitive fashion. Moreover, analgesia was conferred at both 48 hours and 14 days after CCI, times associated with very different stages of nerve repair. Equimolar local DAGO ([D‐Ala2, N‐Me‐Phe4, Gly5‐(ol)] enkephalin), a selective MOR ligand, provided similar analgesia. Local morphine also attenuated mechanical allodynia. MOR protein was expressed in axonal endbulbs of Cajal just proximal to the injury site, in aberrantly regenerating small axons in the epineurial sheath around the CCI site and in residual small axons distal to the CCI lesion. Sensory neurons ipsilateral to CCI had an increase in the proportion of neurons expressing MOR. We suggest that local MOR expressed in axons may be exploited to modulate some forms of neuropathic pain. Ann Neurol 2003
Schwann cell expression of PLP1 but not DM20 is necessary to prevent neuropathy
Authors: Shy Michael E. , Hobson Grace , Jain Manisha , Boespflug‐Tanguy Odile , Garbern James , Sperle Karen , Li Wen , Gow Alex , Rodriguez Diana , Bertini Enrico , Mancias Pedro , Krajewski Karen , Lewis Richard , Kamholz John
Published: February 2003

Proteolipid protein (PLP1) and its alternatively spliced isoform, DM20, are the major myelin proteins in the CNS, but are also expressed in the PNS. The proteins have an identical sequence except for 35 amino acids in PLP1 (the PLP1‐specific domain) not present in DM20. Mutations of PLP1/DM20 cause Pelizaeus‐Merzbacher Disease (PMD), a leukodystrophy, and in some instances, a peripheral neuropathy. To identify which mutations cause neuropathy, we have evaluated a cohort of patients with PMD and PLP1 mutations for the presence of neuropathy. As shown previously, all patients with PLP1 null mutations had peripheral neuropathy. We also identified 4 new PLP1 point mutations that cause both PMD and peripheral neuropathy, three of which truncate PLP1 expression within the PLP1‐specific domain, but do not alter DM20. The fourth, a splicing mutation, alters both PLP1 and DM20, and is probably a null mutation. Six PLP1 point mutations predicted to produce proteins with an intact PLP1‐specific domain do not cause peripheral neuropathy. Sixty‐one individuals with PLP1 duplications also had normal peripheral nerve function. These data demonstrate that expression of PLP1 but not DMSO is necessary to prevent neuropathy, and suggest that the 35 amino acid PLP1‐specific domain plays an important role in normal peripheral nerve function. Ann Neurol 2003
Epileptiform ictal discharges are prevented by periodic interictal spiking in the olfactory cortex
Authors: Librizzi Laura , de Curtis Marco
Published: February 2003

Interictal potentials are commonly observed between seizures in human epilepsies and in animal models of epilepsy. It is uncertain whether interictal spiking in partial epilepsies is causally related with the onset of an ictal discharge. To analyze the reciprocal correlation between interictal and ictal epileptiform events, we performed extracellular recordings in the limbic system of the in vitro isolated guinea pig brain preparation. Arterial perfusion of bicuculline (50μM) in vitro consistently induced a focal ictal discharge in the hippocampal‐entorhinal region that in one third of the experiments was associated with periodic interictal spikes in the piriform cortex. In the absence of active interictal spiking, the piriform cortex was secondarily invaded by the ictal discharge initiated in the hippocampal‐entorhinal region, whereas no secondary ictal entrainment was observed in the presence of periodic piriform cortex spikes at circa 0.1 to 0.2Hz. Similarly, ictal events never occurred when arterial perfusion of bicuculline was preceded by a local injection of the same drug in the piriform cortex, a procedure that induces a sustained interictal spiking. A reduced responsiveness to incoming paroxysmal discharges generated in the hippocampus was observed during the interval between two interictal spikes in the piriform cortex. Ann Neurol 2003
A new mutation of the fukutin gene in a non‐Japanese patient
Authors: Silan Fatma , Yoshioka Mieko , Kobayashi Kazuhiro , Simsek Enver , Tunc Murat , Alper Murat , Cam Meryem , Guven Aysel , Fukuda Yoji , Kinoshita Moritoshi , Kocabay Kenan , Toda Tatsushi
Published: February 2003

Fukuyama‐type congenital muscular dystrophy (FCMD), Walker–Warburg syndrome, and muscle‐eye‐brain disease are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, cobblestone lissencephaly, and eye anomalies. FCMD is frequent in Japan, but no FCMD patient with confirmed fukutin gene mutations has been identified in a non‐Japanese population. Here, we describe a Turkish CMD patient with severe brain and eye anomalies. Sequence analysis of the patient's DNA identified a homozygous 1bp insertion mutation in exon 5 of the fukutin gene. To our knowledge, this is the first case worldwide in which a fukutin mutation has been found outside the Japanese population. This report emphasizes the importance of considering fukutin mutations for diagnostic purposes outside of Japan. Ann Neurol 2003
Epilepsy with auditory features: A LGI1 gene mutation suggests a loss‐of‐function mechanism
Authors: Pizzuti Antonio , Flex Elisabetta , Di Bonaventura Carlo , Dottorini Tania , Egeo Gabriella , Manfredi Mario , Dallapiccola Bruno , Giallonardo Anna Teresa
Published: February 2003

Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a genetically heterogeneous disorder. Some patients exhibit mutations in the leucine‐rich glioma inactivated (LGI1) gene. In an ADPEAF family, a novel mutation in the Lgi1 signal peptide is predicted to interfere with the protein cell sorting, resulting in altered processing. This finding suggests a loss‐of‐function mechanism for LGI1 gene mutations causing ADPEAF even if other mechanisms cannot be ruled out. Ann Neurol 2003;53:396–399
CMT4A: Identification of a Hispanic GDAP1 founder mutation
Authors: Boerkoel Cornelius F. , Takashima Hiroshi , Nakagawa Masanori , Izumo Shuji , Armstrong Dawna , Butler Ian , Mancias Pedro , Papasozomenos Sozos C. H. , Stern Lawrence Z. , Lupski James R.
Published: February 2003

Mutations of the ganglioside‐induced differentiation‐associated protein 1 gene (GDAP1) cause autosomal recessive Charcot–Marie–Tooth disease type 4A. We report four additional families with recessive mutations (487C→T, Q163X; 359G→A, R120Q) of GDAP1; Q163X occurred in three unrelated Hispanic families that had the same haplotype suggesting a Spanish founder mutation. Both the Q163X and the R120Q mutation cause demyelination and axonal loss. The patients had symptoms within the first two years of life and involvement of cranial, sensory, and enteric nerves. Neuropathology showed loss of large myelinated fibers, onion bulb formations and focal folding of the outer myelin lamina. Ann Neurol 2003;53:400–405
Cerebral neurogenesis is induced by intranasal administration of growth factors
Authors: Jin Kunlin , Xie Lin , Childs Jocelyn , Sun Yunjuan , Mao Xiao Ou , Logvinova Anna , Greenberg David A.
Published: February 2003

Neurogenesis persists in the adult brain, where it may contribute to repair and recovery after injury, but the lack of methods for noninvasive stimulation of cerebral neurogenesis limits its potential for clinical application. We report that intranasal administration of either fibroblast growth factor–2 or heparin‐binding epidermal growth factor–like growth factor increases neurogenesis, measured by the incorporation of bromodeoxyuridine into cells that express the early neuronal marker protein doublecortin in the subventricular zone of mouse brain. These findings indicate that intranasal growth factors may have potential as neurogenesis‐promoting therapeutic agents. Ann Neurol 2003;53:405–409
PRNP Val129 homozygosity increases risk for early‐onset Alzheimer's disease
Authors: Dermaut Bart , Croes Esther A. , Rademakers Rosa , Van Den Broeck Marleen , Cruts Marc , Hofman Albert , Van Duijn Cornelia M. , Van Broeckhoven Christine
Published: February 2003

We analyzed the PRNP M129V polymorphism in a Dutch population‐based early‐onset Alzheimer's disease sample. We observed a significant association between early‐onset Alzheimer's disease and homozygosity of M129V (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1–3.3; p = 0.02) with the highest risk for V homozygotes (OR, 3.2; 95% CI, 1.4–7.1; p < 0.01). In patients with a positive family history, these risks increased to 2.6 (95% CI, 1.3–5.3; p < 0.01) and 3.5 (95% CI, 1.3–9.3; p = 0.01), respectively. Ann Neurol 2003;53;409–412
Seizure exacerbation associated with inhibition of progesterone metabolism
Authors: Herzog Andrew G. , Frye Cheryl A.
Published: February 2003

The reduced progesterone metabolite tetrahydroprogesterone is a potent positive modulator of GABAA chloride conductance that exerts powerful neuroinhibitiory and antiseizure effects in animal models. Cyclic natural progesterone use may lessen seizure frequency in women with catamenial seizure exacerbation. We report a case in which efficacy was eliminated during concomitant treatment with a reductase inhibitor. The observation suggests that a reduced metabolite, rather than progesterone itself, was responsible for improved seizure control. Ann Neurol 2003;53:390–391
Hippocampal sclerosis is a progressive disorder: A longitudinal volumetric MRI study
Authors: Fuerst Darren , Shah Jagdish , Shah Aashit , Watson Craig
Published: February 2003

Twelve patients with refractory temporal lobe epilepsy and unilateral hippocampal sclerosis had repeat volumetric magnetic resonance imaging scans after a mean of 3.4 years to determine whether progressive hippocampal volume loss occurred. Seizure‐free patients showed no change in hippocampal volume. Patients with continuing seizures had a decline in ipsilateral hippocampal volume that correlated with seizure frequency. Patients with medically refractory temporal lobe epilepsy and unilateral hippocampal sclerosis have progressive hippocampal atrophy. Ann Neurol 2003;53:413–416
Outcome in psychogenic nonepileptic seizures: 1 to 10‐year follow‐up in 164 patients
Authors: Reuber Markus , Pukrop Ralf , Bauer Jürgen , Helmstaedter Christoph , Tessendorf Natalie , Elger Christian Erich
Published: February 2003

Our knowledge of longer term outcome in psychogenic nonepileptic seizures (PNESs) patients is limited; we know less still about factors predicting prognosis. This study was intended to describe outcome in a large cohort and to identify predictive clinical and psychological factors to generate new ideas for treatment. One hundred sixty‐four adult patients with PNESs (66.7%) responded to outcome, personality, and psychosymptomatology questionnaires (Dimensional Assessment of Personality Pathology–Basic Questionnaire [DAPP‐BQ], Dissociative Experiences Scale, and Screening Test for Somatoform Symptoms) a mean of 11.9 years after manifestation and 4.1 years after diagnosis of PNES. Additional clinical data were retrieved from hospital records. The responses showed that 71.2% of patients continued to have seizures and 56.4% were dependent on social security. Dependence increased with follow‐up. Outcome was better in patients with greater educational attainments, younger onset and diagnosis, attacks with less dramatic features, fewer additional somatoform complaints, and lower dissociation scores. Better outcome was associated with lower scores of the higher order personality dimensions “inhibitedness,” “emotional dysregulation,” and “compulsivity” but not “dissocial behavior” (DAPP‐BQ). Outcome in PNESs is poor but variable. Clinical and personality factors can be used to provide an individualized prognosis. By generating a patient‐specific profile, they show particular maladaptive traits or tendencies that can identify goals for psychological therapy.
Free radical Co‐ and terpolymerization of styrene, hydrogenated cardanyl acrylate, and cardanyl acetate
Authors: Nguyen Le Huong , Koerner Hilmar , Lederer Klaus
Published: February 2003

Hydrogenated cardanyl acrylate (HCA) and cardanyl acetate (CACE) were synthesized from cardanol. The copolymerizations of HCA, CACE, and styrene (S) with methyl ethyl ketone peroxide (MEKP) and cobalt salt as the initiator were studied by FTIR. Based on FTIR results the reactivity ratios of the three copolymerization systems S–HCA, S–CACE, and HCA–CACE were determined by three different methods (Mayo‐Lewis, Fineman‐Ross, and Kelen‐Tüdos). Results obtained from the three methods are in good agreement. Instantaneous compositions and composition shift as a function of conversion is calculated for the S–HCA–CACE system with different feed compositions. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1399–1409, 2003
Analysis of water trees in power cable polymeric insulation
Authors: Shuvalov M. , Mavrin M. , Ovsienko V. , Romashkin A.
Published: February 2003

This article deals with the basic mechanism of aging, that is water treeing (WT), that takes place in polymer‐insulated power cables. WT was studied by means of computer‐aided video‐enhanced microscopy, microspectrophotometry, and micromanipulation. The microdiagnostics procedure was used for cables operating in a wet environment. A phenomenological WT model aimed at estimating the residual lifetime, which considers WT as a diffusion‐with‐reaction process, was developed. The theoretical calculations were in reasonable agreement with the experimental data. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1543–1549, 2003
Curing reaction of molybdenum–phenolic resins
Authors: Hua Youqing , Zhang Zhengxi , Qin Qian
Published: February 2003

The curing behavior and curing reaction kinetics of novel molybdenum–phenolic resins were studied with differential scanning calorimetry and thermogravimetry methods, the thermal degradation properties of the cured products were studied with thermogravimetry, and the mechanism of the curing reaction was investigated with Fourier transform infrared. When the mixing ratio of the molybdenum–phenolic resin (with 12% molybdenum) to the curing agent was 100/10 (w/w), the curing temperature and activation energy were at a minimum, the thermal degradation stability of the cured product was optimal, and the temperature corresponding to the maximum extent of curing was 200°C. The curing mechanism was similar to that of conventional phenolic systems. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1410–1415, 2003
High polarization levels in poly(vinylidene fluoride–trifluoroethylene) ferroelectric thin films doped with diethyl phthalate
Authors: Xu Haisheng , Ni Suolong , Yang Changzheng
Published: February 2003

With a spin‐coating technique, ferroelectric thin films of poly(vinylidene fluoride–trifluoroethylene) copolymer [P(VDF–TrFE; with a content (mol %) ratio of 68/32 vinylidene fluoride/trifluoroethylene] were fabricated on silicon wafers covered with platinum and were doped with a nucleation agent, diethyl phthalate (DEP). The remnant polarization of copolymer thin films increased 70% after doping with DEP, and the coercive field was reduced, which is highly desirable in bistable memory devices. The dielectric constant of thin films also increased after doping. However, the effect of doping on the ferroelectric response was not remarkable in freestanding copolymer films. The results demonstrated that the ferroelectric dipole orientation in P(VDF–TrFE) thin films was significantly enhanced by the presence of DEP because the crystallinity of thin films decreased after doping, as revealed by X‐ray results. The dopant DEP acted as both a nucleation agent during the crystallization process and a plasticizer in the noncrystalline regions, which greatly enhanced the dipole orientation. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1416–1419, 2003
Synthesis and properties of graft oxidation starch sizing agent
Authors: Zhang Xiaodong , Li Wenying Liuxin
Published: February 2003

In this article, a graft, oxidation starch sizing agent was synthesized and its structure and surface morphology were analyzed by infrared (IR) spectroscopy and scanning electron microscopy (SEM). The results show that the synthesized graft oxidation starch has good gelatinizing ability, good film properties, good desizing ability, and lower hygroscopic properties. The sized yarns (T/C65/35, 13.5tex), sized with graft oxidation starch and emulsive copolymer size EM, exhibit good tensile strength and elongation at break, good abrasion resistance, and lower counts of fluff when poly (vinyl alcohol) (PVA) is substituted by ≤ 80% with graft oxidation starch. © 2003 Wiley Periodicals, Inc. J Appl Polym Sci 88: 1563–1566, 2003