bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractHere 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

AbstractWe 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

AbstractSerotonergic 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

AbstractInflammatory 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

AbstractPatients 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

AbstractChronic 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

AbstractDespite 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

AbstractOur 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

AbstractFamilial 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

AbstractOpioid 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

AbstractProteolipid 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

AbstractInterictal 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

AbstractFukuyama‐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

AbstractAutosomal 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

AbstractMutations 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

AbstractNeurogenesis 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

AbstractWe 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