bluuebunny/crossref_metadata_2025_split huggingface dataset:
GTP‐cyclohydrolase I gene mutations in hereditary progressive and dopa‐responsive dystonia
Authors: Furukawa Yoshiaki , Shimadzu Mitsunobu , Rajput Ali H. , Shimuzu Yumiko , Tagawa Tetsuzo , Mori Hideo , Yokochi Masayuki , Narabayashi Hirotaro , Hornykiewicz Oleh , Mizuno Yoshikuni , Kish Stephen J. 
Published: January 2005

AbstractRecently, mutations of the GTP‐cyclohydrolase I (GTP‐CH I) gene, which catalyzes the first step in the tetrahydrobiopterin (BH4) biosynthesis, were discovered in Japanese patients with hereditary progressive dystonial/dopa‐responsive dystonia (HPD/DRD). However, it has not been confirmed that non‐Japanese patients also contain mutations in the same gene, or whether these mutations are specific to HPD/DRD. In this study, two novel nonsense mutations in exon 1 of the GTP‐CH I gene and a new mutation at the splice acceptor site of intron 1 were identified in an autopsied case of English‐Irish descent and 2 Japanese patients with HPD/DRD. In the latter, cerebrospinal fluid (CSF) neopterin levels (which may reflect the GTP‐CH I activity in the brain) were reduced to 18% and 37% of controls. A therapeutic trial of oral BH4 was ineffective, however, in a genetically proven patient. In contrast, no mutations in any exons of the GTP‐CH I gene were found in 2 patients with early‐onset parkinsonism with dystonia (EOP‐D) who developed dopa‐responsive parkinsonism and dystonia at 6 and 8 years old, respectively. Neopterin levels in CSF were well preserved in 6 EOP‐D patients. These data suggest that, among patients of different racial backgrounds, the pathogenesis of HPD/DRD, unlike EOP‐D, involves partial reduction of the brain GTP‐CH I activity consequent to mutations in the GTP‐CH I gene. Measurement of CSF neopterin concentration may be useful for the differential diagnosis between HPD/DRD and EOP‐D.
Immune attack on the schwann cell surface in acute inflammatory demyelinating polyneuropathy
Authors: Hafer‐Macko C. E. , Sheikh K. A. , Li C. Y. , Ho T. W. , Cornblath D. R. , McKhann G. M. , Asbury A. K. , Griffin J. W. 
Published: January 2005

AbstractThe localization, mode of action, and roles of complement in the Guillain‐Barré syndrome have been controversial. We used high‐resolution immunocytochemistry to localize complement activation products in early stages of the acute inflammatory demyelinating polyneuropathy (AIDP) pattern of Guillain‐Barré syndrome. Three AIDP subjects who were autopsied had had symptoms for 3 to 9 days at the time of death. Immunocytochemistry was performed on etched, epoxy resin‐embedded sections, and the next thin section was compared by electron microscopy (thick/thin sections). Many fibers had a rim of the complement activation marker C3d and the terminal complement complex neoantigen C5b‐9 along the outer surface of the Schwann cells. Ultrastructural analysis of these C3d‐positive fibers showed mild vesicular changes of the outermost myelin lamellae. Vesicular degeneration was seen before the invasion of macrophages into the myelin, and was the predominant change in the subject with symptoms for 3 days. C3d staining was not found on myelin membranes. The results suggest that at least some forms of AIDP are complement mediated. We speculate that complement is activated by antibody bound to epitopes on the outer surface of the Schwann cell and that the resulting complement activation initiates the vesiculation of myelin.
A newly recognized autosomal dominant limb girdle muscular dystrophy with cardiac involvement
Authors: van der Kooi A. J. , Ledderhof T. M. , DeVoogt W. G. , Res J. C. J. , Bouwsma G. , Troost D. , Busch H. F. M. , Becker A. E. , DeVisser M. 
Published: January 2005

AbstractSixty‐five members of three families with limb girdle muscular dystrophy (LGMD) underwent neurological, cardiological, and ancillary investigations. Thirty‐five individuals were diagnosed as having slowly progressive autosomal dominant LGMD. Symmetrical weakness started in the proximal lower limb muscles, and gradually upper limb muscles also became affected. Early contractures of the spine were absent. Contractures of elbows and Achilles tendons were either minimal or late. Serum creatine kinase activity was normal to moderately elevated. Electromyogram and muscle biopsy were consistent with a mild muscular dystrophy. Cardiological abnormalities, found in more than one‐half the patients, included dysrhythmias and atrioventricular (AV) conduction disturbances presenting as bradycardia, syncopal attacks necessitating pacemaker implantation, and sudden cardiac death. There was a significant relation between the severity of AV conduction disturbances and age. In nearly all patients, neuromuscular symptomatology preceded cardiological involvement. The early recognition of this previously not described, autosomal dominant LGMD with life‐threatening cardiac involvement offers an opportunity for therapeutic intervention.
Acute paresis of extraocular muscles associated with IgG Anti‐GQ1b antibody
Authors: Yuki Nobuhiro 
Published: January 2005

AbstractThere have been several case reports of acute ophthalmoparesis without ataxia subsequent to infection or immunization. The nosological position and therapy for acute ophthalmoparesis have yet to be established. Sera from patients are reported to have IgG anti‐GQ1b antibody, which is frequently found in sera from patients with Fisher's syndrome. To establish the etiology of acute ophthalmoparesis, I tested sera from 8 patients with acute ophthalmoparesis for anti‐GQ1b antibody. High IgG anti‐GQ1b antibody titers were present in sera from patients in the acute phase of the illness. I describe the successful treatment with plasmapheresis and intravenous immunoglobulin. Some cases of acute ophthalmoparesis following infection or immunization may be categorized as an autoimmune disease related to Fisher's syndrome.
A novel point mutation in the mcleod syndrome gene in neuroacanthocytosis
Authors: Ho M. F. , Chalmers R. M. , Davis M. B. , Harding A. E. , Monaco A. P. MD 
Published: January 2005

AbstractMcLeod syndrome is an X‐linked recessive disorder, characterized by neuromuscular and hematopoietic dysfunction. Two cases of McLeod syndrome were reported in a family with neuroacanthocytosis and, remarkably, 1 of them was female. Direct sequence analysis of the McLeod gene in 12 members of the family revealed a novel point mutation in exon 2 that creates a frameshift and results in premature termination of translation. There was marked skewing of X inactivation in the severely affected female.
Expression of Hel‐N1 and HeL‐N2 in small‐cell lung carcinoma
Authors: King Peter H. , Dropcho Edward J. 
Published: January 2005

AbstractHel‐Nl and HuD are neuron‐specific RNA‐binding proteins that are antigenic targets of anti‐Hu antibodies. Although expression of Hu antigens is most commonly seen in small‐cell lung carcinoma, their exact identity (e.g., Hel‐N1, HeLN2, HuD, and HuC) cannot be distinguished by immunological methods. Analysis of messenger RNA expression is needed for this distinctian. Here we demonstrate that Hel‐Nl and Hel‐N2 are expressed in small‐cell lung carcinoma using reverse transcription‐polymerase chain reaction.
Abnormalities of smooth eye and head movement control in parhson's disease
Authors: Waterston John A. , Barnes Graham R. , Grealy Madeleine A. , Collins Sue 
Published: January 2005

AbstractThe control of horizontal head and eye movements was examined in 13 nondemented patients with Parkinson's disease (PD) of mild to moderate severity. During pursuit of single‐frequency sine waves, smooth component eye velocity was lower in the PD group at frequencies of 1.2 Hz and above; but the differences in overall eye displacement were even greater, indicating an impaired ability to generate catch‐up saccades at high frequencies. A corresponding deficit in saccadic performance was observed during a high‐frequency saccadic tracking task where predictive saccades of reduced gain and variable timing were generated. During pursuit of pseudo‐random target motion with varying degrees of predictability, small differences in smooth component eye velocity were observed, but prediction was otherwise well preserved in the patient group. Vestibulo‐ocular reflex (VOR) suppression was also normal during head‐free pursuit. No major improvement in smooth pursuit gain could be attributed to drug treatment, based on a comparison of patient results before and after administration of levodopa.
DR2/DQwl Inheritance and haplotype sharing in affected siblings from multiple sclergis families
Authors: Voskuhl Rhonda R. , Goldstein Alisa M. , Voskuhl Toni , Davey Richard J. , McFarland Henry F. 
Published: January 2005

AbstractAlthough the human leukocyte antigen DFWDQwl allele has been associated with multiple sclerosis, studies of DRZ/DQwl inheritance in multiple sclerosis multiplex families have yielded conflicting results. We examined this question in “highincidence” families, defined as families with more than 50% of siblings affected. DR2/ DQwl allele frequencies were significantly increased, particularly in mothers and affected siblings (p < 0.0001). The transmission of DR2IDQwl from both parents was more frequent in affected offspring (p = 0.005). While evidence for segregation of disease with a particular parental allele was lacking in most families, the frequency of haplotype sharing was higher in affected sib pairs (p < 0.01).
Cerebrovascular complications of Fabry's disease
Authors: Mitsias Panyiotis , Levine Steven R. 
Published: January 2005

AbstractFabry's disease (FD) is a rare, sex‐linked disorder resulting from α‐galactosidase deficiency. Cerebrovascular complications have been reported in the literature but have not been systematically analyzed. We report 2 patients and review 51 previously reported cases (descriptive meta‐analysis) to clarify the clinical, radiologic, and pathologic features. The average age at onset of cerebrovascular symptoms was 33.8 years for hemizygous individuals (n = 43) and 40.3 years of heterozygotes (n = 10). The most frequent symptoms and signs were as follows (in descending order of frequency): hemiparesis, vertigo/dizziness, diplopia, dysarthria, nystagmus, nausea/vomiting, head pain, hemiataxia, and ataxia of gait, in the hemizygote group; and memory loss, dizziness, ataxia, hemiparesis, loss of consciousness and hemisensory symptoms, in the heterozygote group. The vertebrobasilar circulation was symptomatic in 67% of the hemizygotes and 60% of the heterozygotes. Intracerebral hemorrhage was found in 4 patients (3 hemizygotes and 1 heterozygote). Elongated, ectatic, tortuous vertebral and basilar arteries were the most common angiographic and pathologic features. For the hemizygotes, the recurrence rate for cerebrovascular disease was 76% and the death rate was 55%; 86% of the heterozygotes had recurrent cerebrovascular event(s) and 40% died. The cerebrovascular manifestations of FD, in both hemizygotes and heterozygotes, are predominantly due to dilative arteriopathy of the vertebrobasilar circulation, frequently recur, and portend a poor prognosis.
Acute multiple sclerosis (marburg type) is associated with developmentally immature myelin basic protein
Authors: Wood D. D. , Moscarello M. A. , Bilbao J. M. , O'Connors P. 
Published: January 2005

AbstractWe have studied a case of acute, fulminating multiple sclerosis (MS) (Marburg type) at the pathological and biochemical levels. Postmortem examination of the brain revealed extensive areas of gross rarefaction in the hemispheric white matter. Histologically, well‐demarcated areas of demyelination with a large influx of macrophages and a subtle perivascular infiltration of lymphocytes were seen with relative preservation of the axis cylinders. Myelin basic protein (MBP) was isolated and purifed from noninvolved white matter. It was slightly larger in molecular weight than MBP from normal brain or from chronic MS brain. The increase in mass was accounted for, in part, by the deimination of 18 of 19 arginyl residues to citrulline, making the patient's MBP much less cationic than MBP from normal white matter. When expressed as the ratio of least cationic form of MBP to the most cationic (C‐8/C‐1), the normal ratio was 0.82, chronic MS 2.5, and the patient in this study 6.7. Because the ratio of 6.7 was similar to 7.5 found for a 15‐month‐old infant, MBP was considered to be of the immature form. The data are consistent with a genetic factor influencing the charge microheterogeneity of MBP. The resulting less cationic MBP cannot carry out its normal function of compacting multilayers.
Language cortex representation: Effects of developmental versus acquired pathology
Authors: Duchowny Michael , Jayakar Prasanna , Harvey A. Simon , Resnick Trevor , Alvarez Luis , Dean Patricia , Levin Bonnie 
Published: January 2005

AbstractRelatively little is known about language cortex representation in patients with developmental pathology and epilepsy. We report the results of mapping language by electrical stimulation of chronically implanted subdural electrodes in 34 patients (mean age, 12.2 years) evaluated for epilepsy surgery, 28 of whom had magnetic resonance imaging or histological evidence of developmental tumors or cortical dysplasia. Language cortex was identified in the temporal or frontal lobe of 19 patients (left hemisphere in 17, right hemisphere in 2), and overlapped or bordered the epileptogenic region in 12. Language cortex was not found in the frontal or temporal lobe of 15 patients (left hemisphere in 4, right hemisphere in 11) and was presumed to be contralateral to grid placement. Three patients with left‐hemisphere perinatal or postnatal cerebral insults before the age of 5 years had no language in the left hemisphere, while 3 patients with insults between the ages of 6 and 16 years had preserved left‐hemisphere language. Developmental lesions and early onset seizures do not displace language cortex from prenatally determined sites, whereas lesions acquired before the age of 5 years may cause language to relocate to the opposite hemisphere, but only when language cortex is destroyed.
Cortical myoclonus in angelman syndrome
Authors: Guerrini Renzo , Bonanni Paolo , de Lorey Timothy M. , Serratosa José M. , Moncla Anne , Malzac Perrine , Dravet Charlotte , Igvet Marie Odile , Bureau Michelle , Genton Pierre , Suisse Georges , Thomas Pierre , Sartucci Ferdinando , Simi Paolo 
Published: January 2005

AbstractAngelman syndrome (AS) results from lack of genetic contribution from maternal chromosome 15q11–13. This region encompasses three GABAA receptor subunit genes (β3, α5, and γ3). The characteristic phenotype of AS is severe mental retardation, ataxic gait, tremulousness, and jerky movements. We studied the movement disorder in 11 AS patients, aged 3 to 28 years. Two patients had paternal uniparental disomy for chromosome 15, 8 had a <3 Mb deletion, and 1 had a microdeletion involving loci D15S10, D15S113, and GABRB3. All patients exhibited quasicontinuous rhythmic myoclonus mainly involving hands and face, accompained by rhythmic 5‐ to 10‐Hz electroencephalographic (EEG) activity. Electromyographic bursts lasted 35 ± 13 msec and had a frequency of 11 ± 2.4 Hz. Burst‐locked EEG averaging in 5 patients, generated a premyoclonus transient preceding the burst by 19 ± 5 msec. A cortical spread pattern of myoclonic cortical activity was observed. Seven patients also demonstrated myoclonic seizures. No giant somatosensory evoked potentials or C‐reflex were observed. The silent period following motor evoked potentials was shortened by 70%, indicating motor cortex hyperexcitability. Treatment with piracetam in 5 patients significantly improved myoclonus. We conclude that spontaneous, rhythmic, fast‐bursting cortical myoclonus is a prominent feature of AS.
Striatal D1 and D2 dopamine receptor loss in asymptomatic mutation carriers of Huntington's disease
Authors: Weeks R. A. , Piccini P. , Harding A. E. , Brooks D. J. 
Published: January 2005

AbstractWe have investigated striatal dopamine D1 and D2 receptor binding in asymptomatic subjects from Huntington's disease (HD) families using positron emission tomography. Nineteen adult subjects at risk of developing HD were scanned with 11C‐SCH 23390 and 11C‐raclopride to calculate the D1 and D2 receptor binding potential, respectively. Eight of the 19 were shown to have the HD mutation; of these, 4 subjects had significant reductions in striatal dopamine receptor binding. Abnormalities were more common in older subjects and were not correlated with the size of the HD mutation. There was a strong coefficient of correlation between individual levels of striatal D1 and D2 binding in subjects with the mutation. Of 6 other cases with a 50% risk of carrying the HD gene, 1 showed subclinical loss of caudate and putamen D2 binding. Our study suggests that both striatal D1 and D2 dopamine receptors are lost in parallel from both cauudate and putamen in presymptomatic HD and that dopamine receptor binding provides a sensitive means of detecting subclinical striatal dysfunction.
X‐linked nonprogressive congenital cerebellar hypoplasia: Clinical description and mapping to chromosome Xq
Authors: Illarioshkin Sergei N. , Tanaka Hajime , Tsuji Shoji , Markova Elena D. , Nikolskay Natalya N. , Ivanova‐Samolenskay Irina A. 
Published: January 2005

AbstractWe examined a large family in which an X‐linked recessive congenital ataxia manifested in 7 males from three generations. The affected boys first exhibited a marked delay of early developmental motor milestones. A neurological syndrome became evident by 5 to 7 years of age and included cerebellar ataxia, dysarthria, and external ophthalmoplegia; there were no symptoms of mental retardation, spastic paraparesis, or sensory loss. Neuroimaging studies revealed hypoplasia of cerebellar hemispheres and vermis. The disease showed no progression beyond early childhood. The unique heredity and clinical features clearly distinguish this new entity from a variety of previously described familial ataxias. Pairwise linkage analysis and haplotype reconstruction allowed us to map the gene responsible for this disorder to a 38‐cM interval on chromosome Xp11.21‐q24 flanked by the loci DXS991 and DXS1001. Upon multipoint linkage analysis, the disease gene was determined to be located most likely in the proximal part of chromosome Xq, with the maximal lod score of 4.66 at the locus DXS1059 (Xq23). This is the first example of the genetic mapping of a pure congenital cerebellar hypoplasia syndrome.
Multiple mutations in the GALC gene in a patient with adult‐onset krabbe disease
Authors: Luzi Paola , Rafi Mohammad A. , Wenger David A. 
Published: January 2005

AbstractA 53‐year‐old man was diagnosed 8 years earlier with globod cell leukodystrophy (GLD, Krabbe disease) by his severe deficiency of galactocerebrosidase (GALC) activity. He was found to have eight nucleotide changes on the two copies of his GALC gene, including two in the leader sequence, four considered polymorphisms, and two unique mutations.
Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43)
Authors: Mann D. M. A. , Iwatsubo T. , Cairns N. J. , Lantos P. L. , Nochlin D. , Sumi S. M. , Bird T. D. , Poorkaj P. , Hardy J. , Hutton M. , Prihar G. , Crook R. , Rossor M. N. , Haltia M. 
Published: January 2005

AbstractAmyloid β protein (Aβ) deposition was investigated in the frontal cortex of 8 cases of (genetically confirmed) chromosome 14–linked Alzheimer's disease (AD) using the end‐specific monoclonal antibodies BA27 and BC05 to detect the presnce of Aβ40 and Aβ42(43), respectively. IN all patients, Aβ42(43) was the predominant peptide species present. The total amount of Aβ40 and Aβ42(43) deposited was more than twice the amount deposited in cases of sporadic AD of similar disease duration, although the ratio between the extent of Aβ40 and Aβ42(43) deposition was unaltered, compared with sporadic AD. Therefore, (one of) the effects of the mutations in the presenilin 1:PS‐1 (S182) gene may be to cause or at least promote an early and excessive deposition of Aβ42(43) within the brain, a property shared with other inherited forms of AD, such as those due to amyloid precursor protein mutations, and Down's syndrome (trisomy 21).
Mitochondrial DNA and RNA processing in MELAS
Authors: Kaufmann Petra , Shanske Sara , Hirano Michio , DiMauro Salvatore , King Michael P. , Koga Yasutoshi , Schon Eric A. 
Published: January 2005

AbstractMitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes (MELAS), a maternally inherited disorder, is usually associated with a point mutation in mitochondrial DNA (mtDNA) at position 3,243 in the tRNALeu(UUR) gene. To further study the pathogenesis of MELAS, we analyzed tissues from 8 MELAS‐3,243 patients. Southern blot anlaysis showed an increase in the ratio of mtDNA to nuclear DNA in almost all tissues examined, implying that mitochondrial proliferation is ubiquitous and is not confined to ragged‐red fibers in muscle. By northern blot analysis, we demonstrated increased steady‐state levels of RNA 19, a polycistronic transcript corresponding to the 16S rRNA + tRNALeu(UUR) + ND1 genes (which are contiguous in the mtDNA) in heart, kidney, and musscle. These results provide further evidence that altered mitochondrial nucleic acid metabolism may have pathogenic significance in MELAS.
Familial temporal lobe epilepsy: A common disorder identified in twins
Authors: Berkovic Samuel F. , McIntosh Anne , Howell R. Anne , Mitchell Anne , Sheffield Leslie J. , Hopper John L. 
Published: January 2005

AbstractWe describe a new syndrome of familial temporal lobe epilepsy in 38 individuals from 13 unrelated white families. The disorder was first identified in 5 concordant monozygotic twin pairs as part of a large‐scale twin study of epilepsy. When idiopathic partial epilepsy syndromes were excluded, the 5 pairs accounted for 23% of monozygotic pairs with partial epilepsies, and 38% of monozygotic pairs with partial epilepsy and no known etiology. Seizure onset for twin and nontwin subjects usually occurred during adolescence or early adult life. Seizure types were simple partial seizures with psychic or autonomic symptoms, infrequent complex partial seizures, and rare secondarily generalized seizures. Electroencephalograms revealed sparse focal temporal interictal epileptiform discharges in 22% of subjects. Magnetic resonance images appeared normal. Nine affected family members (24%) had not been diagnosed prior to the study. Pedigree analysis suggested autosomal dominant inheritance with age‐dependent penetrance. The estimated segregation ratio was 0.3, indicating an overall penetrance of 60% assuming autosomal dominant inheritance. The mild and often subtle nature of the symptoms in some family members may account for lack of prior recognition of this common familial partial epilepsy. This disorder has similarities to the El mouse, a genetic model of temporal lobe epilepsy with a major gene on mouse chromosome 9, which is homologous with a region on human chromosome 3.