bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machado‐joseph disease: Clinical, molecular, and metabolic characterization in chinese kindreds
Authors: Soon Bing‐wen , Cheng Chung‐Hui , Liu Ren‐Shyan , Shan Din‐E 
Published: January 2005

AbstractMachado‐Joseph disease, an autosomal dominant multisystem motor degeneration, has been described mainly in people of Portuguese descent. Our report documents the presence of Machado‐Joseph disease in the Chinese population, based on the specific molecular marker of a CAG repeat array in the 3′ end of the MJD gene. We screened 21 Chinese families with dominant spinocerebellar ataxia. The results showed that Machado‐Joseph disease with CAG expansion accounted for 52% of families with autosomal dominant cerebellar ataxia in this series. The clinical characteristics, besides the well‐documented cerebellar ataxia, dysarthria, nystagmus, corticospinal dysfunctions, a variable degree of facial muscle fasciculation, and proprioceptive loss, included loss of optokinetic nystagmus and autonomic nervous system dysfunction. The CAG repeat number in the MJD gene ranged from 14 to 39 among normal alleles, and from 63 to 81 among MJD alleles. There was a strong inverse correlation (γ = –0.77) between number of CAG repeats and age at symptom onset, accounting for 60% of the variance of age at onset. A strong clinical anticipation of age at onset existed in successive generations. Mild instabilities of expanded CAG repeat numbers during meiotic transmission occurred, with no significant difference according to the gender of the transmitting parent. Finally, brain metabolism in Machado‐Joseph disease, studied with positron emission tomography, was characterized by significant progressive regional hypometabolism in the occipital cortex, as well as the cerebellar hemispheres, vermis, and brainstem.
Expression of the copper‐zinc superoxide dismutase gene in amyotrophic lateral sclerosis
Authors: Nishiyama Kazutoshi , Murayama Shigeo , Kwak Shin , Kanazawa Ichiro 
Published: January 2005

AbstractThe demonstration of a genetic linkage between the copper‐zinc superoxide dismutase (SOD1) gene and familial amyotrophic lateral sclerosis has aroused interest in the role of SOD1 in motoneuronal death. We investigated the expression of the human SOD1 gene at a cellular level in the motoneurons of patints with sporadic amytrophic lateral sclerosis, patients with familial amyotrophic lateral sclerosis, and normal control subjects, using a quantitative insitu hybridization technique. There were no significant differences between the amountf os SOD1 messenger RNA observed in patints wtih sporadic disease, patients with familial disease, and normal control subjects. However, many of the atrophic motoneurons from patients with sporadic or familial disease had significantly lower levls of SOD1 messenger RNA, compared to morphologically intact motoneurons. Moreover, motoneurons in the normal spinal ventral horn and precentral motor cortex exhibited significantly higher levels of SOD1 messenger RNA than did other neurons. Our study indicated that vulnerable neurons in amyotrophic lateral sclerosis exhibit high levels of SOD1 messenger RNA, suggesting a close relatioship between the SOD1 gene and the pathogenesisof amyotrophic lateral sclerosis.
Enlargement of human cerebral ischemic lesion volumes measured by diffusion‐weighted magnetic resonance imaging
Authors: Baird Alison E. , Benfield Andrew , Schlaug Gottfried , Siewert Bettina , Lövblad Karl‐Olof , Edelman Robert R. , Warach Steven 
Published: January 2005

AbstractWe aimed to determine the frequency and time course of the enlargement of ischemic cerebral lesions following human stroke and to study the effect of the state of perfusion on lesion enlargement. Acute lesion volumes were measured on diffusion‐weighted magnetic resonance images and compared with lesion volumes measured on T2‐weighted images at 7 days or later. Forty‐four measurements were performed between 2 and 53 hours after stroke onset in 28 patients. Thirteen patients also had magnetic resonance perfusion imaging performed. In 12 (43%) of 28 patients the initial lesion volume increased by 20% or more. The number of studies showing enlargement of the ischemic lesion volume ranged from 12 (43%) of 28 at or after 2 hours to 10 (38%) of 26 at or after 6 hours, 5 (33%) of 15 at or after 24 hours, and 2 (33%) of 6 at or after 48 hours. In 7 of the 10 patients in whom the hypoperfusion volume acutely exceeded the volume of the abnormality on diffusion‐weighted images, lesion volume increased by 20% or more. This study provided evidence that substantial enlargement of human cerebral ischemic lesion volumes can occur beyond the first 6, 12 or 24 hours after onset. A mismatch acutely between the region of hypoperfusion (larger) and the region of diffusion abnormality (smaller) may be predictive of ischemic lesion enlargement.
Brain impairment in well‐nourished chronic alcoholics is related to ethanol intake
Authors: Nicolás Josep M. , Estruch Ramón , Salamero Manel , Orteu Nuria , Fernandez‐Solà Joaquim , Sacanella Emilio , Urbano‐Márquez Alvaro 
Published: January 2005

AbstractTo determine the influence of chronic ethanol intake on the central nervous system, we studied 40 asymptomatic, well‐nourished, chronic alcoholics (mean age, 42.6 ± 9.1 years) and 20 age‐, sex‐, and education‐matched control subjects. Studies included neuropsychological testing, visual and short‐latency auditory evoked potentials, and morphometric analysis of computed tomography scans. The mean daily ethanol consumption of the alcoholics was 204 gm over an average of 26.4 years. Compared to control subjects, chronic alcoholics exhibited a significant prolongation of the P100 latency of visual evoked potentials, and a prolongation and reduction in the amplitude of the latency of the V wave of short‐latency auditory evoked potentials. These abnormalities were related to the lifetime dose of ethanol consumed. Brain morphometric analysis showed that alcoholics had a significantly greater degree of brain shrikage with age, compared to control subjects. The cortical atrophy index correlated significantly with the lifetime ethanol consumption. Neuropsychological testing in alcoholics compared to controls revealed a significant impairment of frontal skills that was related to age, degree of scholarship, and the presence of frontal atrophy. In conclusion, well‐nourished chronic alcoholics exhibited a significant brain impairment, as demonstrated by neuropsychological testing, evoked potentials, and brain morphometric analysis, which was correlated with the lifetime dose of ethanol consumed.
The absence of an apolipoprotein ϵ4 allele is associated with a more aggressive form of Alzheimer's disease
Authors: Stern Yaakov , Brandt Jason , Albert Marilyn , Jacobs Diane M. , Liu Xinhua , Bell Karen , Marder Karen , Sano Mary , Albert Steven , Castenada Caridad Del‐Castillo , Bylsma Fred , Tycko Ben , Mayeux Richard 
Published: January 2005

AbstractWe investigated the relationship between APOE genotype and rate of disease progression and survival in 99 patients with probable Alzheimer's disease (AD) who were followed biannually for up to 6 years. Patients were stratified into two groups, those with and without at least one APOE ϵ4 allele. The rate of decline in modified Mini‐Mental State Examination scores was slower, the presence of extrapyramidal signs was decreased, and the development of myoclonus occurred later among patients with APOE ϵ4 alleles compared with patients with other genotypes. Compared with patients with other genotypes. Compared with patients without an APOE ϵ4 allele, the risk of mortality was also decreased in patients with at least one ϵ4 allele (RR = 0.38; CI = 0.17−0.84, P < 0.02). Because the decline in mental ability as well as the development of myoclonus and extrapyramidal signs are consistent manifestations of disease progression, our results imply that APOE ϵ4 is associated with a less aggressive form of AD.
Juvenile‐onset spinal muscular atrophy caused by compound heterozygosity for mutations in the HEXA gene
Authors: Navon Ruth , Khosravi Rami , Melki Judith , Drucker Liat , Fontaine Bertrand , Turpin Jean Claude , N'Guyen Bathein , Fardeau Michel , Rondot Pierre , Baumann Nicole 
Published: January 2005

AbstractProgressive proximal muscle weakness is present both in spinal muscular atrophy (SMA) type III (Kugelberg‐Welander disease) and in GM2 gangliosidosis, diseases that segregate in an autosomal recessive fashion. The SMN gene for SMA and the HEXA gene for GM2 gangliosidosis were investigated in a woman with progressive proximal muscle weakness, long believed to be SMA type III (Kugelberg‐Welander type). She and her family underwent biochemical studies for GM2 gangliosidosis. Analysis of SMN excluded SMA. Biochemical studies on GM2 gangliosidosis showed deficiency in hexosaminidase A activity and increased GM2 ganglioside accumulation in the patient's fibroblasts. The HEXA gene was first analyzed for the Gly269→Ser mutation characteristic for adult GM2 gangliosidosis. Since the patient was carrying the adult mutation heterozygously, all 14 exons and adjacent intron sequences were analyzed. A novel mutation in exon 1 resulting in an A‐to‐T change in the initiation codon (ATG to TTG) was identified. The adult patient is a compound heterozygote, with each allele containing a different mutation. Although mRNA was transcribed from the novel mutant allele, expression experiments showed no enzyme activity, suggesting that neither the TTG nor an alternative codon serve as an initiation codon in the HEXA gene.
Phenotypic variability in friedreich ataxia: Role of the associated GAA triplet repeat expansion
Authors: Montermini Laura , Richeter Andrea , Morgan Kenneth , Justice Cristina M. , Julien Dominique , Castellotti Barbara , Mercier Jocelyne , Poirier Josée , Capozzoli Fiorentino , Bouchard Jean‐Pierre , Lemieux Bernard , Mathieu Jean , Vanasse Michel , Seni Marie‐Hélene , Graham Gail , Andermann Frederick , Andermann Eva , Melançon Serge B. , Keats Bronya J. B. , Di Donato Stefano , Pandolfo Massimo 
Published: January 2005

AbstractWe studied genotype‐phenotype correlations in a group of 100 patients with typical Friedreich ataxia (FRDA), and in three groups of patients with atypical clinical presentations, including 44 Acadian FRDA, 8 late‐onset FRDA (LOFA), and 6 FRDA with retained reflexes (FARR). All patients, except 3 with typical FRDA, carried two copies of the FRDA‐associated GAA triplet repeat expansion. Overall, the phenotypic spectrum of FRDA appeared to be wider than defined by the currently used diagnostic criteria. Our study indicated the existence of several sources of variability in FRDA. Patients with larger GAA expansions tended to have earlier onset and were more likely to show additional manifestations of the disease. Mitotic instability of the expanded GAA repeats may partially account for the limited degree of correlation between expansion sizes as determined in lymphocytes and clinical parameters. Some clinical variants associated with specific FRDA haplotypes, such as Acadian FRDA and FARR, turned out to be unrelated to expansion sizes. No polymorphism in the frataxin coding sequence could be associated with these clinical variants.
A new type of hereditary motor and sensory neuropathy linked to chromosome 3
Authors: Takashima Hiroshi , Nakagawa Masanori , Nakahara Keiichi , Suehara Masahito , Matsuzaki Toshio , Higuchi Itsuro , Higa Hidemasa , Arimura Kimiyoshi , Iwamasa Teruo , Izumo Shuji , Osame Mitsuhiro 
Published: January 2005

AbstractWe report the clinical, pathological, and genetic findings of 23 patients in 8 families with hereditary motor and sensory neuropathy (proximal dominant form) (HMSN‐P) in Okinawa, Japan. The clinical features were unique with respect to autosomal dominant inheritance, Kennedy‐Alter‐Sung syndrome‐like proximal dominant neurogenic atrophy, obvious sensory involvement, painful muscle cramp, fasciculations, areflexia, and high incidences of elevated creatine kinase levels, hyperlipidemia, and diabetes mellitus. Electrophysiological and pathological studies revealed typical motor and sensory axonal neuropathy, and decreased numbers of anterior horn and dorsal ganglion cells, which suggested the presence of neuronopathy in HMSN‐P. Genetic linkage studies showed a lod score of 4.04 (two‐point analysis) in DNA marker D3S1284. Haplotype analysis showed that the gene locus of the disease was mapped to 3p14.1‐q13 bracketed by D3S1285 and D3S1281. In this region, the patients' chromosomes showed an obvious increase in the allele frequency of five markers. One allele in D3S1591 was identical in all patients but had a low frequency in the control population. This finding suggested the presence of linkage disequilibrium and a common origin of this allele in all patients with HMSN‐P. The HMSN‐P described here is a new clinical entity characterized by unique clinical manifestations and a new gene locus.
Human T‐cell lymphotropic virus type I‐associated facial nerve palsy in trinidad and tobago
Authors: Bartholomew Courtenay , Cleghorn Farley , Jack Noreen , Edwards Jeffrey , Blattner William 
Published: January 2005

AbstractTo assess the association of the human T‐cell lymphotropic virus type I (HTLV‐I) and idiopathic facial nerve palsy of the lower motor neuron type, we studied 78 patients consecutively admitted to the Port of Spain General Hospital in Trinidad, the West Indies, with a confirmed diagnosis of idiopathic facial nerve palsy. Patients were compared with two control groups: a population‐based group of persons 20 years and older and a hospital‐based group of patients 15 to 84 years old admitted to the medical wards. Sixty‐two patients were Trinidadians of African origin and 16 were Trinidadians of East Indian origin. None of the East Indian patients was HTLV‐I antibody positive. Three Afro‐Trinidadians were infected with human immunodeficiency virus type 1 and 1 was coinfected with this virus and HTLV‐I. Of the remaining 58 Afro‐Trinidadians, 12 (20.7%) were HTLV‐I positive only. This rate was statistically higher than the HTLV‐I seroprevalence in the Afro‐Trinidadian general population (3.5%) and the hospital control group (5.6%). After age standardization, the HTLV‐I prevalence for patients with facial nerve palsy remained significantly elevated. HTLV‐I antibody assays should be performed on all patients with idiopathic facial nerve palsy of the lower motor neuron type who live in HTLV‐I endemic areas or are migrants from these areas.
Is there a genetic susceptibility locus for Parkinson's disease on chromosome 22q13?
Authors: Wilhelmsen K. , Mirel D. , Marder K. , Bernstein M. , Naini A. , Leal S. M. , Cote L. J. , Tang M.‐X. , Freyer G. , Graziano J. , Mayeux R. 
Published: January 2005

AbstractThe cytochrome P450 mono‐oxygenase gene, CYP2D6 on chromosome 22q13 (ch22q13), has been inconsistently associated with Parkinson's disease. Associations with CYP2D6 have either been absent altogether or have involved more than one polymorphism, many of which have the same metabolic effect on gene expression. We examined the association between CYP2D6 polymorphisms and Parkinson's disease in a case‐control study and included 10 polymorphic dinucleotide repeat markers linked to CYP2D6 to determine whether the association was present or due to linkage disequilibrium. There was no association between any polymorphism of CYP2D6 and Parkinson's disease, but two of 10 dinucleotide repeat markers linked to CYP2D6 were associated with the disease. These results provide evidence to suggest that there may be an unidentified locus for susceptibility to Parkinson's disease that is in linkage disequilibrium with dinucleotide repeat markers mapping near CYP2D6 on ch22q13.
α1‐Antichymotrypsin as a risk modifier for late‐onset Alzheimer's disease in Japanese apolipoprotein E ε4 allele carriers
Authors: Yoshiiwa A. , Kamino K. , Yamamoto H. , Kobayashi T. , Imagawa M. , Nonomura Y. , Yoneda H. , Sakai T. , Nishiwaki Y. , Sato N. , Rakugi H. , Miki T. , Ogihara T. 
Published: January 2005

AbstractIn the Japanese population, sporadic late‐onset Alzheimer's disease (LOAD) cases had significantly higher frequencies of the A allele of α1−antichymotrypsin (ACT) gene as well as the $4 allele of apolipoprotein E (APOE) gene than controls. The odds ratio for LOAD in APOE4 carriers with the ACT‐A allele was more than six times that in APOE4 carriers without the ACT‐A allele (21.1 vs 3.2). These results indicate that the ACT‐A allele is a risk modifier for LOAD in APOE4 carriers.
A biochemical, genetic, and clinical survey of autosomal recessive limb girdle muscular dystrophies in Turkey
Authors: Dincer Pervin , Leturcq France , Richard Isabelle , Piccolo Federica , Yalnizoàlu Dilek , De Toma Claudia , Akçören Zuhal , Broux Odile , Deburgrave Nathalie , Brenguier Lydie , Roudaut Carinne , Urtizberea J. Andoni , Jung Daniel , Tan Ersin , Jeanpierre Marc , Campbell Kevin P. , Kaplan Jean‐Claude , Beckmann Jacques S. , Topaloàlu Haluk 
Published: January 2005

AbstractAutosomal recessive limb girdle muscular dystrophy (LGMD2) is a clinically and genetically heterogenous group of diseases involving at least six different loci. Five genes have already been identified: calpain‐3 at LGMDA2A (15q15), and four members of the sarcoglycan (SG) complex, α‐SG at LGMD2D (17q21), β‐SG at LGMD2A (4q12), γ‐SG at LGMD2C (13q12), and dL‐SG at LGMD2F (5q33–q34). The gene product at LGMD2B (2p13–p16) is still unknown and at least one other gene is still unmapped. We investigated 20 Turkish families (18 consanguineous) diagnosed as having LGMD2. Most of our patients had onset of symptoms before age 10. The phenotypes varied from severe to benign. We analyzed the SG complex by immunofluorescence and/or western blot. Genotyping was performed using markers defining the six known loci and the suspected genes were screened for mutations. Six of 17 index cases showed deficiency of the SG complex, by immunofluorescence and/or western blot. Seven cases involved on e of the known genes of the SG complex (α, 2; β, 1; and γ, 4 cases), and five mutations were documented in the α‐ and γ‐SG genes. After linkage analysis, 10 families were characterized as having LGMD2A (calpain‐3 deficiency), and all mutations were eventually identified. One family was classified as having LGMD2B and 1 family that has normal SGs was linked to the chromosome 5q33–q34 locus (LGMD2F). In 1 family there was no linkage to any of the known LGMD2 loci. It appears that in Turkey, there is a broad spectrum of genes and defects involved in LGMD2. It may be possible to correlate genotype to phenotype in LGMD2. All severe cases belonged to the γ‐SG–deficiency group. Nine calpain‐3–deficient cases had intermediate and 1 had moderate clinical courses. The LGMD2B patient had a moderate clinical expression, whereas the LGMD2F case was truly benign.
Immune deviation following pulse cyclophosphamide/methylprednisolone treatment of multiple sclerosis: Increased interleukin‐4 production and associated eosinophilia
Authors: Smith Derek R. , Balashov Konstantin E. , Hafler David A. , Khoury Samia J. , Weiner Howard L. 
Published: January 2005

AbstractMultiple sclerosis (MS) is postulated to be a Th1‐type cell‐mediateds autiommune disease. Thus therapies that decrease T cell interferon (IFN)‐γ production or increase interleukin (IL)‐4 production would be expected to have an ameliorating effect on MS. Some progressive MS patients receiving pulse cyclophosphamide therapy developed periheral blood eosinophilia. We investigated whether cyclophosphamide‐treated patients had immune deviation toward Th2 responses. We measured cytokine production in patients receiving either monthly intravenous methylprednisolone (MP), intravenous cyclophosphamide plus methylprednisolone (CY/MP), methotrexate, IFN‐β1b, in untreated MS patients, and in healthy controls. Minimal IL‐4 was secreted in untreated patients (129 · 62 pg/ml), methotrexate‐treated patients (99 · 79 pg/ml), and healthy controls (50 · 13 pg/ml). A marked increase in IL‐4 was observed in CY/MP patients (1,503 · 291 pg/ml). Patients treated with MP (418 · 160 pg/ml) or IFN‐β1b (425 · 167 pg/ml) showed small increases. Eosinophilia in CY/MP‐treated patients (6.0 · 0.7%) correlated with increased IL‐4. IL‐10 production was also increased in CY/MP‐treated patients. Both CY/MP‐ and MP‐treated groups had decreased production of IFN‐γ compared with untreated MS. These findings demonstrate pronounced immune deviation favoring Th2‐type responses after pulse cyclophosphamide therapy.
Pathological τ proteins in postencephalitic parkinsonism: Comparison with Alzheimer's disease and other neurodegenerative disorders
Authors: Buée‐Scherrer Valérie , Buée Luc , Leveugle Bátrice , Perl Daniel P. , Vermersch Patrick , Hof Patrick R. , Delacourte André 
Published: January 2005

AbstractImmunohistochemical and biochemical analyses of hyperphosphorylated τ proteins, the major component of neurofibrillary tangles, were performed in different brain regions from patients presenting with postencephalitic parkinsonism. Neurofibrillary tangles were found in hippocampus, neocortical areas (mostly in supragranular layers), and several subcortical structures. By immunobloting, a τ protein triplet similar to the one seen in Alzheimer's disease was observed. This biochemical approach allows for the definition of postencephalitic parkinsonism from certain neurodegenerative disorders such as progressive supranuclear palsy and corticobasal degeneration.
Huntingtin localization in brains of normal and Huntington's disease patients
Authors: Sapp E. , Schwarz C. , Chase K. , Bhide P. G. , Young A. B. , Penney J. , Vonsattel J. P. , Aronin N. , DiFiglia M. 
Published: January 2005

AbstractThe immunohistochemical localization of huntingtin was examined in the Huntington's disease (HD) brain with an antibody that recognizes the wild‐type and mutant proteins. Neuronal staining was reduced in areas of the HD striatum depleted of medium‐sized neurons; large striatal neurons, which are spared in HD, retained normal levels of huntingtin expression. Neuronal labeling was markedly reduced in both segments of the globus pallidus including in brains with minimal loss of pallidal neurons. In some HD cortical and striatal neurons with normal looking morphology, huntingtin was associated with punctate cytoplasmic granules that at the ultrastructural level resembled the multivesicular body, an organelle involved in retrograde transport and protein degradation. Some immunoreactive processes showed blebbing and segmentation similar to that induced experimentally by hypoxic–ischemic or excitotoxic injury. Huntingtin staining was more concentrated in the perinuclear cytoplasm and reduced or absent in processes of atrophic cortical neurons. Nuclear staining was also evident. Fibers in the subcortical white matter of HD patients had significantly increased huntingtin immunoreactivity compared with those of controls. Results suggest that there may be changes in the neuronal expression and transport of wild‐type and/or mutant huntingtin at early and late stages of neuronal degeneration in affected areas of the HD brain.