bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple mitochondrial DNA deletions in sporadic inclusion body myositis: A study of 56 patients
Authors: Santorelli F. M. , Sciacco M. , Tanji K. , Shanske S. , Vu T. H. , Golzi V. , Griggs R. C. , Mendell J. R. , Hays A. P. , Bertorini T. E. , Pestronk A. , Bonilla E. , Dimauro S. 
Published: January 2005

AbstractInclusion body myositis, a chronic inflammatory disorder, is the most common cause of myopathy in adults over the age of 50. Diagnosis is based on clinical features and distinctive morphological findings by both light and electron microscopy. The causes of inclusion body myositis are still unknown. Ultrastructural mitochondrial changes and ragged‐ red fibers are common in patients with sporadic inclusion body myositis, and mutiple mitochondrial DNA (mtDNA) deletions have been reported in 3 such patients, suggesting that mtDNA mutations may have a pathogenetic role. We studied 56 patients with sporadic inclusion body myositis, using a combination of clinical, morphological, biochemical, and molecular genetic analyses to determine the frequency and the distribution of mtDNA deletions. Using the polymerase chain reaction, we found multiple mtDNA deletions in 73% of patients, compared to 40% of normal age‐matched control subjects and 47% of disease control subjects. The presence of deletions correlated with morphological evidence of ragged‐red, cytochrome c oxidase‐negative fibers, and with defects of complexes I and IV of the electron transport chain. Although aging may account for a proportion of mtDNA deletions in patients with sporadic inclusion body myositis and control subjects, mtDNA alterations may be accelerated in sporadic inclusion body myositis.
Familial cerebral cavernous angioma: A gene localized to a 15‐cm interval on chromosome 7q
Authors: Gil‐Nagel A. , Dubovsky J. , Wilcox K. J. , Stewart J. M. , Anderson V. E , Leppik I. E , Orr H. T , Johnson E. W , Weber J. L. , Rich S. S. 
Published: January 2005

AbstractCerebral cavernous angiomas are collections of closely clustered vessels without intervening normal brain parenchyma, with microscopic evidence of hemorrhage, frequently multiple; they are best visualized with magnetic resonance imaging. Familial cerebral cavernous angioma occurs as an autosomal dominant disorder, although carriers of the gene are often asymptomatic. Recently, a gene responsible for familial cerebral cavernous angioma in a large Hispanic kindred was mapped to human chromosome 7qll‐22, representing a large segment of DNA containing approximately 33 CM (about 33 million base pairs). This distance did not allow more restricted isolation of the region containing the familial cerebral cavernous angioma gene. In this report, we present a large white kindred with familial cerebral cavernous angioma and confirm the mapping to 7qll‐22, including the genetic markers D7S558/D7S1789 and D7S804. Recombination between several markers in the region suggests that the candidate region is distal to D7S804. Combining our results with those previously published, we suggest that the gene is likely to reside within a 15‐cM region bounded by markers D7S660 and D7S55WD7S1789. These results should assist the further refinement of the candidate region for familial cerebral cavernous angioma and facilitate the search for the gene.
Apolipoprotein E and cognitive change in an elderly population
Authors: Hyman B. T. , Gomez‐Isla T. , Briggs M. , Chung H. , Nichols S. , Kohout F. , Wallace R. 
Published: January 2005

AbstractThe apolipoprotein E (apoE) ε4 allele is overrepresented, and the apoE ε2 allele underrepresented, in Alzheimer's disease. To assess the risk of cognitive impairment in individuals with these genotypes in the general population, we studied a population‐based sample of 1,899 individuals 65 years and older as a follow‐up to the Iowa 65+ Rural Health Study. Multiple regression and logistic regression analyses demonstrated significant effects of apoE ε4 and apoE ε2 in predicting performance on a delayed recall task over a 4‐ to 7‐year period. The magnitude of this effect was, however, fairly modest, with odds ratios for developing impairment of approximately 1.37 (95% confidence interval: 1.007, 1.850; p = 0.045) for apoE ε4 and 0.53 (95% confidence interval: 0.368, 0.777; p = 0.001) for apoE ε2. These effects were more pronounced in women than men. Importantly, 85% of elderly apoE ε4/4 individuals (average age, 81) scored in the unimpaired range on a screening mental status test. Thus, many individuals reach old age without cognitive impairment despite inheritance of one or two apoE ε4 alleles. This suggests that apoE genotyping will have limited utility as a diagnostic or prognostic indicator of cognitive decline in individuals.
Recovery of sympathetic skin responses after digit‐to‐digit replantation and toe‐to‐digit transplantation in humans
Authors: Chu Nai‐Shin 
Published: January 2005

AbstractSympathetic skin response was utilized to study recovery of sudomotor function in 8 patients who had digit‐to‐digit replantation and 9 patients who had toe‐to‐digit transplantation. Sympathetic skin responses evoked by median nerve stimulation or magnetic stimulation of the neck were recorded from the tip of the replanted digits or transplanted toes. The contralateral normal fingers served as controls. The mean intervals between surgery and study were 33 and 37 months, respectively, for digit replantation and toe transplantation. In normal subjects, the sympathetic skin responses recorded from the fingertip were abolished by local anesthesia or cooling of the finger, while those recorded from the palm were not affected. Ischemia of the finger only transiently affected the digit sympathetic skin responses. These data indicate that the digit responses were locally generated and mediated by unmyelinated fibers. After digit replantation, the palm and digit sympathetic skin responses were not different between replanted and normal sides. After toe transplantation, palm sympathetic skin responses were normal, but digit ones had prolonged latency and reduced amplitude. The present findings suggest that recovery of sympathetic sudomotor activity can be nearly complete in digit replantation but less satisfactory in toe transplanatation.
Deficient expression in multiple sclerosis of the inhibitory transcription factor SP3 in mononuclear blood cells
Authors: Grekova Maria C. , Robinson Eve D. , Faerber Marc A. , Richert John R. , Katz Paul , McFarland Henry F. 
Published: January 2005

AbstractTo evaluate differential gene expression in multiple sclerosis (MS) patients and control subjects, we used differential display to screen for messenger RNAs that are differentially expressed in peripheral blood mononuclear cells from monozygotic twins who are discordant for MS. We identified a 232‐bp complementary DNA fragment, present only in material from the normal twin, that exhibited 100% identity with the inhibitory transcription factor Sp3. Oligonucleotide primers corresponding to Sp3 messenger RNA sequences amplified complementary DNA of appropriate size from 83% of control subjects but from only 21% of MS patients (p < 0.001). These results suggest that Sp3 gene transcription is suppressed in peripheral blood mononuclear cells from most MS patients and that other genes whose expression is normally suppressed by Sp3 in immune cells may consequently be overexpressed.
Impaired visual word processing in dyslexia revealed with magnetoencephalography
Authors: Salmelin R. , Kiesilä P. , Uutela K. , Service E. , Salonen O. 
Published: January 2005

AbstractDyslexia is most often atributed to phonological impairments, manifested in abnormal activation of the left temporal and temporoparietal cortex in response to auditorily presented language and possibly associated with anomalies in the cytoarchitecture and hemispheric symmetry of the plana temporale. The immediate cortical correlate of the severely impaired reading process has, however, remained obscure. Here we report on the distinct time courses of cortical activation in dyslexic and control subjects during passive viewing of single words, tracked with whole‐head magnetoencephalography. A striking difference was found in the left inferior temporo‐occipital region where intracranial recordings have recently identified word‐specific responses within 200 msec after stimulus onset: controls showed a sharp activation at about 180 msec after word presentation, whereas dyslexics failed to activate this area entirely, or showed a slowly increasing late response. Pereception of words as specific units thus seems to be imparied in dyslexics.
Genetic studies in Alzheimer's disease with an NACP/α‐synuclein polymorphism
Authors: Xia Yu , de Silva H. A. Rohan , Rosi Barbara L. , Yamaoka Larry H. , Rimmler Jacqueline B. , Pericak‐Vance Margaret A. , Roses Allen D. , Chen Xiaohua , Masliah Eliezer , Deteresa Richard , Iwai Akihiko , Sundsmo Mary , Thomas Ronald G. , Hofstetter C. Richard , Gregory Ethan , Hansen Lawrence A. , Katzman Robert , Thal Leon J. , Saitoh Tsunao 
Published: January 2005

AbstractThe non‐Aß component of Alzheimer's disease amyloid (NAC) is copurified with amyloid from the brain tissue of Alzheimer's disease victims and is immunohistochemically localized to amyloid fibrils. NAC is a hydrophobic peptide fragment from the NAC precursor protein (NACP/α‐synuclein) that is localized to presynaptic terminals. We used a polymorphic dinucleotide repeat sequence in a genomic clone of NACP for genetic association and linkage studies. Screening of Alzheimer's disease families failed to establish linkage between NACP and Alzheimer's disease. Nevertheless, one of the NACP polymorphisms (NACP allele 2) was shown to have significant association with healthy elderly control individuals with apolipoprotein E risk. This may indicate a possible protective function of the allele.
Genetic variability of the CYP 2D6 gene is not a risk factor for sporadic Parkinson's disease
Authors: Diederich Nico , Hilger Christiane , Hentges Francois , Metz Henri , Goetz Christopher G. , Keipes Marc , Vieregge Peter 
Published: January 2005

AbstractGenetic studies of the frequencies of mutant alleles for coding cytochrome P‐450 monooxygenase (CYP 2D6) in Parkinson's disease (PD) patients have been inconsistent. We studied the mutants A and B in 80 strictly defined sporadic PD patients divided into young age onset of the disease (<40 years, N = 20), mid age onset (40‐50 years, N = 12), and older age onset (>50 years, N = 48). They were compared with 108 controls from the same geographic area. There were no significant differences in allele or genotype frequencies between PD patients and controls. Future genetic studies in PD should focus on other alleles or other areas of the genome.
Bilateral ptosis and upgaze palsy with right hemispheric lesions
Authors: Averbuch‐Heller Lea , Stahl John S. , Remler Bernd F. , Leigh R. John 
Published: January 2005

AbstractBilateral ptosis is reported with unilateral hemispheric lesions, suggesting partial lateralization of the control of the levator palpebrae superioris. There is a tight synkinesis between vertical eye and eyelid movements, but a similar, lateralized control of vertical gaze has not been previously described. We report 3 patients with right hemispheric infarctions, in whom bilateral ptosis was accompanied by impaired upward gaze. We postulate that this laterlization of ocular motor function reflects the special contribution that the nondominant hemisphere makes to attention.
Diagnostic guidelines in central nervous system Whipple's disease
Authors: Louis E. D. , Lynch T. , Kaufmann P. , Fahn S. , Odel J. 
Published: January 2005

AbstractMany cases of central nervous system (CNS) Whipple's disease are not diagnosed until postmortem. Few reviews of CNS Whipple's disease have delineated the frequencies of abnormalities on neurological examination, cerebrospinal fluid studies, neuroimaging, and intestinal biopsy studies. Guidelines for diagnosis and treatment have not been proposed. In this review we present 3 new cases of CNS Whipple's disease and summarize the literature to determine the frequencies of neurological signs and abnormalities on diagnostic testing. We propose guidelines for diagnostic screening, selection for biopsy, and treatment. Review of the 84 cases of CNS Whipple's disease (81 in the literature, 3 new) revealed that 80% of the patients had systemic signs. Cognitive changes were frequent (71%), and 47% with cognitive changes also had psychiatric signs. Oculomasticatory myorhythmia and oculo‐facial‐skeletal myorhythmia, pathognomic for CNS Whipple's disease, were present in 20% of patients, and were always accompanied by a supranuclear vertical gaze palsy. Tissue biopsy was a sensitive technique; 89% of those who had biopsies had positive biopsy results. Diagnosis and treatment of definite CNS Whipple's disease should be based on the presence of pathognomic signs (oculomasticatory myorhythmia or oculo‐facial‐skeletal myorhythmia) or positive biopsy or polymerase chain reaction results. Possible CNS Whipple's disease should be diagnosed in the setting of unexplained systemic symptoms and neurological signs (supranuclear vertical gaze palsy, rhythmic myoclonus, dementia with psychiatric symptoms, or hypothalamic manifestations). Those with possible CNS Whipple's diseae should undergo small‐bowel biopsy.
Regional and cellular expression of the machado‐joseph disease gene in brains of normal and affected individuals
Authors: Nishiyama K. , Murayama S. , Goto J. , Watanabe M. , Hashida H. , Kanazawa I. , Katayama S. , Nakamura S. , Nomura Y. 
Published: January 2005

AbstractMachado‐Joseph disease (MJD) is an autosomal dominant disorder characterized pathologicallly by spincoerebellar degeneration. Recently, an expansion of CAG repeat in a gene located at the chromosome 14q32.1 was found to be responsible for the disease. Here, we investigated in situ the expression of the MJD gene (MJD1) in the central nervous system of normal and affected individuals and in rat brains. This gene was expressed in all regions of rat and human normal brains with certain regional variations. MJD1 was transcribed preferentially in neurons, although low levels of MJD1 mRNA were also observed in glial cells. Neurons suspectible to degeneration in MJD expressed MJD1 but not selectively. In the affected brains, the MJD1 mRNA distribution and amount in all the areas examined were similar in patients and controls. In addition, the cellular MJD1 mRNA level correlated neither with clinical severity nor expanded length. Our study showed that the expression levels of trinucleotide repeats in MJD patients and normal controls did not differ, indicating that the pathogenesis of MJD may involve direct toxicity to vulnerable subsets and/or region‐specific cofactors of MJD proteins.
Congenital muscular dystrophy with primary laminin α2 (merosin) deficiency presenting as inflammatory myopathy
Authors: Pegoraro Elena , Cianno Brad Di , Hoffman Eric P. , Mancias Pedro , Swerdlow Steven H. , Raikow Radmila B. , Garcia Carlos , Marks Harold , Crawford Thomas , Carver Virginia 
Published: January 2005

AbstractTen laminin α2‐deficient patients were identified by both immunofluorescence and immunoblotting (30% of congenital muscular dystrophy patients tested). Three of the laminin α2‐deficient patients were carrying a diagnonsis of infantile polymyositis prior to immunostaining studies. The clinical features in the 10 merosin‐deficient patients were homogeneous, with severe floppiness at birth, delay in achievement of motor milestones, and magnetic resonance imaging findings of white matter changes with normal intelligence. The 10‐kb laminin α2‐coding sequence was screened for causative mutations by reverse transcriptase‐polymerase chain reaction/single‐stranded confronmational polymorphism analysis in muscle biopys specimens from 5 patients, followed by automatic sequencing of aberrant conformers. Clear loss‐of‐function deletion mutations were identified in both alleles of 1 patient. Muscle histopahtology in this patient showed a striking inflammatory infiltrate of T cells and B cells. REexaminatin of biopys specimens from other laminin α2‐deficient patients showed minor signs of inflammation in each. Based on these findings and the histological and clinical picture suggesting failure of muscle regeneration, a pathogenesis model for this major subswt of congenital muscular dystrophy is proposed. Our data show that muscle histopatholgoy showing a neonatal inflammatory process shold be considered consistent with congenital muscular dystrophy.
Skew deviation following vestibular nerve surgery
Authors: Riordan‐Eva P. , Harcourt J. P. , Faldon M. , Brookes G. B. , Gresty M. A. 
Published: January 2005

AbstractEighteen consecutive patients undergoing vestibular nerve surgery underwent pre‐ and postoperative examination of ocular motility. Five patients developed a skew deviation following surgery, with the lower eye on the operated side and an incomitant pattern of deviation in all cases. Three patients experienced diplopia lasting from 1 day to 6 months. The magnitude of skew deviation was increased by head tilt away from the operated side in only 1 case. The development of skew deviation was not determined by preoperative ocular alignment or binocular function, or any particular type or pattern of vestibular disease. There was an association with large changes in ocular torsion and subjective visual vertical, which correlated with lesser degrees of canal paresis to preoperative caloric testing on the operated side. No patient developed a head tilt postoperatively. There is a gradation of responses to surgical vestibular deafferentation in humans, skew deviation only occurring in patients suffering marked changes in subjective visual vertical and ocular torsion.
Mitochondrial function in muscle from elderly athletes
Authors: Brierley Elizabeth J. , Johnson Margaret A. , Bowman Andrew , Ford Gary A. , Subhan Feisel , Reed James W. , James OliverF. W. , Turnbull Douglass M. 
Published: January 2005

AbstractThe extent to which mitochondria are involved in the aging process is conttroversial; much of the reported decline in mitochondrial oxidations in human skeletal muscle may be due to disease and inactivity rather than age. To study true aging, mitochondrial respiratory chain function was studied in 9 young and 12 elderly athletes. No significant deterioration with age was observed. If mitochondria are involved in aging, it must be through a more subtle mechanism than a global decline in respiratory chain activity.
Maternal inheritance in Parkinson's disease
Authors: Wooten G. Frederick , Currie Lillian J. , Bennett James P. , Harrison Madaline B. , Trugman Joel M. , Parker W. Davis 
Published: January 2005

AbstractTo evaluate possible matrilineal factors in the inheritance of Parkinson's disease, we prospectively identified families in which a parent and multiple siblings had Parkinson's disease. In each of the 5 families identified, the affected parent was the mother (p < 0.03). The age at onset in the offspring generation in these 5 families was younger than the age at onset in the parental generation (p < 0.001). In addition, the age at onset in all patients with an affected mother (n = 18) was younger than the age at onset in the affected mothers (p > 0.001). No difference was found between the age at onset in patients with an affected father (n = 14) and the age at onset in the affected fathers. These results are consistent with a role for inherited abnormalities of mitochondrial DNA in the pathogenesis of at least some cases of Parkinson's disease.
Plasma Levels of amyloid β proteins Aβ1–40 and Aβ1–42(43) are elevated in Down's syndrome
Authors: Tokuda Takahiko , Fukushima Tetsuro , Ikeda Shu‐Ich , Sekijima Yoshiki , Shoji Shin'Ichi , Yanagisawa Nobuo , Tamaoka Akira 
Published: January 2005

AbstractTo investigate the effect of the overexpression of β‐amyloid precursor protein (APP) on the production of two major amyloid β protein (Aβ) species, Aβ40 and Aβ42(43), we measured amounts of Aβ1–40 and Aβ1–42(43) in the plasma from 44 patients with Down's syndrome (DS) (age, 19–61 years) and 66 age‐matched normal controls using enzyme‐linked immunosorbent assays. Plasma concentrations of both Aβ1–40 and Aβ1–42(43) were increased about 3‐fold and 2‐fold, respectively, in DS patients compared with normal controls. Especially, the increases in plasma Aβ1–40 in DS Patients were statistically higher than the 1.5‐fold increase one might predict based on the gene dose of APP in DS. These findings showed that both Aβ1–40 and Aβ1–42(43) are increased in plasma in DS patients, the former more than the latter, suggesting that overexpression of APP and/or other genes may have different effects on the production of these two Aβ species in DS.
Pathological correlates of extrapyramidal signs in Alzheimer's disease
Authors: Liu Yan , Stern Yaakov , Chun Michael R. , Jacobs Diane M. , Yau Patricia , Goldman James E. 
Published: January 2005

AbstractExtrapyramidal signs frequently accompany Alzheimer's disease (AD), but the pathological substrate remains unknown. Clinical and postmortem information from patients with AD, Parkinson's disease, or progressive supranuclear palsy and control subjects seen at a large tertiary medical center between 1989 and 1994 was examined. AD patients who had taken neuroleptics and AD brains that also contained Lewy bodies were excluded. The presence of extrapyramidal signs was determined using the Unified Parkinson's Disease Rating Scale. Sections of basal ganglia, subthalamic nucleus, and substantia nigra were examined for neurofibrillary tangles and neuropil threads and the nigra for neuronal numbers. Patients with AD (with or without extrapyramidal signs) did not show neuronal loss in the nigra compared to control subjects, while both Parkinson's disease and progressive supranuclear palsy brains showed marked depletion. The number of neurofibrillary tangles and neuropil threads was increased in AD (with or without extrapyramidal signs) nigra compared to control tissue, and also in progressive supranuclear palsy nigra, but not Parkinson's disease nigra. The numbers of nigral neurofibrillary tangles and neuropil threads were positively related to extrapyramidal signs in AD. There were no correlations between tangles and threads in the basal ganglia or subthalamic nucleus and extrapyramidal signs in AD. Thus, extrapyramidal signs in AD correlate best with tangle pathology in the nigra and do not require the concomitant presence of Lewy bodies.