bluuebunny/crossref_metadata_2025_split huggingface dataset:
Leber's hereditary optic neuropathy plus dystonia is caused by a mitochondrial DNA point mutation
Authors: Shoffner John M. , Brown Michael D. , Stugard Carol , June Albert S. , Pollock Stephen , Haas Richard H. , Kaufman Allan , Koontz Deborah , Kim Yoon , Graham Jennifer R. , Smith Edwin , Dixon John , Wallace Douglas C. 
Published: January 2005

AbstractA Novemberel point mutation in the ND6 subunit of complex I at position 14,459 of the mitochondrial DNA (MTND6*LDY T14459A) was identified as a candidate mutation for the highly tissue‐specific disease. Leber's hereditary optic neuropathy plus dystonia. Since the MTND6*LDYT14459A mutation was identified in a single family, other pedigrees with the mutation are needed to confirm its association with the disease. Clinical, biochemical, and genetic characterization is reported in two additional pedigress. Leber's hereditary optic neuropathy developed in two family members in one pedigree. The dAugusthter had clinically silent basal ganglia lesions. In a second pedigree, a single individual presented with childhood‐onset generalized dystonia and bilateral basal ganglia lesions. Patient groups that included individuals with Leigh's disease, dystonia plus complex neurodegeneration, and Leber's hereditary optic neuropathy did not harbor the MTND6*LDYT14459A mutation, suggesting that this mutation displays a high degree of tissue specificity, thus producing a narrow phenotypic range. These results confirm the association of the MTND6*LDYT14459A mutation with Leber's herediatary optic neuropathy and/or dystonia. As the first genetic abnormality that has been identified to cause generalized dystonia, this mutation suggests that nuclear DNA or mitochondrial DNA mutations in oxidative phosphorylation genes are important considerations in the pathogenesis of dystonia.
Leptomeningeal tumor in primarchy central nervous system lymphoma: Recognition, significance, and implications
Authors: Balmaceda Casilda , Gaynor Jeffrey J. , Sun Ming , Gluck Jose Torres , DeAngelis Lisa M. 
Published: January 2005

AbstractThe true incidence of leptomeningeal tumor in priMarchy central nervous system lymphoma is unknown. We studied prospectively the cerebrospinal fluid profile of 96 patients without acquired immunodeficiency syndrome but with priMarchy central nervous system lymphoma at diagnosis, at completion of treatment, and at recurrence. Magnetic resonance images and pathology slides were examined for evidence of leptomeningeal tumor. Leptomeningeal tumor was diagnosed by (1) positive findings on cerebrospinal fluid cytology, (2) leptomeningeal or subependymal enhancement on magnetic resonance imaging, or (3) pathological evidence of leptomeningeal tumor. We recorded whether treatment directed against the leptomeninges was given. Cerebrospinal fluid was examined in 86 of 96 patients at diagnosis and 29 of 42 at recurrence. The incidence of leptomeningeal tumor was 42% at diagnosis and 41% at recurrence. Only elevated levels of protein and lactate dehydrogenase isoenzyme‐5 were significantly associated with leptomeningeal tumor (r= 0.012,p= 0.016, respectively). Treatment against the leptomeninges was significantly associated with the probability of achieving a complete response and a longer freedom from relapse. Patients older than 50 years had a worse disease‐specific survival but a similar probability of responding to therapy as younger patients. Our data show that leptomeningeal tumor in priMarchy central nervous system lymphoma is more prevalent than originally thought, and indicate the need for therapy inclusive of the leptomeninges in all patients.
Aging, energy, and oxidative stress in neurodegenerative diseases
Authors: Beal M. Flint 
Published: January 2005

AbstractThe etiology of neurodegenerative diseases remains enigmatic; however, evidence for defects in energy metabolism, excitotoxicity, and for oxidative damage is increasingly compelling. It is likely that there is a complex interplay between these mechanisms. A defect in energy metabolism may lead to neuronal depolarization, activation of N‐methyl‐D‐aspartate excitatory amino acid‐receptors, and increases in intracellular calcium, which are buffered by mitochondria. Mitochondria are the major intracellular source of free radicals, and increased mitochondrial calcium concentrations enhance free radical generation. Mitochondrial DNA is particularly susceptible to oxidative stress, and there is evidence of age‐dependent damage and deterioration of respiratory enzyme activities with normal aging. This may contribute to the delayed onset and age dependence of neurodegenerative diseases. There is evidence for increased oxidative damage to macromolecules in amyotrophic lateral sclerosis, Huntington's disease, Parkinson's disease, and Alzheimer's disease. Potential therapeutic approaches include glutamate release inhibitors, excitatory amino acid antagonists, strategies to improve mitochondrial function, free radical scavengers, and trophic factors. All of these approaches appear promising in experimental studies and are now being applied to human studies.
A Greek‐American kindred with autosomal dominant, levodopa‐responsive parkinsonism and anticipation
Authors: Markopoulou K. , Wszolek Z. K. , Pfeiffer R. F. 
Published: January 2005

AbstractInterest is increasing concerning the role of genetic factors in the etiology of Parkinson's disease. We report the analysis of a Greek‐American kindred with levodopa‐responsive parkinsonism. Of the 98 individuals present in six generations of this pedigree, 16 individuals in three successive generations have developed parkinsonism. Affected members were examined both in Greece and in the United States. The clinical presentation consisted of asymmetric rigidity, resting tremor, bradykinesia, and postural instability, and symptoms were responsive to levodopa. The disease appears to be inherited in an autosomal dominant manner. The inheritance pattern and the development of parkinsonism in successive generations on two continents challenges environmental factors as the primary cause in the pathogenesis of parkinsonism in this kindred. Anticipation is present in this pedigree. The affected members in the third generation developed symptoms at ages 50 to 71, in the fourth at ages 40 to 55, and in the fifth at age 31 years. This is another example of a neurodegenerative disease with autosomal dominant inheritance and anticipation. A molecular genetic analysis of this pedigree is in progress.
Bilateral fetal nigral transplantation into the postcommissural putamen in Parkinson's disease
Authors: Freeman Thomas B. , Olanow C. Warren , Hauser Robert A. , Nauert G. Michael , Smith Donald A. , Borlongan Cesario V. , Sanberg Paul R. , Holt Douglas A. , Kordower Jeffrey H. , Vingerhoets Francois J. G. , Snow Barry J. , Calne Donald , Gauger Lisa L. 
Published: January 2005

AbstractWe performed fetal nigral transplantations in 4 Parkinson's disease (PD) patients. Solid grafts were bilaterally implanted into the postcommissural putamen using 3 to 4 donors per side aged 6 1/2 to 9 weeks postconception. Transplant deposits were separated by no more than 5 mm in three dimensions. Cyclosporine was employed for a total of 6 months. Patients were evaluated at baseline and at 1, 3, and 6 months postoperatively. Striatal 18‐fluorodopa uptake was assessed by positron emission tomography at baseline and at 6 months postoperatively. The procedure was well tolerated in all patients. One patient had a clinically asymptomatic superficial cortical hemorrhage along the needle tract and a second had transient postoperative confusion and hallucinations. All patients experienced clinically meaningful benefit. Significant improvement (p < 0.05) was detected in total UPDRS score during the „off”︁ state, Schwab‐England disability score during the „off”︁ state, percent „off”︁ time, and percent „on”︁ time with dyskinesia. Increased striatal fluorodopa uptake was observed bilaterally in each patient, with mean increases of 53% on the right (p = 0.01) and 33% on the left (p = 0.08). Our study demonstrated clear and consistent improvement in clinical features and striatal fluorodopa uptake following fetal tissue transplantation in patients with advanced PD whose condition was not improved preoperatively by drug manipulation. These preliminary results are encouraging and support further studies to evaluate grafting strategies as a therapy for PD.
Distinction between peroxisomal bifunctional enzyme and acyl‐CoA oxidase deficiencies
Authors: Watkins Paul A. , McGuinness Martina C. , Raymond Gerald V. , Hicks Beth A. , Sisk Jeanne M. , Moser Ann B. , Moser Hugo W. 
Published: January 2005

AbstractThe clinical distinction between patients with a disorder of peroxisome assembly (e.g., Zellweger syndrome) and those with a defect in a peroxisomal fatty acid β‐oxidation enzyme can be difficult. We studied 29 patients suspected of belonging to the latter group. Using complementation analysis, 24 were found to be deficient in enoylcoenzyme A hydratase/3‐hydroxyacylcoenzyme A dehydrogenase bifunctiona enzyme and 5 were deficient in acyl‐CoA oxidase. Elevated plasma very long‐chain fatty acids (VLCFA), impaired fibroblast VLCFA β‐oxidation, decreased fibroblast phytanic acid oxidation, normal plasmalogen synthesis, normal plasma l‐pipecolic acid level, and normal subcellular catalase distribution were characteristic findings in both disorders. The elevation in plasma VLCFA levels and impairment in fibroblast VLCFA β‐oxidation were more severe in bifunctional‐deficient than in oxidase‐deficient patients. The clinical course in bifunctional deficiency (profound hypotonia, neonatal seizures, dysmorphic features, age at death ∼9 months) was more severe than in oxidase deficiency (moderate hypotonia without dysmorphic features, development of a leukodystrophy, age at death ∼4 yr). Based on these findings, accurate early diagnosis of these deficiencies of peroxisomal β‐oxidation enzymes is possible.
Immunocytochemical quantitation of human immunodeficiency virus in the brain: Correlations with dementia
Authors: Glass Jonathan D. , Fedor Helen , Wesselingh Steven L. , McArthur Justin C. 
Published: January 2005

AbstractThe pathogenesis of human immunodeficiency virus (HIV)‐associated dementia is unclear, and the underlying pathological substrate has been a matter of debate. In a prospectively clinically characterized population of acquired immunodeficiency syndrome (AIDS) patients we investigated the relationship between the clinical syndrome of HIV‐associated dementia and the presence and relative quantity of immunocytochemical Marchkers for HIV‐1 (gp41 antibody), and for macrophages and microglia (HAM‐56 antibody). Sections from the basal ganglia and frontal lobes from the brains of 51 patients were studied, and the data were stratified for severity of dementia (16 nondemented, 12 mildly demented, 23 severely demented), rate of dementia progression, duration of AIDS, use of antiretrovirals, and several other demographic features. We found a highly significant correlation between the degree of macrophage staining and the severity of dementia but only a borderline correlation between the presence and amount of gp41‐positive cells and dementia. Several nondemented patients showed abundant gp41 immunoreactivity, and some severely demented showed little to no gp41 immunoreactivity. Other correlations with the immunostaining data, including antiretroviral use, were not significant. We conclude that the presence of macrophages and microglia is a better correlate with HIV‐associated dementia than is the presence and amount of HIV‐infected cells in the brain. These data support the concept that the pathogenesis of HIV‐associated dementia is likely due to indirect effects of HIV‐infection of the brain, possibly through the actions of macrophages and microglia.
Monocyte/macrophage differentiation in early multiple sclerosis lesions
Authors: Brück Wolfgang , Porada Phyllis , Poser Sigrid , Rieckmann Peter , Hanefeld Folker , Kretzschmarch Hans A. , Lassmann Hans 
Published: January 2005

AbstractMonocyte/macrophage differentiation was studied in biopsy samples of multiple sclerosis (MS) lesions obtained in the early course of the disease. Macrophages were identified by immunocytochemistry using a panel of antibodies recognizing different macrophage‐activation antigens. The number of cells stained with each antibody was related to the demyelinating activity of the lesions as detected by the presence of myelin degradation products. The pan‐macrophage Marchker Ki‐M1P revealed the highest numbers of macrophages in early and late active lesions. Lower numbers were encountered in inactive, demyelinated, or remyelinated lesions. The acute stage inflammatory macrophage Marchkers MRP14 and 27E10 were expressed in either only early active (MRP14) or early and late active (27E10) lesions, thus allowing the identification of actively demyelinating lesions. The chronic stage inflammatory macrophage Marchker 25F9, in contrast, showed increasing expression with decreasing lesional activity. These findings indicate a differentiated pattern of macrophage activation in MS lesions and allow the staging of demyelinating lesions in routinely fixed and paraffin‐embedded tissue.
Anti‐ganglioside GM1 antibodies in guillain‐barré syndrome and their relationship to Campylobacter jejuni infection
Authors: Rees Jeremy H. , Gregson Norman A. , Hughes Richard A. C. 
Published: January 2005

AbstractTo clarify the association between Campylobacter jejunei (Cj) infection and antibodies to ganglioside GM1 (anti‐GM1) in Guillain‐Barré syndrome (GBS), we have carried out a prospective case‐control study of 96 patients with GBS. Cj infection occurred in 25 (26%) patients. IgG and/or IgM anti‐GM1 were identified in 24 (25%) patients and in 1 of 71 (1.4%) household controls (p < 0.001). Thirteen of the 25 (52%) Cj‐postive patients had anti‐GM1 compared with 11 of the 71 (15%) Cj‐negative patients (p < 0.001). Neither the peak overall disability nor the 1‐year disability differed between the anti‐GM1‐positive and anti‐GM1‐negative patients. However, patients with the combimation of Cj infection and anti‐GM1 positivity recovered more slowly than Cj/anti‐GM1‐negative patients (p = 0.05), were more likely to have axonal degeneration, and were significantly more disabled at the end of 1 year (p = 0.02). The presence of Cj infection is more important than anti‐GM1 postivity in determining the extent of axonal involvement and, hence, prognosis. Since the presence of anti‐GM1 is not a significant poor‐prognostic factor, a search should be made for other properties of Cj infection that would account for its relationship to axonal degeneration.
Neurological sequelae of cyanide intoxication — the patterns of clinical, magnetic resonance imaging, and positron emission tomography findings
Authors: Rosenow F. , Herholz K. , Lanfermann H. , Weuthen G. , Ebner R. , Kessler J. , Ghaemi M. , Heiss W.‐D. 
Published: January 2005

AbstractWe report 2 patients with neurological sequelae of oral cyanide intoxication who were evaluated clinically and neuropsychologically, with high‐resolution magnetic resonance imaging and one of them with positron emission tomography. The clinical syndrome was characterized by extrapyramidal motor and cerebellar symptoms such as bradykinesia, hypomimia, slowed speech, anteropulsion, and Marchked retropulsion, but little tremor. The sensory and pyramidal motor systems were normal or relatively spared. On neuropsychological testing the intellectual capacity and memory functions were normal, whereas the speed of motor reaction and verbal fluency were reduced. Magnetic resonance imaging showed damage of the globus pallidus, putamen, substantia nigra, subthalamic nucleus, and cerebellum in both patients, whereas the sensory‐motor cortex and hippocampus were relatively spared. 18F‐6‐Fluoro‐dopa positron emission tomography revealed a symmetrical reduction of striatal dopa uptake by 42% on average that was similar in the putamen and caudate. 18F‐2‐Fluoro‐2‐deoxyglucose positron emission tomography showed a regional reduction of the glucose metabolism in the posterior putamen and temporo‐parieto‐occipital and cerebellar cortex.
Neural apoptosis
Authors: Bredesen Dale E. 
Published: January 2005

AbstractApoptosis is a mode of cell death in which the cell plays an active role in its own demise. The study of neural apoptosis, the identification of genes controlling apoptosis, and the examination of the mechanisms by which these genes achieve their effects have assumed increasing importance over the past few years. This is because (1) neural apoptosis occurs not only in development, but also in pathophysiological states such as stroke, glutamate toxicity, and β‐amyloid peptide toxicity; (2) genes that control apoptotic cell death, such asbcl‐2, p35, p53, andp75NTR, also modulate necrotic neural death in some cases; (3) the emerging mechanisms by which these genes control apoptosis may be relevant for understanding neurodegenerative processes, and for the design of therapeutic agents; and (4) the findings that the cell plays an active role in its own demise, and that specific gene products are involved, suggest that therapeutic intervention may be feasible.
Neuromuscular effects of papuan taipan snake venom
Authors: Connolly S. , Trevett A. J. , Nwokolo N. C. , Lalloo D. G. , Naraqi S. , Mantle D. , Schofield I. S. , Fawcett P. R. W. , Harris J. B. , Warrell D. A. 
Published: January 2005

AbstractSnakebite is a cause of significant morbidity in Central Province, Papua New Guinea. Three adult patients with clinical evidence of neurotoxicity following envenomation by the Papuan taipan had serial neurophysiological examinations over the course of their subsequent hospitalization. All required artificial ventilation for 2.5 to 5 days. The compound muscle action potential (CMAP) amplitudes declined over the first 2 to 4 days after envenoming and then gradually increased in parallel with clinical recovery. Repetitive stimulation studies revealed a distinctive pattern of abnormality. Activation resulted in brief potentiation of the CMAP followed by significantly greater decrement than observed at rest. This effect lasted up to 30 minutes and was not altered after intravenous edrophonium. Single‐fiber electromyographic recordings during the recovery phase of the illness were abnormal with marked blocking and increased jitter. All patients were able to return home.
Acute optic neuritis: Myelin basic protein and proteolipid protein antibodies, affinity, and the HLA system
Authors: Sellebjerg F. , Madsen H. O. , Frederiksen J. L. , Ryder L. P. , Svejgaard A. 
Published: January 2005

AbstractAnti—myelin basic protein, anti—proteolipid protein, and anti—myelin basic protein peptide (amino acid residues 1–20, 63–88, and 89–101) antibody—secreting cells were studied in 20 patients with idiopathic optic neuritis, 20 with optic neuritis as part of multiple sclerosis, and 20 neurological control subjects. Antibody‐secreting cells were enumerated with an immunospot assay; the relative binding affinity of the antibodies was estimated by elution with thiocyanate. Patients with optic neuritis had more anti—myelin basic protein and anti—proteolipid protein antibodies than did control subjects (both p < 0.05); there was no difference between idiopathic optic neuritis and optic neuritis as a symptom of multiple sclerosis. Presence of the multiple sclerosis—associated DRB1 1501 gene was not associated with preferential synthesis of high‐affinity antibodies reactive with a single myelin basic protein peptide or with preferential synthesis of either anti—myelin basic protein or anti—proteolipid protein antibodies. The results demonstrate a potential for intrathecal synthesis of both anti—myelin basic protein and anti—proteolipid protein antibodies of high apparent affinity in patients with optic neuritis.
Guidelines for the use of magnetic resonance techniques in monitoring the treatment of multiple sclerosis
Authors: Miller D. H. , Albert P. S. , Barkhof F. , Francis G. , Frank J. A. , Hodgkinson S. , Lublin F. D. , Paty D. W. , Reingold S. C. , Simon J. 
Published: January 2005

AbstractBecause of the major difficulties in measuring clinical end points in multiple sclerosis (MS) treatment trials, there has been much enthusiasm for using magnetic resonance imaging (MRI) findings as an alternative outcome. To provide international consensus guidelines for the use of MRI in MS clinical trials, a task force of the US National MS Society was convened. The recommendations of the task force are presented in this review. Given the high sensitivity for detecting pathological activity in relapsing‐remitting and secondary progressive MS, monthly T2‐weighted and gadoliniumenhanced brain MRI is an excellent tool for short‐term exploratory trials of new agents where it serves as the primary end point; in particular, failure to demonstrate a reduction in lesion activity avoids the time, cost, and risks of a larger clinical end point study. However, conventional MRI findings have a limited correlation with disability in established MS. The primary end point of a definitive trial should therefore be clinical, although serial MRI at 6‐ to 12‐month intervals is a useful secondary end point in providing an index of pathological progression. In trials of patients presenting with clinically isolated syndromes suggestive of MS, MRI findings can be used in the entry criteria, and as a secondary outcome measure, but conversion to clinically definite MS should be the primary outcome. The pathological substrates of irreversible disability are demyelination and axonal loss. Putative magnetic resonance markers for these processes include decreased N‐acetylaspartate on proton magnetic resonance spectroscopy, decreased magnetization transfer ratios, hypointensity on T1‐weighted images, and loss of short T2 water fractions, some of which relate more closely to disability than conventional MRI findings. Further technical developments should lead to more accurate quantitation, greater pathological specificity, and stronger clinical correlations.
Dietary lipids and antioxidants in Parkinson's disease: A population‐based, case‐control study
Authors: Logroscino Giancarlo , Marder Karen , Cote Lucien , Tang Ming‐Xin , Shea Steven , Mayeux Richard 
Published: January 2005

AbstractOxidative stress plays an important role in the pathogenesis of Parkinson's disease (PD). In a population‐based, case‐control study we examined whether dietary intake of antioxidants and other oxidative compounds was associated with PD. Dietary intake was assessed by a semiquantitative food‐frequency questionnaire in 110 PD case patients and 287 control subjects. A higher caloric intake was observed in patients with PD and did not vary with increasing duration of symptoms. Energy‐adjusted fat intake was significantly higher among patients with PD than control subjects (p for trend = 0.007). Intake of protein (p for trend = 0.17) and carbohydrates (p for trend = 0.46) did not differ in patients and control subjects. Analyses of the primary sources of fat indicated that increasing intake of animal fats was strongly related to PD (odds ratio, 5.3; 95% confidence interval, 1.8–15.5; p for trend = 0.001). No significant differences were observed for intake of vitamins with antioxidant activity. An increase in the consumption of animal fats among patients with PD is consistent with the hypothesis that oxidative stress and lipid peroxidation are important in the pathogenesis of this disease. No effect of vitamins with antioxidant activity, either from food or supplements, was observed.