bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hypertension in the elderly is associated with white matter lesions and cognitive decline
Authors: van Swieten J. C. , Geyskes G. G. , Derix M. M. A. , Peeck B. M. , Ramos L. M. P. , van Latum J. C. , van Gijn J. 
Published: January 2005

AbstractForty‐two elderly patients (mean age, 66.2 ± 5.1 yr) with hypertension, treated for an average of 17.3 years (standard deviation, 10.3), and 42 control subjects (mean age, 66.5 ± 4.8yr), matched for age, sex, and level of education, were studied with regard to the detection of lesions in the cerebral white matter with magnetic resonance imaging (MRI), particularly with axial T2‐weighted images. The assessment of the MRI scans was blinded. Ten hypertensive patients showed confluent lesions in the white matter, versus only 1 control subject (Chi‐square test, p = 0.01). The presence of diffuse lesions of the white matter was related to age but not to the known duration of hypertension, nor to the presence of any other cardiovascular risk factors. Cognitive function was measured in 34 hypertensive patients and in 18 control subjects. Results of the Mini‐Mental State Examination, the Stroop color‐word test, Trailmaking test, and the visual subtest of the Wechsler Memory scale were worse in patients with confluent lesions of the white matter; there was no difference in mental functioning between hypertensive patients and control subjects with normal white matter or with only small focal lesions. Our findings suggest that long‐standing hypertension in some patients may cause not only strokes but also chronic end‐organ damage in the form of demyelination of the white matter, with cognitive decline.
Human nerve growth factor prevents degeneration of basal forebrain cholinergic neurons in primates
Authors: Koliatsos Vassilis E. , Clatterbuck Richard E. , Nauta Haring J. W. , Knüsel Beat , Burton Louis E. , Hefti Franz F. , Mobley William C , Price Donald L. 
Published: January 2005

AbstractBasal forebrain cholinergic neurons respond to nerve growth factor (NGF), and it has been suggested that the administration of NGF might prevent their degereration in patients with Alzheimer's disease. One major prerequisite to be fulfilled before the consideration of clinical trials of NGF in patients with Alzheimer's disease is the demonstration that human NGF affects basal forebrain cholinergic neurons in primates. In the present study, we used a recombunant human nerve growth facotr (rhNGF), which we previousl showed to be active on rat basa forebrain cholinergic neurons, in nonhuman primates with a unilateral transection of the fornix (a well‐established model for the induction of retrograde degenerative changes in septal cholinergic neurons). After the lesion, one group of animals received rhNGF and a second group received vehicle solution for 2 weeks. In animals receiving vehicle, the medical septal nucleus ipsilateral to the lesion showed reductions in numbers (55°) and size of cell bodies immunoreactive for NGF receptor and choline acetyltransferase. In Sissl stains, many cells showed frduced size and basophilia. The rhNGF completely prevented alternation in the number and size of NGF receptor—and choline acetyltransferase—immunnoreactive neurons in the medical septal nucles and reversed atrophy in a subpopulation of large, basophilic medical which we have previously used in the same primate lesion paradigm. The restoration of the phenotype of injured acetylcholine‐dependent memory impariments that occur in aged nonhuman primates. In concert, results of the present investigation provide critical information for the futrue use of NGF in in patients with neurological disorders that affect NGF‐responsive cells in the peripherl and central nervous system.
Sensorimotor disinhibition in Parkinson's disease: Effects of levodopa
Authors: Caligiuri Michael P. , Heindel William C. , Lohr James B. 
Published: January 2005

AbstractIt has been known for some time that patients with Parkinson's disease (PD) have difficulty executing simultaneous motor acts, yet the pathophysiology underlying this impairment remains uncertain. We examined the possibility that these dual‐task deficits stem from defective sensorimotor mechanisms producing interference between the motor programs underlying the two tasks. Patients with PD and normal control subjects were tested on their ability to maintain steady‐state force with one hand while performing a force–reaction time task with the other hand. Although performance was worse on the dual‐task than on the single‐task condition for both subject groups, only the patients with PD demonstrated significant interference between the two tasks. The interference across tasks improved in 87% of the patients with PD when tested after treatment with carbidopa/levodopa (Sinemet). These findings support the contention that, in patients with PD, disturbances in the execution of simultaneous motor performance may be due to sensorimotor disinhibition.
Lethal cytomegalovirus infection in preterm infants: Clinical, radiological, and neuropathological findings
Authors: Perlman Jeffrey M. , Argyle Craig 
Published: January 2005

AbstractFifteen premature infants with lethal congenital cytomegalovirus infection were studied to determine the clinical, neuroradiological, and neuropathological characteristics of the disease in this population. Nine infants were liveborn but died at a postnatal age of 18 ± 21 days; 6 infants were stillborn. Clinical findings in liveborn infants included microcephaly (77%), seizures (55%), hypotonia (33%), and multiple contractures (18%). Ophthalmological findings included chorioretinitis, optic atrophy, and corneal opacities. Neuroradiological findings included the postnatal evolution of periventricular calcification in 1 infant, and cerebellar hypoplasia diagnosed by magnetic resonance imaging in 1 infant. Neuropathological findings included periventricular necrosis and calcification (12), associated diffuse calcification frequently involving the convexity of the gyri (6), cerebellar hypoplasia (5), periventricular leukomalacia (2), intraventricular hemorrhage (2), hydrocephalus (2), and porencephalic cyst (1). Intranuclear inclusion bodies within the brain were observed in 4 infants, whereas systemic inclusion bodies were present in all infants. These data indicate several atypical findings in preterm infants rarely reported in term infants, including hypotonia, multiple contractures, periventricular leukomalacia, and optic atrophy.
Osmolality and nonsynaptic epileptiform bursts in rat CA1 and dentate gyrus
Authors: Roper Steven N. , Obenaus Andre , Dudek F. Edward 
Published: January 2005

AbstractIn several clinical situations, such as hyposmolar states and hypoxia‐ischemia, reductions in the size of the extracellular space are associated with increased seizure susceptibility. Nonsynaptic interactions provide a likely means of mediating the effect of extracellular space on seizure susceptibility. Synchronous bursting of CA1 hippocampal neurons occurs via nonsynaptic mechanisms in solutions containing very low {Ca2+} and excitatory amino acid antagonists. We tested the hypothesis that lowering the osmolality of the extracellular medium could induce nonsynaptic bursting in the dentate gyrus, even though it is normally resistant to this treatment. Extracellular field potentials were recorded in the dentate gyrus and CA1 area of rat hippocampal slices. In the low‐{Ca2+} solution with normal osmolality, bursts of population spikes were recorded from the dentate gyrus in only 7% of the slices, but solutions with decreased osmolality induced bursting in 63%. Corresponding values for the CA1 area were 60 and 73%, respectively. Mannitol, which reversed the hyposmolar state, abolished bursting in both regions. This study demonstrates that reducing the size of the extracellular space by lowering extracellular osmolality can transform a seizure‐resistant area into one that exhibits robust epileptiform activity.
Contrasting effects of alpha, beta, and gamma interferons on nonspecific suppressor function in multiple sclerosis
Authors: Noronha Avertano , Toscas Angela , Jensen Mark A. 
Published: January 2005

AbstractInterferons are biological molecules with antiviral, antiproliferative, and immunomodulatory actions. Interferon alpha (IFN‐α) and ‐β are potentially useful in the treatment of multiple sclerosis (MS). IFN‐γ, in contrast, increases the frequency of exacerbations of MS. In this study, we compared the effect of recombinant human IFN‐α, ‐β, and ‐γ on suppressor function in patients with MS. Nonspecific suppressor cell function, measured in a concanavalin A suppressor assay, was significantly decreased in 16 patients with progressive MS (mean percent suppression ± SEM, 14.4 ± 5.5 in patients with MS, 33.5 ± 4.8 in 16 normal subjects; p < 0.001). Recombinant human IFN‐β augmented suppressor function in MS to 45.4 ± 5.1% (p < 0.001) and in control subjects to 56.8 ± 3.8% (p < 0.001). Similarly, recombinant human IFN‐α improved suppression in MS to 43.0 ± 5.6% (p < 0.001) and in control subjects to 51.1 ± 5.9% (p < 0.001). In contrast, recombinant human IFN‐γ had no effect on suppressor function in patients with MS and in control subjects. This study shows that IFN‐α and ‐β augment deficient suppressor function in MS, whereas IFN‐γ has no effect on suppressor function in the progressive phase of the disease.
Does impairment of energy metabolism result in excitotoxic neuronal death in neurodegenerative illnesses?
Authors: Beal M. Flint 
Published: January 2005

AbstractThe etiology of nerve cell death in neuronal degenerative diseases is unknown, but it has been hypothesized that excitotoxic mechanisms may play a role. Such mechanisms may play a role in diseases such as Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis, and Alzheimer's disease. In these illnesses, the slowly evolving neuronal death is unlikely to be due to a sudden release of glutamate, such as occurs in ischemia. One possibility, however, is that a defect in mitochondrial energy metabolism could secondarily lead to slow excitotoxic neuronal death, by making neurons more vulnerable to endogenous glutamate. With reduced oxidative metabolism and partial cell membrane depolarization, voltage‐dependent N‐methyl‐D‐apartate (NMDA) receptor ion channels would be more easily activated. In addition, several other processes involved in buffering intracellular calcium may be impaired. Recent studies in experimental animals showed that mitochondrial toxins can result in a pattern of neuronal degeneration closely resembling that seen in Huntington's disease, which can be blocked with NMDA antagonists. NMDA antagonists also block neuronal degeneration induced by 1‐methyl‐4‐phenylpyridium, which has been implicated in experimental models of Parkinson's disease. The delayed onset of neurodegenerative illnesses could be related to the progressive impairment of mitochondrial oxidative phosphorylation, which accompanies normal aging. If defective mitochondrial energy metabolism plays a role in cell death in neurodegenerative disorders, potential therapeutic strategies would be to use excitatory amino acid antagonists or agents to bypass bioenergetic defects.
Transplantation of fetal dopamine neurons in Parkinson's disease: PET {18F}6‐L‐fluorodopa studies in two patients with putaminal implants
Authors: Sawle Guy V. , Bloomfield Peter M. , Ourklund Anders Bj , Brooks David J. , Brundin Patrik , Leenders Klaus L. , Lindvall Olle , Marsden C. David , Rehncrona Stig , Widner Håkan , Frackowiak Richard S. J. 
Published: January 2005

AbstractTwo patients with Parkinson's disease who underwent implantation of fetal mesencephalic tissue into the putamen were serially studied using positron emission tomography and {18F}6‐L‐fluorodopa ({18F}dopa). The uptake of {18F}dopa is related to the functional integrity of the presynaptic dopaminergic system. Preoperative studies revealed a marked decrease in putamen {18F}dopa uptake, with lesser involvement of the caudate. Two and 4 months, respectively, after operation, both patients demonstrated functional improvement, as described elsewhere. One patient was scanned 5, 8, and 13 months after the operation and the other was scanned 7 and 12 months after the operation. In both patients, {18F}dopa uptake increased within the operated putamen despite a progressive decrease in tracer uptake in the unoperated striatal structures. We believe that this increased uptake of {18F}dopa at the implantation site represents functional integrity within a surviving neural graft. While there has been little further clinical improvement beyond the fifth postoperative month, the uptake of {18F}dopa at the operation site in both patients has progressively increased. The kinetic data provide evidence of disease progression in the unoperated striatum, which balanced against increasing graft function, may explain why clinical improvement reached a plateau within months after surgery.
1H and 31P magnetic resonance spectroscopy of the brain in degenerative cerebral disorders
Authors: van der Knaap Marjo S. , van der Grond Jeroen , Luyten Peter R. , Den Hollander Jan A. , Nauta Jos J. P. , Valk Jaap 
Published: January 2005

AbstractProton and phosphorus magnetic resonance spectroscopy of the brain was performed in 35 patients with degenerative cerebral disorders: 24 patients had demyelinating (white matter) disorders and 11 patients had neuronal (gray matter) disorders. Four grades of demyelination and three grades of cerebral atrophy were distinguished by magnetic resonance imaging criteria. The spectroscopic data were compared with normal values previously obtained. With increasing degrees of demyelination, lower ratios of phosphodiesters to β‐ATP were found. This trend was statistically significant. Decreased phosphodiester–β‐ATP ratios occurred simultaneously with imaging abnormalities. The decrease in phosphodiester–β‐ATP ratio in demyelinated areas is attributed to white matter rarefaction. Increasing cerebral atrophy was accompanied by lower ratios of N‐acetyl aspartate to creatine. This trend was statistically significant. The decrease in the N‐acetyl aspartate–creatine ratio was demonstrated before the magnetic resonance images showed signs of cerebral atrophy in patients with neuronal disorders. As N‐acetyl aspartate is located exclusively in neurons and their branches, a decrease of the N‐acetyl aspartate–creatine ratio can be attributed to neuronal and axonal damage and loss.
Mild senile dementia of the Alzheimer type. 4. Evaluation of intervention
Authors: Berg Leonard , Miller J. Philip , Baty Jack , Rubin Eugene H. , Morris John C. , Figiel Gary 
Published: January 2005

AbstractThe design of trials of interventions intended to slow or arrest the progression of senile dementia of the Alzheimer type must be based on analysis of the natural hisotry of the disease. Using a random coefficients statistical model, we analyzed the natural hisotry of senile dementia of the Alzheimer type in carefully defined subjects with milde disease (n = 68) for periods of up to 10 years. Subject performance was assessed longitudinally on batteries of clinical and psychometric measures. The characteristics of these measures were analyzed relevant to their utility as outcome measures for long‐term trials in patients with senile dementia of the Alzheimer type. Estimates were made of sample sizes required to show arrest, and 50% or 25% slowing in the progression of mild disease. We suggest that a clinically relevant global measure, such as the Sum of Boxes of the Clinical Dementia Rating scale, and a performance‐based clinical scale or psychometric measure would be appropriate in a 12‐ or 24‐month trial enrolling subjects with mild senile dementia of the Alzheimer type.
Late‐onset metachromatic leukodystrophy: Molecular pathology in two siblings
Authors: Kappler Joachim , von Figura Kurt , Gieselmann Volkmar 
Published: January 2005

AbstractWe report on a new allele at the arylsulfatase A (ARSA) locus causing late‐onset metachromatic leukodystrophy (MLD). In that allele arginine84, a residue that is highly conserved in the arylsulfatase gene family, is replaced by glutamine. In contrast to alleles that cause early‐onset MLD, the arginine84 to glutamine substitution is associated with some residual ARSA activity. A comparison of genotypes, ARSA activities, and clinical data on 4 individuals carrying the allele of 81 patients with MLD examined, further validates the concept that different degrees of residual ARSA activity are the basis of phenotypical variation in MLD.
Selective accumulation of aluminum and iron in the neurofibrillary tangles of Alzheimer's disease: A laser microprobe (LAMMA) study
Authors: Good Paul F. , Perl Daniel P. , Bierer Linda M. , Schmeidler James 
Published: January 2005

AbstractWe report the results of an examination of the elemental content of neurofibrillary tangle–bearing and neurofibrillary tangle–free neurons identified within the hippocampus of 10 subjects with Alzheimer's disease and 4 neuropathologically intact age‐matched control subjects. The study employed laser microprobe mass analysis (LAMMA), a technique that provides extremely sensitive multielement detection in plastic‐embedded, semithin‐sectioned tissues. Evidence for the selective accumulation of aluminum within the neurofibrillary tangle–bearing neurons was obtained in all 10 subjects with Alzheimer's disease. The site of aluminum deposition within these cells was the neurofibrillary tangle itself, and not the “nuclear region”, as we previously reported. Iron accumulation was also detected within neurofibrillary tangles. Evaluation for the accumulation of other elements within the tangle‐bearing neurons failed to reveal any other metallic element as being consistently present. In addition, probe sites directed to neurons identified in snapfrozen cryostat sections from 2 subjects with Alzheimer's disease revealed similar spectra with prominent aluminum‐related peaks, confirming that our findings are not related to exogenous contamination through fixation, embedding, or other procedures prior to analysis. This study further confirms the association of aluminum and neurofibrillary tangle formation in Alzheimer's disease.
Collagen cross‐linking of skin in patients with amyotrophic lateral sclerosis
Authors: Ono Seiitsu , Yamauchi Mitsuo 
Published: January 2005

AbstractCollagen cross‐links of skin tissue (left upper arm) from 11 patients with amyotrophic lateral sclerosis (ALS) and 9 age‐matched control subjects were quantified. It was found that patients with ALS had a significant reduction in the content of an age‐related, stable cross‐link, histidinohydroxylysinonorleucine, that was negatively correlated with the duration of illness. The contents of sodium borohydride–reducible labile cross‐links, dehydro‐hydroxylysinonorleucine and dehydro‐histidinohydroxymerodesmosine, were significantly increased and were positively associated with the duration of illness (r = 0.703, p < 0.05 and r = 0.684, p < 0.05, respectively). The results clearly indicate that during the course of ALS, the cross‐linking pathway of skin collagen runs counter to its normal aging, resulting in a “rejuvenation” phenomenon of skin collagen. Thus, cross‐linking of skin collagen is affected in ALS.
GM1 gangliosidosis in adults: Clinical and molecular analysis of 16 Japanese patients
Authors: Yoshida Kunihiro , Oshima Akihiro , Sakuraba Hitoshi , Nakano Takeshi , Yanagisawa Nobuo , Inui Koji , Okada Shintaro , Uyama Ei‐ichiro , Namba Reiko , Kondo Kiyohiko , Iwasaki Shin‐ichi , Takamiya Kiyoshi , Suzuki Yoshiyuki 
Published: January 2005

AbstractClinical findings were compared with the results of molecular analysis in 16 Japanes patients from 10 unrelated families with the adult/chronic form of GM1 gangliosidosis. Age of onset ranged from 3 to 30 years. Major clinical manifestations were gait and speech disturbances caused by persistent muscle hypertonia. Dystonic postures and movements, facial grimacing, and parkinsonian manifestations were commonly seen. Cerebellar signs, myoclonus, severe intellectual impairment, dysmorphism, or visceromegaly were not observed. A common single‐base substitution, 51Ile(ATC)→Thr(ACC), reported in a previous study of ours, was confirmed in 14 patients by the Bsu361 restriction site analysis; one was a compound heterozygote with another mutation (457Agr{CGA}→Gln{CAA}) and the others were homozygotes of this mutation. Clinically, the compound‐heterozygous patient showed more severe neurological manifestations and a more rapid clinical course than those of homozygotes. The homozygotes showed considerable variations in the age of onset and subsequent clinical course. The 51Ile→Thr mutant allele expressed a significant amount of β‐galactosidase activity, whereas the 457Arg→Gln mutant allele extremely low activity in human GM1 gangliosidosis fibroblasts. We conclude that these gene mutations causing different residual enzyme activities are related to the severity of clinical manifestations, but some other genetic or environmental factors contribute to clinical heterogeneity. The Bsu361 retriction site analysis was performed in 7 families and provided clear results for the diagnosis of heterozygotes as well as homozygotes of this specific clinical form of GM1 gangliosidosis. The technique is applicable to prenatal diagnosis and genetic counseling.
Cytokine expression in the brain during the acquired immunodeficiency syndrome
Authors: Tyor William R. , Glass Jonathan D. , Griffin John W. , Becker P. Scott , McArthur Justin C. , Bezman Lena , Griffin Diane E. 
Published: January 2005

AbstractThe pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin‐1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV‐seropositive and ‐seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin‐1 and ‐6, tumor necrosis factor‐α and ‐β, and interferon γ. Levels of soluble CD4, CD8, and interleukin‐2 receptor, as well as interferon γ, tumor necrosis factor‐α, β2‐microglobulin, neopterin, and interleukin‐6 and ‐1 β were assayed in the cerbrospinal fluid and plasma of many of these individuals during life. The HIV‐seropositive group included individuals without neurological disease, those with CNS oppotunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present, on microglial cells, which were frequently positive for tumor necrosis factor‐α. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin‐1 and interferon γ and less frequently for tumor necrosis factor and interleukin‐6. There were gliosis and significant increases in MHC class II antigen, interleukin‐1, and tumor necrosis factor‐α in HIV‐positive patients compared to HIV‐negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, β2‐microglobulin, and neopterin. There was no correlationin HIV‐positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of “immune activation” in the brains of HIV‐positive compared to HIV‐negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy.