bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and virological analyses of 21 infants with exanthem subitum (roseola infantum) and central nervous system complications
Authors: Suga Sadao , Yoshikawa Tetsushi , Asano Yoshizo , Kozawa Toru , Nakashima Toshihiko , Kobayashi Ikuko , Yazaki Takehiko , Yamamoto Hiroko , Kajita Yaji , Ozaki Takao , Nishimura Yataka , Yamanaka Tarsuhiro , Yamada Akira , Imanishi Jiro 
Published: January 2005

AbstractTwenty‐one infants who had virologically confirmed exanthem subitum and central nervous system (CNS) complications were studied to elucidate the clinical fearures, laboratory and virological findings, and outcome. The primary infection with human herpesvirus 6 was confirmed by isolation of the virus from blood, a significant rise in the antibody titeres to the virus, or both. All convulsive seizures (15 generalized and 6 focal) occurred during the pre‐eruptive stage of exanthem subitum. Four infants with encephalities/encephalopathy had more severe clinical features with abnormalities demonstrated on electroencephalograms and cerebral computed tomograms. All infants except those with encephalities/encephalopathy recovered without any sequelae. One infant with encephalities/encephalopathy developed epilepsy and another one died. Human herpesvirus 6 DNA amplified by the nested polymerase chain reaction method was detected in the cerebrospinal fluid of 6 infants, including 3 with encephalities/encephalopathy, of 11 parients examined by the fifthy day of the illness. These findings suggest thar CNS complications including encephalitis/encephalopathy occur at the pre‐eruptive stae of exanthem subitum, that human herpesvirus 6 invades the CNS in some patients, and that the outcome is not always benign.
Reduction of low‐molecular‐ weight acid phosphatase activity in Alzheimer brains
Authors: Shimohama Shun , Fujimoto Sadaki , Taniguchi Takashi , Kameyama Masakuni , Kimura Jun 
Published: January 2005

AbstractRecent studies in Alzheimer brains have shown aberrant protein phosphorylation, suggesting an afteration in protein kinases and/or phosphoprotein phosphatases. In the present stydy, the activity of acid phospharase was investigated in samples repared from postmortem normal human and alzheimer barains. p‐Nitrophenyl phosphate, a nonprotein phosphoester, was used as a substrate for acid phosphatase. The separation profile on Sephadx G0‐100 gel filtration chromatography revealed that two major forms of high‐molecular‐weight and low‐molecular‐weight acid phosphatse were present in the crude extracts of both rat and human brains. Another class of zinc ion (Zn2+)– dependent acid p‐nitrophenyl phosphatase was also detected in rat and human brains. In Alzheimer brains, the low‐molecular‐weight acid phosphatase activity was significantly decreased compared to that in control brains; however, the high‐molecular weight and Zn2+ dependent acid phosphatase activity in control and alzheimer brains was not differnt. These results suggest that reduced activity of the low‐molecular‐weight acid phosphatase, which prossesses phosphotyrosine protein phosphatase activity, might be linkd to aberrant protein tyrosine phosphorylation found in Alzheimer brains.
Mitochondrial encephalomyopathy, lactic acidosis, stroke‐like episodes (MELAS): Clinical, radiological, pathological, and genetic observations
Authors: Koo Betty , Becker Laurence E. , Chuang Sylvester , Merante Frank , Robinson Brian H. , MacGregor Daune , Tein Ingrid , Ho Vincent B. , McGreal Douglas A. , Wherrett John R. , Logan William J. 
Published: January 2005

AbstractWe reviewed 10 patients (5 males, 5 females) with mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes. The age of symptom onset ranged from 3 months to 12 years. All had lactic acidosis, multiple stroke‐like events with secondary neurological deficits, radiological changes of progressive brain infarction, and muscle biopsy showing ragged‐red fibers. In patients with earlier onset of symptoms (<2 yr), involvement tended to be more diffuse, with failure to thrive and early onset of delayed development. Patients whose symptoms appeared later tended to have focal neurological deficits with migraine‐like headache, and a rate of cognitive regression reflecting the rapidity of disease progression. Radiological changes included multiple areas of infarction with initial predilection for parietal occipital areas, progressing to generalized atrophy. Pathological findings in muscle biopsies included type 1 fiber predominance, ragged‐red fibers, increased intermyofibrillar lipid deposition, and abnormal mitochondria. Four patients showed mitochondrial DNA tRNA mutation at position 3,243. No difference was noted in clinical, radiological, or pathological findings in patients with and without this mutation, suggesting that multiple sites of point mutation may give rise to mitochondrial encephalomyopathy, lactic acidosis, and stroke‐like episodes.
Diffuse microgliosis associated with cerebral atrophy in the acquired immunodeficiency syndrome
Authors: Gelman Benjamin B. 
Published: January 2005

AbstractThe cause of cerebral atrophy in patients with acquired immunodeficiency syndrome (AIDS) is obscure because human immunodeficiency virus type 1 (HIV‐1)‐related histopathological changes hardly correlate with cerebral atrophy. In this study, brain ventricular expansion was compared to the frontal lobe density of mononuclear and astroglial cells at autopsy. Twenty‐eight male patients with AIDS displaying varying degrees of atrophy were compared to 17 age‐matched male control subjects without AIDS or atrophy. An index of ventricular expansion was measured in uniformly sliced, formalin‐fixed brain specimens, and immunochemically marked cells in coronal sections of the left superior frontal gyrus (Brodmann area 8) were quantified by field counting and planimetry. In the cortex, diffuse ferritin‐stained microglia and glial fibrillary acidic protein‐positive astrocytes were about twice as numerous in the patients with AIDS. Sixty‐five percent (18/28) of the patients with AIDS had a microglial cell density greater than 2 standard deviations above the control mean. Microglial cell density was correlated positively with the severity of ventricular expansion (r = 0.71, p <0.0001), while hypertrophied astroglial cells were very weakly related. In white matter, Ham‐56–‐positive macrophages and glial fibrillary acidic protein‐positive astrocytes were not meaningfully correlated with the index of ventricular expansion. Brain ventricular expansion and diffuse cortical microgliosis are highly prevalent anomalies in patients with AIDS, and their interrelationship may be more important than previously recognized.
When does human brain development end? Evidence of corpus callosum growth up to adulthood
Authors: Pujol Jesús , Vendrell Pere , Junqué Carme , Martí‐Vilalta Josep L. , Capdevila Antoni 
Published: January 2005

AbstractTo locate structural changes in the brain accounting for the increasing effectiveness in cognition and skills that occurs at the final stage of behavioral development, we attempted to determine the age at which the corpus callosum completes its active growth period. We assessed the growth rate of the corpus callosum by measuring its area twice on midsagittal magnetic resonance imaging scans separated by a 2‐year interval, in a series of 90 subjects with a wide range of ages. We observed an increase in the size of the corpus callosum as long as human mentation expands, up to the middle 20s. Clinical and experimental data about the corpus callosum, together with the present findings, suggest that the corpus callosum is part of the highest order‐latest maturing neural network of the brain.
Quantitative cerebrospinal fluid cytology in patients receiving intracavitary chemotherapy
Authors: Russack Valentina , Kim Sinil , Chamberlain Marc C. 
Published: January 2005

AbstractCytological evaluation of cerebrospinal fluid (CSF) is an important means of following response to intracavitary chemotherapy for leptomeningeal malignancy. We studied the feasibility of quantitative cytological evaluation by retrospective analysis of serial CSF specimens from 7 patients receiving phase I intracavitary chemotherapy for leptomeningeal malignancy who had persistent malignant cytology. Three to 34 CSF specimens per patient obtained over a 3‐ to 48‐week period were reviewed. Significant (five‐ to 10‐fold or greater) reductions in numbers of malignant cells in CSF during treatment could be identified in specimens otherwise diagnosed as positive. Quantitative CSF cytological evaluation is neither overly time consuming nor tedious to perform and may provide useful clinical information.
Visual evoked potentials in adrenolukodystrophy: A trial with glycerol trioleate and Lorenzo oil
Authors: Kaplan Peter W. , Tusa Ronald J. , Shankroff Jan , Heller Joellen , Moser Hugo W. 
Published: January 2005

AbstractAdrenoleukodystrophy is an X‐linked metabolic disorder with very‐long‐chain fatty acid (VLCFA) accumulation and multifocal nervous system demyelination, often with early involvement of visual pathways. Dietary therapy with glycerol trioleate and glycerol trieucate (Lorenzo oil) diminishes VLCFA levels. In a study of patients with the adrenomyeloneuropathy phenotype of adrenolukodystrophy, we used pattern‐reversal visual evoked potentials to evaluate visual pathways before and after treatment. Of 108 patients tested, all 26 women and 68 of the 82 men had normal potentials at baseline. Seventy patients were retested at 1 year, at which time VLCFA levels were markedly diminished. Of them, the responses in the 10 men who showed abnormalities at baseline remained abnormal; the latencies in 4 men with initially normal responses became abnormal. No patients improved. There were no correlations between disease duration prior to treatment, baseline P100 latencies, VLCFA levels, or the change in P100 latencies and VLCFA levels after dietary treatment for 1 year. Pattern‐reversal visual evoked potentials were abnormal in 17% of the men with adrenoleukodystrophy, and there was no evidence that reduction of VLCFA levels improved or retarded visual pathway demyelination.
Metachromatic leukodystrophy: Multiple nonfunctional and pseudodeficiency alleles in a pedigree: Problems with diagnosis and counseling
Authors: Francis Gordon S. , Bonni Azad , Shen Ning , Hechtman Peter , Yamut Bassem , Carpenter Stirling , Karpati George , Chang Patricia L. 
Published: January 2005

AbstractMetachromatic leukodystrophy is due to deficiennt activity of arylsulfatse A, an enzyme important in myelin catabolism. The deficiency can be caused by different point mutations in the gene coding for arylsulfatase A (nonfunctional alleles). In addition, certain mutations result in low levels of enzyme activity detectable with artificial substrates in vitro but no clinical dysfunction (pseudodeficiency alleles). The described family has various combinations of normal, nonfunctional, and pseudodeficiency alleles that presented diagnostic and counseling dilemmas which were resolved at the genomic levle. We find no evidence that compound beterozygote individuals have subclinical involvement of the nervous system. We report the clinical, pathological, electrophysiological, imaging, biochemical, and genetic data of this family and discuss the difficulties in analyzing such pedigrees.
Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer's disease
Authors: Scheff Stephen W. , Sparks D. Larry , Price Douglas A. 
Published: January 2005

AbstractWe quantified the synaptic density in the entorhinal cortex (Brodmann area 28) in autopsy material from 10 individuals with Alzheimer's disease and compared them to 11 age‐matched, postmortem‐matched control subjects without dementia, using standard electron microscopy. The statistical data showed no change in synaptic density between control and Alzheimer subjects, in either lamina III or V of the cortex. There were no correlations between synaptic density and synaptic apposition length or density of senile plaques. The entorhinal cortex stands in marked contrast to other cortical areas that show a significant decline in synaptic numbers with Alzheimer's disease. This preservation of synaptic numbers may be related to a plasticity response that is greater in the entorhinal area than in other areas of the cortex.
The transport of L‐6‐fluorodopa and its metabolites from blood to cerebrospinal fluid and brain
Authors: Hammerstad John P. , Pate Brian D. , Hewitt Kellie A. , Chan Grace L‐Y. , Ruth Thomas J. , Calne Donald B. 
Published: January 2005

AbstractThe transport of L‐6‐fluorodopa and its major metabolites from the blood to the brain, cerebrospinal fluid (CSF), and muscle was studied in carbidopa‐pretreated cynomolgus monkeys. A bolus intravenous injection of 18F‐L‐6‐fluorodopa was followed by serial positron emission tomography scans and sampling of cisternal CSF and arterial blood. The relative concentrations of L‐6‐fluorodopa and its metabolites were determined in blood plasma and CSF by highperformance liquid chromatography. Raising the blood concentration of phenylanine by intraperitoneal injection markedly reduced the accumulation of tracer in the brain. This indicates that L‐6‐fluorodopa and 3‐O‐methylfluorodopa, like native L‐dopa and its O‐methylated derivative, are transported at the brain capillary by the large neutral amino acid carrier‐mediated system, which is subject to saturation and competition by other large neutral amino acids (such as phenylalanine) at physiological plasma concentrations. In contrast, administration of phenylalanine had no effect on the accumulation of tracer either in muscle, or as L‐6‐fluorodopa and 3‐O‐methylfluorodopa, in CSF. This suggests that the transport of L‐dopa and its derivatives at the blood‐CSF barrier differs from the transport at the blood‐brain barrier and also that measurement of CSF L‐dopa is not a good index of the transport and pharmacokinetics of L‐dopa in the brain. However, the effect of phenylalanine administration in reducing the concentration of fluorohomovanillic acid in the CSF suggests that the concentration of homovanillic acid in the CSF is an accurate reflection of dopamine turnover in the brain.
Oxidative damage to mitochondrial DNA shows marked age‐dependent increases in human brain
Authors: Mecocci Patrizia , MacGarvey Usha , Kaufman Allan E. , Koontz Deborah , Shoffner John M. , Wallace Douglas C. , Beal M. Flint 
Published: January 2005

AbstractA major theory of aging is that oxidative damage may accumulate in DNA and contribute to physiological changes associated with aging. We examined age‐related accumulation of oxidative damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in human brain tissue. We measured the oxidized nucleoside, 8‐hydroxy‐2′‐deoxyguanosine (OH8dG), in DNA isolated from 3 regions of cerebral cortex and cerebellum from 10 normal humans aged 42 to 97 years. The amount of OH8dG, expressed as a ratio of the amount of deoxyguanosine (dG) or as fmol/μg of DNA, increased progressively with normal aging in both nDNA and mtDNA; however, the rate of increase with age was much greater in mtDNA. There was a significant 10‐fold increase in the amount of OH8dG in mtDNA as compared with nDNA in the entire group of samples, and a 15‐fold significant increase in patients older than 70 years. These results show for the first time that there is a progressive age‐related accumulation in oxidative damage to DNA in human brain, and that the mtDNA is preferentially affected. It is possible that such damage may contribute to age‐dependent increases in incidence of neurodegenerative diseases.
Herpes simplex type 1 encephalitis in acquired immunodeficiency syndrome
Authors: Tan Stella V. , Guiloff Roberto J. , Scaravilli Francesco , Klapper Paul E. , Cleator Graham M. , Gazzard Brian G. 
Published: January 2005

AbstractA severe acute necrotizing herpes simplex virus type 1 encephalitis, apparently mediated by macrophages or cytokines or both, was seen in a patient with acquired immunodeficiency syndrome. The necrosis had a distribution similar to that seen in immunocompetent subjects. Viral inclusions were abundant and meningeal reaction was minimal, as previously described in one anergic patient.
Cerebrospinal fluid inhibits Alzheimer β‐amyloid fibril formation in vitro
Authors: Wisniewski Thomas , Castano Eduardo , Ghiso Jorge , Frangione Blas 
Published: January 2005

AbstractAlzheimer's disease is characterized by the deposition of β‐protein (Aβ) as amyloid. Recently, it was found that Aβ is a normal component of serum and cerebrospinal fluid. Synthetic peptides homologous to Aβ form amyloid‐like fibrils spontaneously in water or physiological solutions. Using a peptide homologous to Aβ1–40, we find that fibril formation is inhibited by the presence of cerebrospinal fluid.
Neural degeneration and the transport of neurotransmitters
Authors: Edwards Robert H. 
Published: January 2005

AbstractA number of neurodegenerative diseases selectively affect distinct neuronal populations, but the mechanisms responsible for selective cell vulnerability have generally remained unclear. The toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) reproduces the selective degeneration of dopaminergic neurons in the substantia nigra characteristic of Parkinson's disease. The plasma membrane dopamine transporter mediates this selective toxicity through accumulation of the active metabolite N‐methyl‐4‐phenylpyridinium (MPP+). In contrast, the vesicular amine transporter protects against this form of injury by sequestering the toxin from its primary site of action in mitochondria. Together with the identification of defects in glutamate transport from patients with amyotrophic lateral sclerosis, these observations suggest that neurotransmitter transport may have a major role in neurodegenerative disease. The recent cloning of cDNAs encoding these transport proteins will help to explore this hypothesis.
Inhibition of acute, experimental autoimmune encephalomyelitis by the synthetic immunomodulator linomide
Authors: Karussis D. M. , Lehmann D. , Slavin S. , Vourka‐Karussis U. , Mizrachi‐Koll R. , Ovadia H. , Ben‐Nun A. , Kalland T. , Abramsky O. 
Published: January 2005

AbstractLinomide (LS‐2616, quinoline‐3‐carboxamide) is a synthetic immunomodulator that stimulates natural killer cell activity and activates several lymphocytic subpopulations in experimental animals and humans. In this study we determined the effect of oral treatment with linomide on the development of experimental autoimmune encephalomyelitis, an animal model for immune‐mediated human demyelinating disorders. Experimental autoimmune encephalomyelitis was induced in SJL/J mice and in an outbred strain of rats (Sabra) by subcutaneous injection of spinal cord homogenate in adjuvant followed by inoculation with Bordetella pertussis. Linomide was administered in drinking water, at an estimated dose of 50 to 100 mg/kg/day. None of the linomide‐treated mice (0/41) and Sabra rats (0/15) developed any clinical or pathological signs of experimental autoimmune encephalomyelitis, whereas almost all control animals (48/53 and 18/19, respectively) were severely paralyzed and 64.5% died from the disease. Lymphocytes obtained from linomide‐treated animals had reduced in vitro proliferative responses to guinea pig myelin basic protein, proteolipid protein of the myelin, and tuberculin‐purified protein derivative, unlike antigen‐independent proliferation which was rather unaffected. Natural killer cell activity (tested by a cytotoxic assay on radiolabeled YAC‐1 target cells) was significantly enhanced in mice treated with linomide. Our results indicate that modulation of the immune system with linomide leads to complete inhibition of experimental autoimmune encephalomyelitis in the absence of systemic immunosuppression. Linomide could therefore be of use in future clinical trials for the treatment of human autoimmune demyelinating disorders.
Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis
Authors: Katz David , Taubenberger Jeffery K. , Cannella Barbara , McFarlin Dale E. , Raine Cedric S. , McFarland Henry F. 
Published: January 2005

AbstractMagnetic resonance imaging is a highly sensitive method for the detection of the lesions of multiple sclerosis and renders possible the study and the evolution of early lesions. Previous reports on magnetic resonance imaging following gandolinium‐diethylenetriamine pentaacetic acid (Gd‐DTPA) injection demonstrated that new lesions can be recognized by contrast enhancement. The pathological basis of these observations is uncertain. We have had the opportunity to study at autopsy the brain of a patient with chronic progressive multiple sclerosis who suffered acute worsening leading to death. Magnetic resonance imaging performed 10 days and 4 weeks prior to death showed new Gd‐DTPA‐enhanced lesions in the posterior hemispheric white matter adjacent to the lateral ventricles. Light microscopic examination of these areas demonstrated them to be fresh lesions comprising intense inflammatory activity and dense perivascular cuffs within an edematous lesion center and a striking parenchymal mononuclear cell infiltration at the margins of the lesions. Lesions that were demonstrated by increased signal on T2‐weighted images, but were not enhanced following administration of Gd‐DTPA, were all of the chronic type, either inactive or active. None of these showed the intense inflammatory activity of the acute lesions and most displayed fibrous astrogliosis.
Evidence for a central cholinergic effect of high‐dose thiamine
Authors: Meador K. J. , Nichols M. E. , Franke P. , Durkin M. W. , Oberzan R. L. , Moore E. E. , Loring D. W. 
Published: January 2005

AbstractIn vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetycholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double‐blind, placebo‐controlled, double‐crossover design. Drug effects were assessed by P3 event‐related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages.
Molecular genetics in neurology
Authors: Martin Joseph B. 
Published: January 2005

AbstractThere has been remarkable progress in the identification of mutations in genes that cause inherited neurological disorders. Abnormalities in the genes for Huntington disease, neurofibromatosis types 1 and 2, one form of familial amyotrophic lateral sclerosis, fragile X syndrome, myotonic dystrophy, Kennedy syndrome, Menkes disease, and several forms of retinitis pigmentosa have been elucidated. Rare disorders of neuronal migration such as Kallmann syndrome, Miller‐Dieker syndrome, and Norrie disease have been shown to be due to specific gene defects. Several muscle disorders characterized by abnormal membrane excitability have been defined as mutations of the muscle sodium or chloride channels. These advances provide opportunity for accurate molecular diagnosis of at‐risk individuals and are the harbinger of new approaches to therapy of these diseases.