bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage to the Huntington's disease locus in a family with unusual clinical and pathological features
Authors: Zweig Richard M. , Koven Suzanne J. , Hedreen John C. , Maestri Nancy E. , Kazazian Haig H. , Folstein Susan E. 
Published: January 2005

AbstractWe used the anonymous DNA probe, D4S10 (G8), Known to be linked to the Huntington's disease (HD) locus, to confirm inheritance at that locus in a family in whom most affected individuals had atypical clinical and pathological features. Their clinical features were similar to the Westphal variant (usually seen in juvenile‐onset HD) but they had onset in adult life, and in contrast to juvenile‐onset HD, their course of illness was prolonged. Most family members had been repeatedly misdiagnosed during life because of the absence of chorea and prominence of long‐tract signs. In 2 patients who died, neuropathological examination at autopsy revealed prominent involvement of brainstem and spinal cord structures, and in 1, mild neostriatal atrophy relative to duration of the disease. The study demonstrates the usefulness of genetic linkage analysis as a diagnostic tool in families with atypical forms of HD. This method allows study of phenotypic variations that can be inherited at or near the HD locus and implies either multiple alleles at the locus gene, modifies of a single allele, or another locus in the same region causing a dominantly inherited neurodegenerative disease.
Molecular biology of duchenne and Becker's muscular dystrophy: Clinical applications
Authors: Gutmann David H. , Fischbeck Kenneth H. 
Published: January 2005

AbstractRecent advances in molecular genetics have led to the isolation of the gene defective in patients with Duchenne and Becker's muscular dystrophy and the characterization of its protein product, dystrophin. In this communication, the developments culminating in the identification of the Duchenne muscular dystrophy locus are reviewed. The practical applications of this research and pitfalls that limit prenatal diagnosis and carrier detection are discussed.
Cerebrospinal fluid quinolinic acid concentrations are increased in acquired immune deficiency syndrome
Authors: Hayes Melvyn P. , Rubinow David , Lane Clifford , Markey Sanford P. 
Published: January 2005

AbstractDementia and brain atrophy are established features of a large proportion of patients with acquired immune deficiency syndrome (AIDS). To investigate a potential mechanism for atrophy in AIDS, we measured the concentration of the endogenous neurotoxin quinolinic acid in the cerebrospinal fluid of 10 patients with AIDS and found that they had 3‐fold higher quinolinic acid concentrations than 9 age‐matched control subjects: 53.8 10.7 pmol/ml versus 18.4 3.4 pmol/ml, respectively (p 0.005). It remains to be determined whether increased brain quinolinic acid concentrations are involved in the pathogenesis of the neuropathology of AIDS.
Tau in situ hybridization in normal and alzheimer brain: Localization in the somatodendritic compartment
Authors: Kosik Kenneth S. , Crandall James E. , Mufson Elliott J. , Neve Rachael L. 
Published: January 2005

AbstractTau messenger RNA in situ hybridization in human postmortem brain revealed that neurons are the predominant cell type labeled. The probe used includes the nucleotide sequence coding for the amino acids recognized by the well‐characterized tau monoclonal antibodies 5E2 and tau 1. The distribution of the tau RNA is abundant throughout the neuronal somata and into the proximal parts of dendrites of pyramidal cells in the cerebral cortex and the hippocamps. The distal extent to which silver grains cold be visualized in the pyramidal cell dendrite was comparable to that seen with a probe to ribosomal RNA. In contrast to the tau probe the ribosomal probe also labeled glial cells. Sections hybridized with the tau probe and then double‐labeled with thioflavine S revealed that neurons containing neurofibrillary tangles tangles continue to synthesize tau protein.
Low‐titer antibodies reactive with HTLV‐I gag P19 in patients with chronic myeloneuropathy
Authors: Kawanishi Taketo , Akiguchi Ichiro , Fujita Masashi , Kameyama Masakuni , Hatanaka Masakazu 
Published: January 2005

AbstractTo elucidate the possible association of human T‐lymphotropic virus type I (HTLV‐I) and chronic neurological diseases, 156 serum samples from patients with various neurological diseases, including multiple sclerosis, chronic progressive myelopathy, chronic inflammatory polyradiculoneuropathy, myasthenia gravis, polymyositis, motor neuron disease, and tension headache, and healthy control subjects were examined for IgG antibodies to HTLV‐I by three independent techniques–gelatin particle agglutination test, enzyme‐linked immunosorbent assay, and Western blot assay. Specificity of antibodies was assessed by homologous competitive inhibition on Western blot assay. Six patients (3 with chronic progressive myelopathy, 1 with chronic inflammatory polyradiculoneropathy, 1 with motor neuron disease, and 1 with tension headache) had high‐titer HTLV‐I antibodies. Twelve patients (5 with multiple sclerosis, 1 with chronic progressive myelopathy, 2 with chronic inflammatory polyradiculoneuropathy, 2 with myasthenia gravis, and 2 with motor neuron disease) had low‐titer HTLV‐I antibodies that reached with a single gag protein, p19, or p24, on Western blot assay. In 4 (2 with multiple sclerosis, 1 with chronic progressive myelopathy, and 1 with chronic inflammatory polyradiculoneuropathy) of these 12, the antibodies that were all directed to p19 were determined to be specific by homologous competitive inhibition. In the remaining 8 patients (3 with multiple sclerosis, 1 with chronic inflammatory polyradiculoneuropathy, 2 with myasthenia gravis, 2 with motor neuron disease), restricted reactions against p19 or p24 were considered to be nonspecific because they were not inhibited by homologous competitive inhibition. The results suggest that in some patients chronic myeloneuropathy diagnosed as chronic progressive multiple sclerosis, chronic progressive myelopathy, and chronic inflammatory polyradiculoneuropathy may be associated with HTLV‐I or related retroviruses.
Nigrostriatal function in humans studied with positron emission tomography
Authors: Martin W. R. W. , Palmer M. R. , Patlak C. S. , Calne D. B. 
Published: January 2005

AbstractThe dopamine depletion that is characteristic of Parkinson's disease has been hypothesized to result from the combination of environmentally induced subclinical damage to the substantia nigra and the age‐related loss of additional nigral neurons. Essential to this hypothesis is the existence of deteriorating function in the nigrostriatal pathway with advancing age. The present study was undertaken with [18F]6‐fluoro‐L‐dopa and positron emission tomography to determine in vivo the effects of age on the nigrostriatal pathway in a series of 10 asymptomatic subjects (age range, 22–80 years; mean, 49.8 years). A graphical approach was used in the analysis of multiple‐time tracer‐uptake data to establish the presence of a compartment with unidirectional uptake and to calculate the rate constant, K, for uptake of [18F]6‐fluoro‐L‐dopa from blood to striatum during steady‐state, an index of the functional integrity of nigrostriatal nerve endings. There was a significant linear relationship between K and age (r = 0.80, p < 0.005) with a decrease of 53.3% over the age range studied. These results demonstrate the application of a unidirectional transfer model to the analysis of [18F]6‐fluoro‐L‐dopa and positron emission tomography data and provide in vivo confirmation of an age‐related impairment of nigrostriatal function.
Axonal regeneration on mature human brain tissue sections in culture
Authors: Crutcher Keith A. , Privitera Michael 
Published: January 2005

AbstractFresh frozen sections of the temporal lobe from patients undergoing surgical resection for the control of epilepsy were used as a substrate in tissue culture to test for neurite growth‐promoting activity. Robust neurite growth from ganglia of embryonic chicks was observed on gray matter regions of the sections and little growth was observed on white matter regions. These results indicate that the dichotomy between gray and white matter regions of the mature central nervous system in supporting neurite growth is present in human brain tissue and supports the general hypothesis that white matter in the mature central nervous system inhibits neurite regeneration but that gray matter will support neurite growth.
Idiopathic dystonia among ashkenazi jews: Evidence for autosomal dominant inheritance
Authors: Bressman Susan B. , De Leon Deborah , Brin Mitchell F. , Risch Neil , Burke Robert E. , Greene Paul E. , Shale Heidi , Fahn Stanley 
Published: January 2005

AbstractWe studied families to clarify the mode of inheritance of idiopathic torsion dystonia among the Ashkenazim. Probands had symptoms before 28 years of age, had at least one Ashkenazi grandparent, and were ascertained independently of family history and not referred by another relative. All available first‐ and second‐degree relatives were examined, and videotapes were made. Examination notes and blinded review of videotapes led to rating of dystonia as definite, probable, possible, or absent. We determined rates to illness for first‐and second‐degree relatives and calculated age‐adjusted lifetime risks. The methods of maximun likelihood and likelihood ratio goodness‐of‐fit tests were used to estimate parameters and to test dominant and recessive models of inheritance. We studied 43 probands, 146 (90.1%) of 162 living first‐degree relatives, and 96 (40.2%) of 239 living second‐degree relatives. Nineteen relatives had definite dystonia, and 2 had probable dystonia. Using definite cases only, the age‐adjusted risk for all first‐degree relatives was 15.5percnt; and for all second‐degree relatives 6.5percnt;, with no significant sex differences; parent, offspring, and sibling risks did not differ significantly. The risks were consistent with autosomal dominant inheritance with a penetrance estimated at 29.4% using definite cases only or 32.2percnt; using definite and probable cases. Assuming a disease frequency of 1/15,000, the gene frequency was estimated to be 1/9000.
Bimodal treatment with nimodipine and low‐molecular‐weight dextran for focal cerebral ischemia in the rat
Authors: Salgado Antonio V. , Jones Stephen C. , Furlan Anthony J. , Korfali Ender , Marshall Sam A. , Little John R. 
Published: January 2005

AbstractWe compared the effects of intravenous treatment with combined low‐molecular‐weight dextran and nimodipine (n = 9), or placebo (n = 10), on local cerebral blood flow after occlusion of the left middle cerebral and common carotid artery in the rat. Treatment for a total of 4 hours with low‐molecular‐weight dextran (5 mg/kg/min) and nimodipine (0.25 μg/kg/min) produced a decrease in hematocrit from 46 ± 1 to 33 ± 1% at the end of the study and a statistically significant increase in local cerebral blood flow, when compared to the control group, in 6 regions of interest: the territories of the right middle (p = 0.01), right anterior (p = 0.007), and left anterior cerebral arteries (p = 0.001) the superior (p = 0.03) and inferior border zone (p = 0.003); and white matter in the right hemisphere (p = 0.04). The ischemic volume, defined as brain volume with a cerebral blood flow of less than the critical level of 25 ml/min/100 gm was determined as a percentage of total brain volume for the control and treatment groups. The group treated with lowmolecular‐weight dextran and nimodipine showed a 31% decrease in ischemic volume (p = 0.03). These results indicate that a bimodal approach with low‐molecular‐weight dextran and nimodipine can be safely used in a model of acute stroke and has a beneficial effect on local cerebral blood flow and ischemic volume when compared with control subjects. After 4 hours, the potential exists that this treatment is therapeutic, assuming that the ischemic volume progresses to infarction.
The early risk of multiple sclerosis following isolated acute syndromes of the brainstem and spinal cord
Authors: Miller D. H. , Ormerod I. E. C. , Rudge P. , Kendall B. E. , Moseley I. F. , McDonald W. I. 
Published: January 2005

AbstractA combined clinical and magnetic resonance imaging follow‐up study was undertaken to determine the risk of early progression to multiple sclerosis in patients who present with clinically isolated lesions of the brainstem or spinal cord. Progression to multiple sclerosis was seen in 13 patients (57%) who had a brainstem syndrome and in 14 patients (42%) who had a spinal cord syndrome after mean intervals of 15 and 16 months, respectively. The risk of progression was increased by the presence of oligoclonal bands in the cerebrospinal fluid of patients with either syndrome and by the presence of disseminated brain lesions, as detected by magnetic resonance imaging, in those with a spinal cord syndrome. Follow‐up revealed evidence of multiphasic disease in 24 (69%) of 35 patients who had disseminated lesions on magnetic resonance imaging scans at presentation, suggesting that multiple sclerosis is the usual cause of such lesions.
Localization of epileptic foci with postictal single photon emission computed tomography
Authors: Rowe Christopher C. , Berkovic Samuel F. , Sia S. T. Benjamin , Austin Mark , McKay W. John , Kalnins Renate M. , Bladin Peter F. 
Published: January 2005

AbstractEffective surgical treatment of patients with intractable complex partial seizures depends on accurate preoperative seizure focus localization. We evaluated seizure localization with interictal and immediate postictal single photon emission computed tomographic images of cerebral perfusion using technetium‐99m–hexamethyl‐propyleneamineoxime (99mTc‐HMPAO) in comparison with conventional ictal electroencephalographic (EEG) localization. Thirty‐two patients with intractable complex partial seizures were studied. The mean delay from seizure onset to injection was 6.3 ± 5.3 (SD) minutes. Independent blinded observers assessed the scans for interictal hypoperfusion and postictal focal hyperperfusion. Interictal scans alone were unreliable, indicating the correct localization in 17 patients (53percnt;) and an incorrect site in 3 (9%). When interictal and postictal scans were interpreted together, the focus was correctly localized in 23 patients (72%). There was 1 false‐positive study, and 8 patients had inconclusive changes, including 2 with inconclusive depth EEG studies. Postictal hyperperfusion was predominantly mesial temporal and frequently associated with hypoperfusion of lateral temporal cortex. Secondarily generalized seizures tended to show focal hyperperfusion less often than complex partial seizures did (Fisher's exact test p = 0.09). Combined interictal and immediate postictal single photon emission computed tomography with 99mTc‐HMPAO is a useful noninvasive technique for independent confirmation of electrographic seizure localization. It may provide a suitable alternative to the use of depth electrode studies for confirmation of surface EEG findings in many patients with complex partial seizures.
Adenosine receptors in brain: Neuromodulation and role in epilepsy
Authors: Chin Jerome H. 
Published: January 2005

AbstractAdenosine is now recognized as an important endogenous modulator of neuronal excitability in the mammalian central nervous system. Adenosine is produced and released in the brain, where it exerts potent depressant effects on neuronal firing and synaptic transmission. Multiple adenosine receptor subtypes have been characterized using biochemical, electrophysiological, and radioligand binding techniques. Adenosine analogues have potent anticonvulsant actions in vitro and antagonize seizures in animals induced by a variety of mechanisms, including kindling. The future development of selective adenosine receptor agonists may provide new and more effective treatment for epilepsy.
PET Imaging of human gliomas with ligands for the peripheral benzodiazepine binding site
Authors: Junck Larry , Olson James M. M. , Ciliax Brian J. , Koeppe Robert A. , Watkins G. Leonard , Jewett Douglas M. , McKeever Paul E. , Wieland Donald M. , Kilbourn Michael R. , Starosta‐Rubinstein Simon , Mancini William R. , Kuhl David E. , Greenberg Harry S. , Young Anne B. 
Published: January 2005

AbstractHuman gliomas were imaged in vivo using ligands for the peripheral‐type benzodiazepine site (or ω3 binding site) and positron emission tomography (PET). Although gliomas have a high density of the peripheral‐type benzodiazepine binding site, PET scans with a selective ligand for this site, [11C]Ro5‐4864, failed to demonstrate higher radioactivity levels in human gliomas than in brain. In vitro studies of surgically removed specimens of human glioma demonstrated little binding of Ro5‐4864 but high levels of binding of another selective ligand, PK 11195. Scans with [11C]PK 11195 demonstrated increased radioactivity in glioma compared to brain in 8 of 10 patients. Radioactivity in tumor and the ratios of radioactivity in tumor to that in remote gray and in white matter correlated significantly with the specific activity of [11C]PK 11195, suggesting that accumulation represents saturable high‐affinity binding. We conclude that the PK 11195 manifests greater binding than Ro5‐4864 to the peripheral‐type benzodiazepine binding site on human gliomas and that human gliomas can be successfully imaged using [11C]PK 11195 and PET.
Computed tomographic patterns of proven embolic brain infarctions
Authors: Ringelstein E. Bernd , Koschorke Susanne , Holling Andreas , Thron Armin , Lambertz Heinz , Minale Carmine 
Published: January 2005

AbstractTo define patterns of infarction on computed tomography that are characteristic of embolism, as opposed to hemodynamically or microangiopathically induced brain lesions, a consecutive series of 60 patients with acute brain embolism were studied. Strokes were embolic in origin; that is, hemodynamic and in situ thrombotic stroke mechanisms had been excluded. Embolically active, cardiac disease was proved in 42 and was clinically evident in 13 patients. Five patients had suffered a stroke due to catheter‐related embolism. Computed tomography revealed pial artery territorial infarction in 55 patients (92%). In 5, the infarction had the size or location (or both) characteristic of lacunes, although shape and lack of multiplicity raised questions about this interpretation. No patient showed a low‐flow type of infarction pattern. These findings strongly support the view that (1) except for in situ thrombosis, pial artery territorial infarctions are indicative of an embolic mechanism, and (2) that the mechanism underlying lacunes is hardly, if ever, embolic.
The widespread alteration of neurites in Alzheimer's disease may be unrelated to amyloid deposition
Authors: Tabaton Massimo , Mandybur Thaddeus I. , Perry George , Onorato Michelle , Autilio‐Gambetti Lucila , Gambetti Pierluigi 
Published: January 2005

AbstractThe structural changes of Alzheimer's disease (AD) include a widespread alteration of neuronal cell processes in addition to senile plaques and neurofibrillary tangles. Since the antigenic characteristics of these abnormal neurites are similar to those of the abnormal neurites associated with the senile plaques, the question has been raised as to whether the widespread neuritic alteration is secondary to the deposition of amyloid. To answer this question, we examined brains from 2 subjects with a longer‐lasting form of subacute sclerosing panencephalitis (SSPE) characterized by the presence of numerous neurofibrillary tangles but no senile plaques, 3 subjects with AD, and 2 age‐matched controls. Light and electron immunocytochemical analyses revealed that abnormal neurites are present diffusely in SSPE cerebral cortex in the absence of amyloid deposits. These abnormal neurites were qualitatively identical to the widespread abnormal neurites of AD. The abnormal neurites, in contrast to the neurites of control brains, immunoreacted with antibodies to tau and ubiquitin. These distinctive antigenic features were due to the presence in these abnormal neurites of straight filaments, 14 to 16 nm in diameter, mixed with a few paired helical filaments. The spatial distribution of the widespread neuritic alteration correlated with that of neurofibrillary tangles in both conditions, but not with that senile plaques in AD. The present findings demonstrate that a diffuse alteration of neurites similar to that present in AD takes place independently of the deposition of amyloid in SSPE, and they are consistent with the hypothesis that in AD, also, this alteration is not secondary to the deposition of amyloid. It is suggested that the diffuse abnormality of neurites and the formation of neurofibrillary tangles in AD and SSPE, as well as in other conditions, are the expression of a widespread alteration of the neuronal cytoskeleton that involves the ubiquitin system and is likely to be caused by sustained stress conditions.
Naltrexone therapy of apnea in children with elevated cerebrospinal fluid β‐endorphin
Authors: Myer Edwin C. , Morris Dale L. , Brase David A. , Dewey William L. , Zimmerman Andrew W. 
Published: January 2005

AbstractPrevious studies have indicated increased immunoreactivity of the endogenous opioid peptide β‐endorphin in the cerebrospinal fluid (CSF) of infants under 2 years of age with apnea. To assess the role of endogeneous opioids in the pathogenesis of apnea in children, the effect of oral treatment with the opioid antagonist naltrexone was studied in apneic infants, as well as in older apneic children, with demonstrated increases in CSF immunoreactive β‐endorphin (i‐BE). In the 8 apneic infants with elevated i‐BE in lumbar CSF (range, 55–155 pg/ml normal, 17–52 pg/ml), no further apnea occurred during natltrexone therapy (1 mg/kg/day, by mouth). Five children (2–8 years old) with apnea of unknown cause had elevated CSF i‐BE (range, 74–276 pg/ml) compared to 6 age‐matched nonapneic children (range, 15–48 pg/ml). No apneic events occurred during natlrexone therapy, except in 1 child during stressful events, but apnea recurred in some patients after attempts to discontinue natlrexone treatment. Adverse effects of natlrexone included complaints of headaches in 2 children and symptoms of a narcotic withdrawal syndrome during the first 3 days of treatment in 1 child. Three children with Leigh's syndrome had elevated CSF i‐BE (range, 104–291 pg/ml) and their apnea also responded to naltrexone. We conclude that elevated endogenous opioids contribute to the pathogenesis of apnea in children and may even result in physical dependence.