bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuropathology of preclinical and clinical lateonset Alzheimer's disease
Authors: Troncoso Juan C. , Cataldo Anne M. , Nixon Rallph A. , Barnett Jody L. , Lee Michael K. , Checler Frederic , Fowler David R. , Smialek John E. , Crain Barbara , Martin Lee J. , Kawas Claudia H. 
Published: January 2005

AbstractWe report on the neuropathological examinations of a 74‐year‐old woman with Alzheimer's disease (AD) and of her 47‐year‐old nondementd daughter. The brain of the mother showed fully developed pathological changes of AD. By contrast, the brain of the daughter revealed only perineuronal deposition of diffuse amyloid in cerebral cortex and striking abnormalities of the endosomallysosomal system, without neurofibrillary, glial, or microglial changes. These observations suggest that amyloid deposition and endosomal‐lysosomal changes are early events in late‐onset AD and that they may precede the onset of dementia of several decades.
Amyloid myopathy: An underdiagnosed entity
Authors: Spuler Simone , Emslie‐Smith Alison , Engel Andrew G. 
Published: January 2005

AbstractAmyloidosis can involve multiple organs, including kidney, heart, peripheral nerve, skin, joints, and skeletal muscle, but rarely presents as a myopathy. We studied 13 adults with muscle weakness for between 3 months and 4 years in whom the diagnosis of systemic amyloidosis was unsuspected before or until just before the time of the muscle biopsy. All muscle specimens demonstrated congophilic deposits around blood vessels and muscle fibers, some necrotic and regenerating fibers, and signs of mild denervation. Immunostains in 10 patients revealed immunoglobulin amyloidosis in 7 and gelsolin amyloidosis in 1. Apolipoprotein E colocalized with the congophilic deposits in all 10, and a C‐terminal epitope of the β‐amyloid precursor protein was detected in 6. The frequency of the diagnosis of amyloid myopathy increased 10‐fold when we adopted the fluorescent Congo red stain as a routine procedure in assessing muscle biopsy specimens.
Temporal ictal electroencephalographic frequency correlates with hippocampal atrophy and sclerosis
Authors: Vossler David G. , Kraemer Dinna L. Abson , Knowlton Robert C. , Kjos Bent O. , Rostad Steve W. , Wyler Allen R. , Haltiner Alan M. , Hasegawa Hisanori , Wilkus Robert J. 
Published: January 2005

AbstractWe studied 328 complex partial seizures (CPS) in 63 consecutive patients with temporal lobe epilepsy who underwent scalp electroencephalography/video monitoring, magnetic resonance imaging (MRI), and surgery. The initial ictal discharge (IID), defined as the first sustained electrical seizure pattern localized to the surgical site, was determined. If the IID was rhythmic waves, the median frequency was measured. To determine if IID frequency correlates with hippocampal atrophy (HA) or sclerosis (HS), hippocampal volume ratios (HVRs) were measured (n = 52) or assessed visually (n = 11) on MRI, and mesial temporal histopathology specimens (n = 22) were graded for HS. Sixteen patients (25%) had no or mild HA (HVR = 0.78‐1.02), and 47 patients (75%) had moderate‐to‐marked unilateral (HVR = 0.33−0.76), or bilateral, HA. Theta frequency IIDs were significantly more commonly associated with moderate‐to‐marked HA than were delta IIDs. Theta frequency IIDs occurred in 19% of patients with mild or no HA, and 79% of patients with moderate‐to‐marked HA; delta IIDs occurred in 63% of patients with little to no HA, and 13% of those with moderate‐to‐marked HA. In addition, the median IId frequency inversely correlated with HVR and directly correlated with HS severity. In conclusion, faster frequency rhythmic IIDs during temporal lobe CPS correlate with greater degrees of ipsilateral HA on MRI, and higher grades of HS.
Neuroanatomical and neurocognitive differences in a pair of monozygous twins discordant for strictly defined autism
Authors: Kates Wendy R. , Mostofsky Stewart H. , Zimmerman Andrew W. , Mazzocco Michele M. M. , Landa Rebecca , Warsofsky Ilana S. , Kaufmann Walter E. , Reiss Allan L. 
Published: January 2005

AbstractIn this study, we investigated the neuroanatomical similarities and differences between a pair of monozygotic, 7.5‐year‐old twin boys discordant for strictly defined autism, to identify neuroanatomical pathways that are impaired in individuals with autism. Although the unaffected twin did not fulfill the traditional diagnostic criteria for autism, he displayed constrictions in social interaction and play that were consistent with the broader phenotype for autism that has been described in nonautistic co‐twins. Magnetic resonance imaging scans were obtained for each brother and compared with the scans of 5 age‐ and sex‐matched unaffected peers. Quantitative analysis of brain anatomy revealed that the affected twin had markedly smaller caudate, amygdaloid, and hippocampal volumes, and smaller cerebellar vermis lobules VI and VII, in comparison with his brother. Both twins evidenced disproportionately reduced volumes of the superior temporal gyrus and the frontal lobe relative to the comparison sample. The results suggest the dysfunction of two separate but overlapping neuroanatomical pathways, ie, one subcortical network differentiating the twins from each other that may underlie the traditional neurobehavioral phenotype for strictly defined autism, and a second cortical network differentiating the twins from the comparison sample that may lead to the broader phenotype for autism.
Longitudinal study of cerebrospinal fluid levels of tau, Aβ1–40, and Aβ1–42(43) in Alzheimer's disease: A study in Japan
Authors: Kanai M. , Matsubara E. , Isoe K. , Urakami K. , Nakashima K. , Arai H. , Sasaki H. , Abe K. , Iwatsubo T. , Kosaka T. , Watanabe M. , Tomidokoro Y. , Shizuka M. , Mizushima K. , Nakamura T. , Igeta Y. , Ikeda Y. , Amari M. , Kawarabayashi T. , Ishiguro K. , Harigaya Y. , Wakabayashi K. , Okamoto K. , Hirai S. , Shoji M. 
Published: January 2005

AbstractTo clarify the alterations of tau, amyloid β protein (Aβ) 1–40 and Aβ1–42(43) in the cerebrospinal fluid (CSF) that accompany normal aging and the progression of Alzheimer's disease (AD), CSF samples of 93 AD patients, 32 longitudinal subjects among these 93 AD patients, 33 patients with non‐AD dementia, 56 with other neurological diseases, and 54 normal control subjects from three independent institutes were analyzed by sensitive enzyme‐linked immunosorbent assays. Although the tau levels increased with aging, a significant elevation of tau and a correlation between the tau levels and the clinical progression were observed in the AD patients. A significant decrease of the Aβ1–42(43) levels and a significant increase of the ratio of Aβ1–40 to Aβ1–42(43) were observed in the AD patients. The longitudinal AD study showed continuous low Aβ1–42(43) levels and an increase of the ratio of Aβ1–40 to Aβ1–42(43) before the onset of AD. These findings suggest that CSF tau may increase with the clinical progression of dementia and that the alteration of the CSF level of Aβ1–42(43) and the ratio of Aβ1–40 to Aβ1–42(43) may start at early stages in AD. The assays of CSF tau, Aβ1–40, and Aβ1–42(43) provided efficient diagnostic sensitivity (71%) and specificity (83%) by using the production of tau levels and the ratio of Aβ1–40 to Aβ1–42(43), and an improvement in sensitivity (to 91%) was obtained in the longitudinal evaluation.
Small‐fiber sensory neuropathies: Clinical course and neuropathology of idiopathic cases
Authors: Holland Neil R. , Crawford Thomas O. , Hauer Peter , Cornblath David R. , Griffin John W. , McArthur Justin C. 
Published: January 2005

AbstractWe describe the clinical features, natural history, and neuropathology of 32 patients presenting with “burning feet”, for whom no specific cause was identified. All had neuropathic pain in the feet and morphological abnormalities of cutaneous innervation in skin obtained using punch biopsy. Most (29) had an abnormal sensory examination. All had normal strength, proprioception, tendon reflexes, and nerve conductions. Two clinical patterns were apparent, based on natural history and spatial distribution of cutaneous denervation. Most (28) patients presented with neuropathic pain initially restricted to the feet and toes but extending more proximally to involve the legs and hands with time. Intraepidermal nerve fiber (IENF) density was most severely reduced distally, with more normal IENF densities in skin from proximal sites. In contrast, a minority (4) presented with the abrupt onset of generalized cutaneous burning pain and hyperesthesia. In these patients, IENF densities were reduced in skin from both proximal and distal sites. Absolute IENF densities in calf skin were reduced below the lower limit of normal (5th percentile) in 26 (81%). Of the 6 who underwent sural nerve biopsy, 4 had selective loss of small myelinated and/or unmyelinated axons and 2 had normal histology and fiber densities despite reduced IENF densities in skin biopsy specimens. Punch skin biopsy from proximal and distal sites is a useful means of assessing these distinctive patients and may provide further insight into pathophysiology.
Frontotemporal dementia: Neuropil spheroids and presynaptic terminal degeneration
Authors: Zhou L. , Miller B. L. , McDaniel C. H. , Kelly L. , Kim O. J. , Miller C. A. 
Published: January 2005

AbstractWe compared the neuropathological changes of 6 patients with clinically diagnosed lobar dementia. In the 4 patients with histopathology consistent with frontotemporal dementia (FTD), moderate neuronal loss contrasted with marked cortical and subcortical gliosis. We found silver‐positive, carbohydrate‐rich, spheroidal enlargements of presynaptic terminals within the neuropil of specific central nervous system regions. The spheroids were immunopositive for the cytoskeletal proteins tau, the high molecular weight neurofilament subunit (NF‐H), and β‐tubulin. No abnormal tau phosphorylation and only rare ubiquitin immunoreactivity were detected in these structures. Carbohydrate modifications, including advanced glycation end products within the spheroid matrix, were confirmed by lectin binding, and by anti‐pentosidine immunoreactivity, and indicator of oxidative stress. Ultrastructurally, the spheroids consisted of unmyelinated, membrance‐enclosed structures filled with randomly arrayed pairs of filaments, approximately 8 to 10 nm in diameter, that were sparsely labeled with antibodies to unmodified tau (T14) and NF‐H. Despite clinical overlap, the central nervous systems of our FTD patients are distinguishable from those of other patients with other lobar dementias, including Pick's disease and corticobasal degeneration, by the absence of abnormally phosphorylated neuronal or glial tau inclusions. The neuropil spheroids are dystrophic changes of certain selectively vulnerable presynaptic terminals, suggesting a retrograde degenerative process in FTD.
Dopamine D2‐type agonists protect mesencephalic neurons from glutamate neurotoxicity: Mechanisms of neuroprotective treatment against oxidative stress
Authors: Sawada Hideyuki , Ibi Masakazu , Kihara Takeshi , Urushitani Makoto , Akaike Akinori , Kimura Jun , Shimohama Shun 
Published: January 2005

AbstractOxidative stress, a process in which neurotoxic oxygen free radicals cause dopaminergic neuronal degeneration, has been implicated in the degenerative process in Parkinson's disease. Glutamate‐induced neurotoxicity is a model of oxidative stress. We demonstrated that preincubation with D2‐type dopamine agonists bromocriptine and quinpirole provides neuroprotection against glutamate‐induced neurotoxicity in cultured rat mesencephalic neurons. Simultaneous administration of D2 agonists, however, did not provide neuroprotection. The protective effects were dependent on the duration of preincubation and were blocked by a D2 antagonist and a protein synthesis inhibitor. Furthermore, preincubation with D2 agonists provided neuroprotection against toxicity induced by calcium overload and exposure to superoxide anions. Confocal microscopic analysis, using 2,7‐dichlorofluorescin diacetate, revealed that bromocriptine preincubation suppressed the action of radicals on neurons. These findings indicate that dopamine D2 agonists provide protection mediated not only by the inhibition of dopamine turnover but also via D2‐type dopamine receptor stimulation and the subsequent synthesis of proteins that scavenge free radicals.
Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease
Authors: Gu M. , Cooper J. M. , Taanman J. W. , Schapira A. H. V. 
Published: January 2005

AbstractSeveral groups have identified mitochondrial complex I deficiency in Parkinson's disease (PD) substantia nigra and in platelets. A search for any mitochondrial DNA (mtDNA) mutation underlying this defect has not yet produced any consistent result. We have made use of a mtDNA‐less (μo) cell line to determine if the complex I deficiency follows the genomic transplantation of platelet mtDNA. From a preselected group of PD patients with low platelet complex I activity, 7 patients were used for detailed study. All 7 patients were used for mixed cybrid analysis and demonstrated a selective 25% deficiency of complex I activity. Individual clonal analysis of A549 μO/PD platelet fusion cybrids from 1 of the patients expressed combined complex I and IV deficiencies with 25% and 20% decreased activities in the PD clones, respectively. Histocytochemical, immunocytochemical, and cellular functional imaging studies of these clones showed the cells within the clones were heterogeneous with respect to cytochrome c oxidase (COX) function, COX I content, and mitochondrial respiratory chain activity. These results are in agreement with a previous study and support the proposition that an mtDNA abnormality may underlie the mitochondrial defect in at least a proportion of PD patients. This μo technology may serve as a means to identify the subgroup of PD patients in whom an mtDNA defect may contribute to development of the disease.
Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy
Authors: Li Mei , Miwa Shigeru , Kobayashi Yasushi , Merry Diane E. , Yamamoto Masahiko , Tanaka Fumiaki , Doyu Manabu , Hashizum Yoshio , Fischbeck Kenneth H. , Sobue Gen 
Published: January 2005

AbstractSpinal and bulbar muscular atrophy (SBMA) is an X‐linked motor neuronopathy caused by the expansion of an unstable CAG repeat in the coding region of the androgen receptor (AR) gene. To study AR protein expression in normal and SBMA individuals, we used several antibodies that recognize AR protein, and analyzed neural and nonneural tissues by immunohistochemistry and western blotting. Both the normal and the mutant AR proteins were widely distributed, predominantly, but not exclusively, in the cytoplasm of neurons regardless of the pathological involvement, and predominantly in the nuclei of the nonneural tissues in both normal and SBMA individuals, with different expression levels of AR protein among different tissues. In the motor neurons of SBMA patients, there were AR‐immunoreactive ubiquitinated nuclear inclusions that were detected by antibodies that recognize a small portion of the N terminus of the AR protein. Absence of other immunoreactive AR epitopes within the inclusion may be due to altered AR configuration, or masking of AR epitopes by other proteins, or proteolytic cleavage of the AR. Our data show that, in addition to the normal cellular distribution of the AR protein, mutant AR‐bearing nuclear inclusions are present in SBMA.
Increased long‐term potentiation in the surround of experimentally induced focal cortical infarction
Authors: Hagemann Georg , Redecker Christoph , Neumann‐Haefelin Tobias , Freund Hans‐Joachim , Witte Otto W. 
Published: January 2005

AbstractFunctional recovery after stroke is partly due to cortical reorganization on a structural as well as a functional level. Recent investigations have shown that the excitability of brain areas surrounding cortical ischemic lesions is increased, probably due to a down‐regulation of γ‐aminobutyric acid–receptor activity. There is some evidence that these changes might increase the susceptibility of the lesioned brain for adaptive changes and recovery. Here, we investigated the propensity for the induction of long‐term potentiation (LTP) in the surround of experimentally induced focal cortical infarcts in rat somatosensory cortex in vitro. By using standard paradigms, LTP induction was found to be facilitated ipsilaterally in slices of lesioned animals 1 week after lesion induction. In homotopic contralateral areas, LTP was not different from control values. As LTP is commonly associated with plasticity and learning, the results provide further evidence for the lesion‐induced amplification of network plasticity, as it is required for the reshaping of cortical circuits by timely training procedures.
Ultrastructural connective tissue abnormalities in patients with spontaneous cervicocerebral artery dissections
Authors: Brandt Tobias , Hausser Ingrid , Orberk Erdem , Grau Armin , Hartschuh Wolfgang , Anton‐Lamprecht Ingrun , Hacke Werner 
Published: January 2005

AbstractThe cause of spontaneous cervicocerebral artery dissection is unknown. An underlying arteriopathy due to a connective tissue disorder has often been presumed. We studied 25 patients with proven nontraumatic dissections. The ultrastructural morphology of dermal connective tissue components was assessed by transmission electron microscopy of skin biopsies. Ultrastructural abnormalities were seen in 17 (68%) patients, resembling in some cases the aberrations found in Ehlers‐Danlos syndrome type II or III. These observations indicate a correlation of cervical artery dissections with connective tissue abnormalities. A structural abnormality in the extracellular matrix potentially caused by basic molecular defects is suggested and warrants further exploration.
Decreased striatal monoaminergic terminals in severe chronic alcoholism demonstrated with (+)[11C]Dihydrotetrabenazine and positron emission tomography
Authors: Gilman Sid , Koeppe Robert A. , Adams Kenneth M. , Junck Larry , Kluin Karen J. , Johnson‐Greene Doug , Martorello Susan , Heumann Mary , Bandekar Rajesh 
Published: January 2005

AbstractWe used (+)[11C]dihydrotetrabenazine, a new ligand for the type 2 vesicular monoamine transporter, with positron emission tomography to study striatal monoaminergic presynaptic terminals in 7 male severe chronic alcoholic subjects without Wernicke–Korsakoff disease compared with 7 male normal controls of similar ages. We found reduced specific binding in the caudate nucleus and putamen in the alcoholic group, and the difference reached significance in the putamen. Specific binding was not decreased in the thalamus, which was examined as a reference structure. We also detected deficits in blood‐to‐brain transfer rate, K1, in the same regions of the alcoholic group, with a significant difference in the putamen. K1 was unchanged in the thalamus. The finding of reduced striatal VMAT2 in severe chronic alcoholic patients suggests that nigrostriatal monoaminergic terminals are reduced, with or without loss of neurons from the substantia nigra. The findings suggest that the damaging effects of severe chronic alcoholism on the central nervous system are more extensive than previously considered.
Silent intracerebral microhemorrhages in patients with ischemic stroke
Authors: Kwa Vincent I. H. , Franke Cees L. , Verbeeten Ben , Stam Jan ,   For the Amsterdam Vascular Medicine Group
Published: January 2005

AbstractWe compared the frequencies of signs of old intracerebral hemorrhages on brain magnetic resonance imaging scans in 66 patients with ischemic stroke, 69 with myocardial infarction, and 86 with peripheral arterial disease (a total of 221 patients). Magnetic resonance imaging scans were independently assessed by two investigators without knowledge of clinical or laboratory data. In 31 patients (14%) we found local cerebral hemosiderin deposits. In 24 patients they were clinically silent. Hemosiderin deposits were significantly more frequent in patients with ischemic stroke (26%) than in patients with myocardial infarction (4%) or peripheral arterial disease (13%). Hemosiderin deposits were associated with cerebral white matter lesions (odds ratio, 5.3; 95% confidence interval, 2.5–12.4). The odds ratios were higher in patients with severe cerebral white matter lesions. Our findings support the hypothesis that cerebral vessels of patients with ischemic stroke are more prone to rupture than those of patients with other manifestations of atherosclerotic disease, which may explain the higher incidence of intracerebral hemorrhages when these patients are treated with oral anticoagulants. The microhemorrhages were associated with cerebral white matter lesions, which suggests that they are another manifestation of cerebral small‐vessel disease.
Evoked potential abnormality scores are a useful measure of disease burden in relapsing–remitting multiple sclerosis
Authors: O'Connor Paul , Marchetti Paul , Lee Liesly , Perera Maureen 
Published: January 2005

AbstractFifty patients with relapsing‐remitting multiple sclerosis were examined and studied with serial evoked potential and magnetic resonance imaging (MRI) measurements as part of a clinical trial. An evoked potential abnormality score (EPAS) for each testing session was calculated consisting of the total number of abnormal tests. The EPAS correlated well with Expanded Disability Status Scale (EDSS) at years 0, 1, and 2, with Spearman correlation coefficient scores of 0.68, 0.66, and 0.72, respectively. MRI lesion volume correlations ranged from 0.27 to 0.34 for the EDSS. EPAS are a potentially useful surrogate measure of clinical disability in relapsing‐remitting multiple sclerosis.
Search for varicella zoster virus in giant cell arteritis
Authors: Nordborg Claes , Nordborg Elisabeth , Petursdottir Vigdis , LaGuardia James , Mahalingam Ravi , Wellish Mary , Gilden Donald H. 
Published: January 2005

AbstractPolymerase chain reaction and immunohistochemical analyses of formalin‐fixed temporal arteries from 10 pathologically verified cases of giant cell arteritis did not reveal varicella zoster virus antigen or DNA.
Expression of integrins in experimental autoimmune neuritis and guillain‐barré syndrome
Authors: Previtali S. C. , Archelos J. J. , Hartung H.‐P. 
Published: January 2005

AbstractIntegrins are a subclass of adhesion molecules that mediate cell–cell and cell–extracellular matrix interactions. Integrins influence transendothelial migration of lymphocytes and monocytes and are suitable targets for experimental immunotherapy. They are critically involved in the pathogenesis of autoimmune neuritis and abnormally expressed in human neuropathies. Also, the role of integrins in myelination, neurite outgrowth, and nerve regeneration suggests that they could be involved in the recovery phase of immune‐mediated neuropathies. We investigated by immunohistochemistry the expression of a number of integrin subunits during the course of experimental autoimmune neuritis (EAN). Results were compared with the human immune neuropathy Guillain‐Barré syndrome (GBS) and extended in vitro. Inflammation and demyelination in both EAN and GBS induced the down‐regulation of β4 integrin in Schwann cells (SCs), whereas loss of α2 was noted only in EAN. When axonal loss was present, SCs displayed α5integrin, in both EAN and GBS. In vitro, basal lamina and inflammatory cytokines modulated the expression of β4 in SCs, but they did not influence α2 and α5 expression. Finally, integrins were differentially expressed in blood vessels during EAN. In conclusion, the spatiotemporal changes in integrin expression may be used to characterize, stage, and better understand the pathogenesis and evolution of inflammation during GBS and EAN. This may help to establish useful, novel therapy for immune‐mediated neuropathies.