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1.
J Stroke Cerebrovasc Dis ; 28(1): 229-231, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30337209

RESUMO

Medullary hemorrhage is quite rare among brain stem hemorrhage cases, thus the clinical course remains unclear. In the medulla oblongata, respiratory centers are located and previous reports indicate that medullary lesions have possible relationship with acute respiratory distress syndrome. This kind of respiratory failure is commonly caused by neurogenic pulmonary edema (NPE), which is defined as noncardiac noninfectious acute respiratory distress syndrome with changes in intracranial condition including cerebrovascular events. However, to date, very few reports have described cases with medullary hemorrhage accompanied by NPE. We experienced 2 patients with medullary hemorrhages. A 65-year-old man presented with sudden onset of headache, whose head computed tomography showed right medullary hemorrhage. Another 76-year-old woman was transferred because of sudden limb weakness and diagnosed with left medullary hemorrhage. Digital subtraction angiography showed the presence of arteriovenous fistula in the medulla oblongata and drainer veins in the second case. Both cases were complicated by acute pulmonary edema in the early phase, suggesting the possible association of the medullary hemorrhage with NPE.


Assuntos
Hemorragia Cerebral/complicações , Bulbo , Edema Pulmonar/complicações , Síndrome do Desconforto Respiratório/complicações , Idoso , Hemorragia Cerebral/diagnóstico por imagem , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Bulbo/diagnóstico por imagem , Edema Pulmonar/diagnóstico por imagem , Síndrome do Desconforto Respiratório/diagnóstico por imagem
2.
EMBO J ; 33(14): 1565-81, 2014 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-24920580

RESUMO

Fibroblasts can be directly reprogrammed into cardiomyocyte-like cells (iCMs) by overexpression of cardiac transcription factors or microRNAs. However, induction of functional cardiomyocytes is inefficient, and molecular mechanisms of direct reprogramming remain undefined. Here, we demonstrate that addition of miR-133a (miR-133) to Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Mesp1 and Myocd improved cardiac reprogramming from mouse or human fibroblasts by directly repressing Snai1, a master regulator of epithelial-to-mesenchymal transition. MiR-133 overexpression with GMT generated sevenfold more beating iCMs from mouse embryonic fibroblasts and shortened the duration to induce beating cells from 30 to 10 days, compared to GMT alone. Snai1 knockdown suppressed fibroblast genes, upregulated cardiac gene expression, and induced more contracting iCMs with GMT transduction, recapitulating the effects of miR-133 overexpression. In contrast, overexpression of Snai1 in GMT/miR-133-transduced cells maintained fibroblast signatures and inhibited generation of beating iCMs. MiR-133-mediated Snai1 repression was also critical for cardiac reprogramming in adult mouse and human cardiac fibroblasts. Thus, silencing fibroblast signatures, mediated by miR-133/Snai1, is a key molecular roadblock during cardiac reprogramming.


Assuntos
Transdiferenciação Celular/fisiologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica/fisiologia , MicroRNAs/metabolismo , Miócitos Cardíacos/metabolismo , Fatores de Transcrição/genética , Análise de Variância , Animais , Western Blotting , Transdiferenciação Celular/genética , Clonagem Molecular , Fibroblastos/citologia , Citometria de Fluxo , Técnicas de Silenciamento de Genes , Proteínas de Fluorescência Verde , Humanos , Imuno-Histoquímica , Camundongos , Análise em Microsséries , Miócitos Cardíacos/citologia , Reação em Cadeia da Polimerase em Tempo Real , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo
3.
J Infect Chemother ; 18(6): 970-2, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22576751

RESUMO

For optimum activity of daptomycin (DAP) in vitro, medium supplemented with calcium ions at physiological concentration (i.e., 50 mg/l) is required for determination of DAP minimum inhibitory concentration (MIC) in the Clinical and Laboratory Standards Institute (CLSI) broth microdilution (BMD) method. However, our literature review found that Mueller-Hinton agar (MHA) brands used for the DAP Etest had different calcium ion (Ca²âº) concentrations among the reports. For 98 clinical methicillin-resistant Staphylococcus aureus isolates previously unexposed to DAP, MICs were assessed by use of the Etest with MHA plates with different media (MHA-A, MHA-B, and MHA-C) and compared with those from the CLSI reference BMD method. The instructions for the Etest recommend MHA with Ca²âº of 25-40 mg/l for DAP MIC testing; Ca²âº concentrations for each type of MHA were 20.4 mg/l in MHA-A, 45.2 mg/l in MHA-B, and 52.0 mg/l in MHA-C. When the MIC50/MIC90 of the clinical isolates were studied, the Etest MICs for MHA-A were 1-fold dilution higher than for the BMD value. In contrast, for MHA-B they were 1-fold dilution lower, and for MHA-C MIC50 was 1.5-fold dilution lower and MIC90 was 2-fold dilution lower. MICs measured in MHA with higher Ca²âº tended to be lower. Comparison of MICs between BMD and the Etest for each MHA showed they were significantly different (p < 0.0001). The correlation coefficient was 0.6258 (p < 0.0001) for MHA-A, 0.4224 (p < 0.0001) for MHA-B, and 0.2504 (p = 0.0129) for MHA-C. Our results suggest there are differences in DAP MICs between MIC testing methods and differences between Ca²âº concentrations in MHA. For more objective and accurate measurement of DAP MICs, there should be discussion about standardization of Ca²âº in MHA.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana/métodos , Técnicas Bacteriológicas/métodos , Técnicas Bacteriológicas/normas , Cálcio/análise , Meios de Cultura , Humanos , Testes de Sensibilidade Microbiana/normas
5.
Acta Neuropathol ; 113(6): 627-36, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17431643

RESUMO

Abnormal accumulation of Abeta and tau in senile plaques (SP) and neurofibrillary tangles (NFTs) is a key event in Alzheimer's disease (AD). Here, we show that T668-phosphorylated cytoplasmic domain of APP (pT668-ACD) accumulates Abeta and tau in AD and its transgenic models. Anti-pT668 immunostaining of AD brain sections with hydrated autoclave enhancement identified SP neurites and NFTs in which pT668-ACD colocalizes with tau. We produced and examined transgenic (Tg) mice that overexpress human APP695, harboring the double Swedish/London mutation, and develop age-dependently Abeta plaques in the brain. All Abeta plaques contain co-accumulations of pT668-ACD, but co-accumulation of tau appears in only a fraction of Abeta plaques in older animals. We also examined the established tau Tg mice that overexpress the smallest human brain tau isoform and develop neuronal accumulations of tau in older animals. Examination of the old tau Tg mice showed that neuronal cells affected by tau accumulation induce co-accumulation of pT668-ACD. We speculate that in AD brains, extracellular Abeta deposition is accompanied by intracellular accumulation of pT668-ACD, followed by tau accumulation in the SP with dystrophic neurites and that neuronal cells affected by tau accumulation induce co-accumulation of pT668-ACD in NFTs. Thus, pT668-ACD is likely to mediate pathological interaction between Abeta and tau.


Assuntos
Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Citoplasma/metabolismo , Treonina/genética , Proteínas tau/metabolismo , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/genética , Precursor de Proteína beta-Amiloide/genética , Animais , Western Blotting , Citoplasma/genética , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Emaranhados Neurofibrilares/genética , Emaranhados Neurofibrilares/patologia , Fosforilação , Placa Amiloide/genética , Placa Amiloide/patologia , Proteínas tau/genética
7.
Acta Neuropathol ; 110(6): 547-56, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16228182

RESUMO

Lithium, a widely used drug for treating affective disorders, is known to inhibit glycogen synthase kinase-3 (GSK-3), which is one of the major tau kinases. Thus, lithium could have therapeutic benefit in neurodegenerative tauopathies by reducing tau hyperphosphorylation. We tested this hypothesis and showed that long-term administration of lithium at relatively low therapeutic concentrations to transgenic mice that recapitulate Alzheimer's disease (AD)-like tau pathologies reduces tau lesions, primarily by promoting their ubiquitination rather than by inhibiting tau phosphorylation. These findings suggest novel mechanisms whereby lithium treatment could ameliorate tauopathies including AD. Because lithium also has been shown to reduce the burden of amyloid-beta pathologies, it is plausible that lithium could reduce the formation of both amyloid plaques and tau tangles, the two pathological hallmarks of AD, and thereby ameliorate the behavioral deficits in AD.


Assuntos
Encéfalo/efeitos dos fármacos , Lítio/uso terapêutico , Tauopatias/tratamento farmacológico , Ubiquitina/efeitos dos fármacos , Proteínas tau/efeitos dos fármacos , Animais , Western Blotting , Encéfalo/patologia , Modelos Animais de Doenças , Eletroforese em Gel de Poliacrilamida , Quinase 3 da Glicogênio Sintase/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/metabolismo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Fosforilação , Fatores de Tempo , Proteínas tau/química
8.
J Geriatr Psychiatry Neurol ; 18(3): 142-8, 2005 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-16100103

RESUMO

Delusion of theft and phantom intruder delusion are among the most frequent delusions in dementia. The purpose of this study was to clarify the clinical characteristics of patients with these symptoms. The authors conducted a questionnaire survey; items included age, gender, dementia diagnosis, cognitive function, and activities of daily living. Other clinical characteristics were evaluated using the quality of life questionnaire for dementia. A total of 217 patients with dementia were rated. Frequencies of delusion of theft were as follows: frequent, 7%; sometimes, 11%; rare, 16%; and none, 66%. Frequencies of phantom intruder delusion were as follows: frequent, 4%; sometimes, 10%; rare, 9%; and none, 77%. Comparison between positive and negative groups with these symptoms revealed that positive groups had higher scores in 2 of 6 domains of the quality of life questionnaire for dementia, namely, negative affect and actions, and restlessness. The positive group with delusion of theft had higher scores in cognitive function and activities of daily living than did the negative group. These results suggest that negative affect and action and restlessness might be related to delusion of theft or phantom intruder delusion and that delusion of theft frequently occurs in the early stage of dementia.


Assuntos
Delusões/epidemiologia , Demência/epidemiologia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Demência/diagnóstico , Feminino , Alucinações/epidemiologia , Humanos , Japão/epidemiologia , Masculino , Inquéritos e Questionários
9.
Acta Neuropathol ; 108(6): 538-45, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15365727

RESUMO

We report here a case of orthochromatic leukodystrophy with spheroids. A 40-year-old woman developed forgetfulness. About 1 year after the onset, clinical examination confirmed global intellectual deterioration with amnesia, spatiotemporal disorientation, and impairment of judgment. At age 43, she experienced tonic-clonic convulsions several times, and died of pneumonia at the age of 44. Alzheimer's disease was suspected clinically. Pathologically, there was severe diffuse demyelination of the deep white matter of the frontal, parietal and occipital lobes with relative preservation of the subcortical U fibers. In the central demyelinated areas, myelin loss was severe with diffuse gliosis, moderate loss of axons, and many axonal spheroids. At the periphery of the severely degenerated regions, there were a lot of macrophages and most had non-metachromatic lipid granules. The cerebral cortex was intact. The neuropathological findings of this case are consistent with hereditary diffuse leukoencephalopathy with spheroids (HDLS). Ten cases of HDLS were reviewed and presented many findings in common. The gray matter was intact and U fibers were well preserved in most cases. In white matter lesions, severe loss of myelin, moderate to severe axonal loss, much axonal swelling, and the presence of macrophages and hypertrophic astrocytes were common findings. In some cases with HDLS, dementia appeared without obvious neurological manifestations in the early stage. We should remember that some cases with HDLS show clinical symptoms similar to Alzheimer's disease, especially in the early stage.


Assuntos
Doença de Alzheimer/patologia , Axônios/patologia , Encéfalo/patologia , Doenças Desmielinizantes/patologia , Adulto , Axônios/ultraestrutura , Encéfalo/ultraestrutura , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Microscopia Eletrônica de Transmissão , Tomografia Computadorizada por Raios X
10.
Artigo em Inglês | MEDLINE | ID: mdl-15276698

RESUMO

Several types of evidence suggesting that the inflammatory response system is associated with pathophysiology of schizophrenia have been accumulated. Recently, a prospective double-blind study demonstrated that supplementary treatment with celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, produced significantly greater improvement in scores on the Positive and Negative Syndrome Scale (PANSS) and on all subscales during the acute phase in patients with schizophrenia compared with risperidone alone therapy. The therapeutic effect of celecoxib on the psychopathology of schizophrenia is speculated to be based on COX activity inhibition; however, the detailed pharmacological mechanisms are unclear. To clarify whether or not COX-2 expression is altered in schizophrenia, we examined neuronal COX-2 expression in the hippocampus from cases of schizophrenia (n = 17), normal controls (n = 22), and cases of Alzheimer's disease (AD) as a positive control (n = 17). Quantitative immunohistochemical analysis demonstrated that neuronal COX-2 expression was significantly up-regulated in each CA1-4 region in Alzheimer's disease compared with controls, and that the mean COX-2 immunointensity in CA1-4 was significantly correlated with Abeta load in cases of Alzheimer's disease. In contrast, COX-2 expression was not up-regulated in any subdivision of the hippocampus in the schizophrenia group. These results suggest that celecoxib may affect the pathophysiology of schizophrenia through COX-2-independent actions rather than by inhibiting activity of up-regulated COX-2 protein.


Assuntos
Inibidores de Ciclo-Oxigenase/farmacologia , Regulação Enzimológica da Expressão Gênica/fisiologia , Hipocampo/enzimologia , Isoenzimas/biossíntese , Neurônios/enzimologia , Prostaglandina-Endoperóxido Sintases/biossíntese , Esquizofrenia/enzimologia , Sulfonamidas/farmacologia , Idoso , Doença de Alzheimer/enzimologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/biossíntese , Autopsia , Celecoxib , Ciclo-Oxigenase 2 , Inibidores de Ciclo-Oxigenase 2 , Feminino , Hipocampo/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Masculino , Proteínas de Membrana , Escalas de Graduação Psiquiátrica , Pirazóis , Esquizofrenia/tratamento farmacológico , Regulação para Cima
11.
Free Radic Biol Med ; 37(2): 176-86, 2004 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-15203189

RESUMO

We have reported that transgenic (Tg) mice overexpressing human tau protein develop filamentous tau aggregates in the CNS. We overexpressed the smallest human tau isoform (T44) in the mouse CNS to model tauopathies. These tau Tg mice acquire age-dependent CNS pathologies, including insoluble, hyperphosphorylated tau and argyrophilic intraneuronal inclusions formed by tau-immunoreactive filaments. Therefore, these Tg mice are a model that can be exploited for drug discovery in studies that target amelioration of tau-induced neurodegeneration as well as for elucidating mechanisms of tau pathology in various neurodegenerative tauopathies. Oxidative stress has been implicated in the pathogenesis of various neurodegenerative diseases, including tauopathies, and many epidemiological, clinical, and basic studies have suggested the neuroprotective effects of vitamin E in neurodegenerative diseases. To elucidate the role of oxidative damage in the pathological mechanisms of these Tg mice, we fed them alpha-tocopherol, the major component of antioxidant vitamin E. Supplementation of alpha-tocopherol suppressed and/or delayed the development of tau pathology, which correlated with improvement in the health and attenuation of motor weakness in the Tg mice. These results suggest that oxidative damage is involved in the pathological mechanisms of the tau Tg mice and that treatment with antioxidative agents like alpha-tocopherol may prevent neurodegenerative tauopathies.


Assuntos
Tauopatias/tratamento farmacológico , Tauopatias/patologia , alfa-Tocoferol/farmacologia , Animais , Antioxidantes/farmacologia , Western Blotting , Encéfalo/patologia , Sistema Nervoso Central/patologia , Modelos Animais de Doenças , Feminino , Heterozigoto , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Confocal , Microscopia de Fluorescência , Doenças Neurodegenerativas/patologia , Estresse Oxidativo , Oxigênio/metabolismo , Fosforilação , Regiões Promotoras Genéticas , Isoformas de Proteínas , Medula Espinal/patologia , Fatores de Tempo , Transgenes , Proteínas tau/química , Proteínas tau/genética
12.
Acta Neuropathol ; 107(5): 399-405, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-14991384

RESUMO

The pathophysiological basis of cognitive dysfunction, including frontotemporal dementia (FTD), in patients with amyotrophic lateral sclerosis (ALS) and ALS with dementia (ALSD) remains unclear. On the other hand, increased expression of cyclooxygenase-2 (COX-2) in the spinal cord is thought to play a pivotal role in motor neuron degeneration in ALS. In this study, to assess the relationship between the neuronal COX-2 expression in the cerebrum, the formation of tau- and alpha-synuclein-negative but ubiquitin-positive neuronal inclusions (UPIs), and dementia in motor neuron disease (MND), we examined neuronal COX-2 immunoreactivity in the frontal cortex and hippocampus of patients with non-demented ALS without UPIs ( n=11), ALSD with UPIs ( n=6), and normal controls ( n=24) using a quantitative immunohistochemical technique. Neuronal COX-2 expression in all CA1-4 in the hippocampus was significantly up-regulated in the ALSD group, and, to lesser degree but significantly, in the ALS group. Neuronal COX-2 expression in the frontal cortex was also significantly up-regulated in the ALSD group but not in the ALS group. These findings suggest that (1) the frontal cortex and hippocampus of MND are involved in the same pathogenic process associated with COX-2 induction that has been observed in spinal anterior horn cells, (2) COX-2 induction in the cerebrum is a pathogenic process that can occur even in the absence of UPI formation in MND, and (3) COX-2 expression in the cerebrum may be associated with cognitive dysfunction in MND.


Assuntos
Esclerose Lateral Amiotrófica/enzimologia , Demência/enzimologia , Hipocampo/patologia , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintases/metabolismo , Regulação para Cima , Idoso , Peptídeos beta-Amiloides/metabolismo , Esclerose Lateral Amiotrófica/complicações , Contagem de Células/métodos , Ciclo-Oxigenase 2 , Demência/etiologia , Feminino , Lobo Frontal/citologia , Lobo Frontal/metabolismo , Regulação da Expressão Gênica , Hipocampo/enzimologia , Humanos , Imuno-Histoquímica/métodos , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Fragmentos de Peptídeos/metabolismo , Mudanças Depois da Morte , Ubiquitina/metabolismo
13.
Acta Neuropathol ; 106(4): 348-56, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-12883830

RESUMO

We describe three cases of early- (cases 1-3, 28-39 years) and one of late-onset (case 4, 76 years) Alzheimer's disease (AD) with 'cotton wool' plaques (CWPs) but without a family history indicating autosomal dominant inheritance. The early-onset cases, but not the late-onset case, showed remarkable aggression, disinhibition, and impulsiveness. Spastic paraparesis was observed in only one early-onset case. Hematoxylin-eosin-stained sections showed numerous CWPs, especially in the temporal cortex, in all cases. Bielschowsky-stained sections showed neurofibrillary tangles and minor neuritic changes surrounding the CWPs in three cases, but not in case 2. Gallyas-Braak-stained sections showed weak argyrophilia in homogeneous material of the CWPs in cases 2 and 4. Quantitative analysis demonstrated that Abeta42 was deposited more predominantly than Abeta40 in three cases. However, in case 2, approximately twice as much Abeta40 as Abeta42 was deposited. Tau immunostaining demonstrated neuritic changes in three cases, but not in case 2. alpha-Synuclein-positive Lewy bodies (LBs) and astrocytic lesions containing non-Abeta component of AD amyloid (NAC), a central fragment of alpha-synuclein, were found in case 3. In conclusion, (1) a frontal lobe syndrome-like personality change may be one of the characteristic clinical features of early-onset CWP-AD, (2) the deposition pattern of Abeta40 and Abeta42 in CWP-AD is more variable than that of presenilin-1-linked cases, (3) Abeta deposition can result in development of dementia without tau pathology, and (4) CWP-AD with LBs and several other neurodegenerative disorders with LBs share a common process involving alpha-synuclein and NAC deposition.


Assuntos
Doença de Alzheimer/metabolismo , Emaranhados Neurofibrilares/metabolismo , Adulto , Idade de Início , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/genética , Peptídeos beta-Amiloides/metabolismo , Autopsia/métodos , Encéfalo/anatomia & histologia , Encéfalo/metabolismo , Encéfalo/patologia , Estudos de Casos e Controles , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Proteínas do Tecido Nervoso/metabolismo , Emaranhados Neurofibrilares/genética , Exame Neurológico , Príons/metabolismo , Coloração e Rotulagem , Sinucleínas , alfa-Sinucleína , Proteínas tau/metabolismo
14.
Neurol Res ; 25(5): 533-7, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12866204

RESUMO

A 66-year-old man had suffered from a slow and steady decline in both physical and cognitive function for four years. He showed bradykinesia and small step gait with supranuclear vertical gaze palsy, especially upward gaze palsy. He was started on levodopa therapy but without response. A diagnosis of progressive supranuclear palsy was clinically suspected. He died at age 69. Pathologically, many alpha-synuclein positive inclusions were detected both in the brain stem and cerebral cortices, and the diagnosis of dementia with Lewy bodies was made. Scattered alpha-synuclein-positive inclusions and threads, which may be a pathological substrate for supranuclear gaze palsy, were identified in the rostal midbrain. From a review of five cases of dementia with Lewy bodies with supranuclear gaze palsy including this case, the absence of falls in the early stage of the disease, fluctuation of cognition, hallucination and vertical gaze palsy with a more severe defect in the upward direction distinguished dementia with Lewy bodies with vertical gaze palsy from progressive supranuclear palsy. In the differential diagnosis of parkinsonism with gaze palsy, clinicians should consider dementia with Lewy bodies with gaze palsy as well as progressive supranuclear palsy.


Assuntos
Doença por Corpos de Lewy/patologia , Paralisia Supranuclear Progressiva/patologia , Encéfalo/patologia , Diagnóstico Diferencial , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade
15.
Neurosci Lett ; 343(3): 175-9, 2003 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-12770691

RESUMO

We examined neuronal expression of cyclooxygenase-2, a pro-inflammatory protein, and neuron densities in the CA1-4 of the hippocampus in three cases of Alzheimer's disease with cotton wool plaques (CWP-AD), 17 cases of typical Alzheimer's disease without CWPs (tAD), and 26 normal controls. Cyclooxygenase-2 expression was significantly increased in all of the CA1-4 in tAD, but not in any subdivision in CWP-AD, compared with controls. Cyclooxygenase-2 expression in tAD was also significantly up-regulated compared with that in CWP-AD in all subdivisions. Furthermore, neuron density in the hippocampus was not significantly reduced in CWP-AD cases compared with controls despite remarkable intra- and extraneuronal Abeta deposition. These findings suggest that unknown factors besides Abeta deposition are necessary for the cyclooxygenase-2 up-regulation and neurodegeneration in Alzheimer's disease.


Assuntos
Doença de Alzheimer/enzimologia , Doença de Alzheimer/genética , Encéfalo/patologia , Hipocampo/enzimologia , Isoenzimas/biossíntese , Prostaglandina-Endoperóxido Sintases/biossíntese , Regulação para Cima/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/patologia , Contagem de Células , Ciclo-Oxigenase 2 , Feminino , Humanos , Imuno-Histoquímica , Isoenzimas/genética , Masculino , Proteínas de Membrana , Pessoa de Meia-Idade , Prostaglandina-Endoperóxido Sintases/genética , Células Piramidais/enzimologia , Lobo Temporal/patologia
16.
Acta Neuropathol ; 105(3): 259-64, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12557013

RESUMO

Fahr-type calcification is a relatively common finding in the elderly, and in younger patients with Alzheimer's disease, calcification in the basal ganglia is not uncommon. However, as far as we know, an immunohistochemical study of intracranial calcification in neurodegenerative diseases has not been performed. In this study, we examined intracranial calcification of the basal ganglia and cerebellum with antibodies against noncollagenous bone matrix proteins. Nineteen brains were employed. The diagnoses were diffuse neurofibrillary tangles with calcification in five, Alzheimer's disease in five, Pick's disease in one, progressive supranuclear palsy in one, Parkinson's disease in one, and six controls. By conventional histology, three patterns of calcium (Ca) deposition were recognized: diffuse deposition within the tunica media of small and medium-sized vessels (type 1 deposition), free spherical or lobulated concretions (type 2 deposition) in the parenchyma, and rows of small calcospherites lying along capillaries (type 3 deposition). Type 3 deposition is relatively rare, and may be a hallmark of severe intracranial calcification. Immunohistochemistry demonstrated that osteopontin was present diffusely in all Ca deposition types. Osteocalcin was present chiefly in the peripheral region of type 2 and 3 depositions, as well as in only the rims of type 1 deposition. Bone sialoprotein and osteonectin were found only in the core portions of type 2 and 3 depositions. In brief, type 1 deposition shows a different staining pattern from type 2 and 3. Different Ca deposition patterns of noncollagenous bone matrix proteins may suggest their separate roles in the pathogenesis of intracranial calcification.


Assuntos
Gânglios da Base/patologia , Calcinose/patologia , Cerebelo/patologia , Doenças Neurodegenerativas/patologia , Idoso , Idoso de 80 Anos ou mais , Gânglios da Base/metabolismo , Cerebelo/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Sialoproteína de Ligação à Integrina , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/metabolismo , Osteocalcina/metabolismo , Osteonectina/metabolismo , Osteopontina , Sialoglicoproteínas/metabolismo
17.
Acta Neuropathol ; 105(2): 163-9, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12536227

RESUMO

Diffuse Lewy body disease (DLBD) is characterized by the presence of Lewy bodies (LB) in the neurons and neurites of cortical, subcortical, and brain stem structures. Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB. In DLBD, abnormal accumulation of alphaS has been reported in both neurons and glia, but studies on glial lesions in DLBD have been limited. We examined in detail the constituents and distribution of glial lesions in eight patients with DLBD and report the pathogenesis of the glial lesions. alphaS-positive neuronal cytoplasmic inclusions (NI), neuropil threads (NT), and coiled bodies (CB) showed similar immunostaining profiles. Without pretreatment, NI, NT, and CB were detected by all antibodies against alphaS. The immunostaining profile of star-like astrocytes (SLA) was quite different from those of NI, NT, and CB. A few SLA were stained by an antibody against the non-Abeta component portion of alphaS without pretreatment, but formic acid pretreatment dramatically enhanced SLA immunoreactivity. SLA and CB were found in all eight brains with DLBD. SLA were scarce in the brain stem, but there were hundreds of SLA per visual field at x100 magnification in the temporal cortex of most cases, while CB were found diffusely in both the cerebral cortex and brain stem, similar to NI. This suggests that the pathogenesis of SLA is different from those of NI and CB.


Assuntos
Encéfalo/patologia , Doença por Corpos de Lewy/patologia , Neuroglia/patologia , Idoso , Idoso de 80 Anos ou mais , Astrócitos/metabolismo , Astrócitos/patologia , Astrócitos/ultraestrutura , Encéfalo/metabolismo , Encéfalo/ultraestrutura , Corpos Enovelados/metabolismo , Corpos Enovelados/patologia , Corpos Enovelados/ultraestrutura , Feminino , Humanos , Imuno-Histoquímica , Corpos de Inclusão/metabolismo , Corpos de Inclusão/patologia , Corpos de Inclusão/ultraestrutura , Corpos de Lewy/metabolismo , Corpos de Lewy/patologia , Corpos de Lewy/ultraestrutura , Doença por Corpos de Lewy/metabolismo , Masculino , Microscopia Confocal , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Neuroglia/metabolismo , Neuroglia/ultraestrutura , Neurônios/metabolismo , Neurônios/patologia , Neurônios/ultraestrutura , Filamentos do Neurópilo/metabolismo , Filamentos do Neurópilo/patologia , Filamentos do Neurópilo/ultraestrutura , Sinucleínas , alfa-Sinucleína
18.
Acta Neuropathol ; 104(6): 637-48, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12410385

RESUMO

Approximately 60% of familial and sporadic Alzheimer's disease (AD) cases manifest Lewy bodies (LBs), of which a major component is alpha-synuclein. Although the pathogenic role of alpha-synuclein in AD remains unclear, LB formation might be associated with pathological beta-amyloid (Abeta) overproduction. Here, we present the clinical and pathological characteristics of two affected family members from a pedigree with the E184D mutation of presenilin-1. One case presented with typical clinical features of AD, but the other case also developed clinical characteristics of dementia with Lewy bodies (DLB), including visual hallucinations, delusions, and parkinsonism. In both cases, neuropathological examination revealed numerous neurofibrillary tangles and severe Abeta deposition in senile plaques and amyloid angiopathy, in which Abeta42 rather than Abeta40 was predominant. Furthermore, remarkable alpha-synuclein pathology, including LBs and the accumulation of the non-Abeta component of AD amyloid (NAC) in plaques and astrocytes, was detected only in the case that presented with the symptoms of DLB. These findings suggest that (1) LB pathology can influence the clinical features of familial AD, (2) the E184D mutation of presenilin-1 may be associated with the LB formation through Abeta overproduction, although the process of LB formation is strongly affected by other unknown mechanisms, (3) in neurodegenerative disorders with LBs, there is a common pathophysiological background inducing NAC accumulation in neuritic plaques and astrocytes, and (4) the NAC accumulation in neuritic plaques is modulated by the abnormally aggregated tau protein.


Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/análise , Peptídeos beta-Amiloides/genética , Amiloide/análise , Amiloide/genética , Proteínas de Membrana/análise , Proteínas de Membrana/genética , Mutação de Sentido Incorreto/genética , Proteínas do Tecido Nervoso/análise , Proteínas do Tecido Nervoso/genética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Presenilina-1 , Sinucleínas , alfa-Sinucleína
19.
Int J Geriatr Psychiatry ; 17(9): 851-8, 2002 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12221660

RESUMO

OBJECTIVES: The purpose of this study was the development of the quality of life (QOL) questionnaire for dementia (QOL-D) in Japan. METHODS: We performed a questionnaire survey of QOL assessment in elderly patients with dementia in Japan, and developed QOL-D. RESULTS: The final version consists of only 31 items grouped into six response sets, each with its own scale. Reliability is good to excellent, and validity is, to some extent, established. The six domains of health-related QOL are divided into two groups. One is the positive and the other is the negative aspects of health-related QOL. The positive aspects have been shown to correlate positively with cognitive function and activities of daily living (ADL) score, whereas the negative aspects have not. The concept of QOL for elderly patients with dementia in Japan is similar to that in Western countries. CONCLUSION: We demonstrated that QOL-D is a reliable and valid instrument for QOL assessment in elderly patients with dementia in Japan.


Assuntos
Demência/diagnóstico , Nível de Saúde , Qualidade de Vida , Inquéritos e Questionários , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Demência/epidemiologia , Análise Fatorial , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Reprodutibilidade dos Testes
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